Prostate cancer is the most common cancer in US males, with an estimated 313,780 new cases and 35,770 deaths in 2025.¹ Several treatment options are available for localized prostate cancer that have similar outcomes, including active surveillance for low-risk cancers, surgery, or radiotherapy.^2,3 Conventional fractionation radiotherapy (CFRT) with 40 to 45 fractions over 8 to 9 weeks has been used for decades. Over the past 2 decades, moderate hypofractionation schedules with 2.4 to 3.4 Gy per fraction over 20 to 28 fractions have become standard, as many noninferiority randomized clinical trials (RCTs) such as CHHiP (UK),⁴ PROFIT (Canada and Europe),⁵ NRG Oncology RTOG 0415 (US),⁶ HYPRO (Netherlands),^7,8 and HYPO-RT-PC (Sweden and Denmark),⁹ have shown the noninferiority of moderately hypofractionated radiotherapy compared with CFRT. Notably, most of these noninferiority studies primarily included patients with low- or intermediate-risk prostate cancer, except for the HYPO-RT-PC trial,⁹ which also included patients with intermediate- and high-risk prostate cancer.

These noninferiority studies, along with technological advances in radiotherapy, such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and image-guided radiotherapy (IGRT), paved the path to ultrahypofractionated stereotactic body radiotherapy (SBRT) that is delivered in 5 fractions of ≥ 6 Gy. This high dose per fraction may have a radiobiologic advantage over conventional fractionation. The relatively low a/ß ratio of prostate cancer, estimated to be between 1 and 2, suggests that tumor cells may be particularly sensitive to the high doses per fraction delivered in SBRT.^10-13 Compared with CFRT, SBRT-induced tumor cell death may also be mediated through different pathways; this pathway appears to be generated in a dose-dependent manner, particularly with doses > 8 Gy per fraction.^14,15 Additionally, the higher a/ß ratio for the surrounding organs at risk, such as the bladder and rectum, theoretically allows for an improved therapeutic ratio window that maximizes tumor control while minimizing damage to healthy tissues.

A substantial body of evidence from prospective studies and meta-analyses supports the use of SBRT for localized prostate cancer. HYPO-RT-PC, a significant phase 3 noninferiority study, enrolled 1200 patients with intermediate (89%) and high-risk (11%) prostate cancer randomized between 2 arms, including CFRT to 78 Gy in 39 fractions and SBRT to 42.7 Gy in 7 fractions, treated 3 days weekly. After a median follow-up of 60 months, the estimated 5-year biochemical relapse-free survival rate was 84% in both groups.⁹ This trial was notable because it was the first randomized study to demonstrate that SBRT was noninferior to CFRT in intermediate- and high-risk prostate cancer patients. Another pivotal phase 3 trial, the PACE-B study, enrolled 874 patients to compare SBRT (36.25 Gy to the prostate gland, with a secondary dose of 40 Gy to the gross tumor volume where applicable, in 5 fractions) with CFRT (78 Gy in 39 fractions) and moderately hypofractionated radiotherapy (HFRT) (62 Gy in 20 fractions) in patients with low- or intermediate-risk prostate cancer. With a 74-month median follow-up, the study reported 5-year biochemical free rates of 94.6% for CFRT and 95.8% for SBRT, confirming the noninferiority of SBRT to CFRT.¹⁵

SBRT offers short, effective, and convenient treatment to many patients with localized prostate cancer. While previous guidelines were more restrictive, the March 2026 National Comprehensive Cancer Network (NCCN) guidelines now list SBRT as a preferred treatment modality for high-risk prostate cancer.¹⁶

Given the growing body of evidence supporting the efficacy and safety of SBRT, we implemented an SBRT program in 2014 at a tertiary care center for veterans. This retrospective study was undertaken to evaluate the early efficacy and toxicity of SBRT in patients with localized prostate cancer treated at our institution, including patients across all risk stratifications.

METHODS

We identified 242 patients diagnosed with prostate cancer who underwent SBRT treatment between November 2014 and October 2024 at Overland Park Veterans Affairs Radiation Oncology Clinic. For the final analysis, 46 patients with < 2 years of follow-up and 22 patients who died from causes other than prostate cancer were excluded, resulting in a cohort of 174 patients with ≥ 24-month follow-up.

Treatment

Patients eligible for staging underwent imaging according to NCCN guidelines, including computed tomography (CT) of the abdomen and pelvis, bone scintigraphy, or, in recent years, prostate-specific membrane antigen positron emission tomography, primarily used for unfavorable intermediate-risk (UIR) and high-risk (HR) cancers. Patients with a negative staging work-up for nodal or skeletal disease were included. Prior to planning the CT simulation, patients were given bowel preparation instructions, including a low-fiber and low-gas-producing diet, simethicone, and enemas, the night before and morning of the simulation. Patients were instructed to arrive with a comfortably full bladder, having not voided for 2 to 3 hours prior to the procedure. At Kansas City Veterans Affairs Medical Center (KCVAMC), SBRT treatment was generally restricted to patients with a baseline American Urological Association symptom score of 15 to 20 out of 35 and a prostate gland size < 80 mL to minimize the risk of acute urinary toxicity. We did not use intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast agents for planning CT simulation.

Patients were placed in a supine position, and a vacuum bag was used for immobilization. Following the CT simulation, the images were transferred to the Eclipse treatment planning system. The clinical target volume (CTV) encompassed the prostate and the proximal 1.0 cm of the seminal vesicles for Gleason score (GS) 1 to 2, and the entire seminal vesicle was included for GS 3 to 5, which is consistent with KCVAMC practice and established safety protocols. The planning target volume (PTV) was created by uniformly expanding the CTV by 5 to 7 mm, except for the posterior margin, which was limited to 3 to 5 mm. When elective nodal radiotherapy was planned for HR prostate cancer, the pelvic field for CT simulation started at the L-2 upper border, with the lower border extending to the lesser trochanter. The pelvic nodes were delineated per Radiation Therapy Oncology Group (RTOG) guidelines.¹⁷ The CTV nodes (CTVn), including common iliac, external and internal iliac nodes, obturator, and presacral nodes, were created by uniformly expanding the CTVn by 2 to 3 mm. Slice-by-slice corrections were made to avoid bowel overlap in these patients.

The use of androgen deprivation therapy (ADT) for a duration of 6 to 24 months was prescribed for patients with UIR or HR prostate cancer per NCCN guidelines.¹⁶ The prescribed dose to the PTV was 36.25 to 40 Gy (40 Gy was mostly used as a boost to the dominant lesion) in 5 fractions, with each fraction ranging from 7.25 to 8 Gy. For elective nodal radiotherapy in patients at HR, the prescribed dose was 25 Gy in 5 fractions. All patients were planned for VMAT, which aims to deliver ≥ 95% of the prescription dose to 95% of the PTV. Once the physician approved the treatment plan and physics quality assessment was completed, treatments commenced on an every-other-day schedule. Patients received the same bowel preparation instructions for each treatment as for the planning CT simulation. Daily treatment accuracy was confirmed via daily 3-dimensional cone-beam CT (CBCT) for IGRT. No fiducials or hydrogel rectal spacers were used.

Follow-up Schedule and Toxicity Assessment

Follow-up assessments were conducted 4 to 6 weeks after radiation therapy and then repeated every 6 months for 2 to 5 years, and annually thereafter. At each follow-up visit, patients were evaluated for genitourinary (GU) and gastrointestinal (GI) toxicity, according to RTOG toxicity criteria. Prostate-specific antigen (PSA) levels were monitored; in patients receiving ADT, testosterone levels were also checked.

Statistical Analysis

Biochemical failure was defined using the Phoenix definition (nadir PSA + 2 ng/mL). Differences between dose cohorts were assessed using the log-rank test for survival outcomes and X² testing for categorical variables. GU and GI toxicities were summarized as cumulative incidences of RTOG grade ≥ II events. Statistical significance was set at P < .05.

RESULTS

One hundred seventy-four patients were included in the retrospective review. Patients had a median follow-up of 45 months (range, 24-111) (Figure). The median age at treatment was 74 years (range, 51-88), and the median pretreatment PSA level was 11.9 ng/mL (range, 0.6-69.5). Twenty-six patients (14.9%) had a GS 1, 77 (44.3%) had GS 2, 41 (23.6%) had GS 3, 18 (10.3%) had GS 4, and 12 (6.9%) had GS 5. Fifty-one patients (29.3%) received elective pelvic nodal radiotherapy, and 93 patients (53.4%) received ADT (Table 1).

At 24 months follow-up, 6 patients (3.4%) had biochemical failures. One patient died from metastatic prostate cancer, and 5 patients are living with biochemical failure (Table 2). The actuarial 5-year overall survival (OS) rate was 99.4%, and the 5-year disease-free survival (DFS) rate was 96.6%. We performed a subanalysis comparing outcomes of the 36.25 Gy vs 40 Gy SBRT cohorts. There was no statistically significant difference in DFS, OS, or the cumulative incidence of grade II/III toxicity between patients treated with 40 Gy vs 36.25 Gy. Outcomes stratified by NCCN risk groups (low, intermediate, high/very high) are detailed in Table 3. As expected, DFS was slightly lower in the high-risk group, but overall disease control remained high across all stratifications.

The cumulative incidence of RTOG grade II and higher GU toxicity was 28.2% (Table 4). This included 46 patients (26.4%) with grade II GU toxicity and 2 patients (1.2%) who developed grade III GU complications (1 requiring self-catheterization and another a suprapubic catheter for urinary retention). One patient (0.6%) treated with a 40 Gy dose regimen experienced a grade IV GU complication in the form of a rectovesical fistula necessitating surgical intervention.

The cumulative incidence of RTOG grade II or higher GI toxicity was 3.4%, and no grade III or IV gastrointestinal toxicities were observed during the follow-up period. Importantly, intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast were not routinely used in this cohort of patients.

The high rates of actuarial 5-year DFS and OS observed suggest a favorable initial response to the SBRT regimen employed at KCVAMC. However, given the potential for late recurrence in patients with prostate cancer, longer follow-up is essential to determine the durability of these outcomes. The observed GU toxicity rate of 28.2% for grade II and higher events warrants careful consideration and compares with other published data on SBRT for prostate cancer.¹⁵ The occurrence of a grade IV rectovesical fistula, although rare, is a notable adverse event that warrants discussion in the context of the treatment approach. The low incidence of grade II or higher GI toxicity is an encouraging finding, particularly given that hydrogel rectal spacers are not routinely used to minimize rectal exposure.

DISCUSSION

The primary objective of this retrospective study was to evaluate the outcomes of SBRT for patients with localized prostate cancer treated at KCVAMC and to compare these results with those reported in the literature. Our findings demonstrate promising intermediate-term efficacy, with an estimated 5-year DFS of 96.6% and OS of 99.4% at a median follow-up of 45 months. Furthermore, the observed toxicity profile appears acceptable, with a cumulative grade II and higher GU toxicity rate of 28.2% and a grade II or higher GI toxicity rate of 3.4%. Notably, these outcomes were achieved without the routine use of intraprostatic fiducials or hydrogel rectal spacers.

Two pivotal randomized phase 3 trials have established the noninferiority of ultrahypofractionated radiotherapy (UHRT) with SBRT over conventional fractionation. The HYPO-RT-PC trial compared SBRT (42.7 Gy in 7 fractions) with conventional fractionation (78 Gy in 39 fractions) in intermediate- and high-risk patients with prostate cancer and reported a 5-year biochemical relapse-free survival of 84% in both arms.⁹ The PACE-B trial, which included patients at low- and intermediate-risk, compared SBRT (36.25 Gy in 5 fractions) with conventional or moderate HFRT and reported a 5-year biochemical control rate of 95.8% in the SBRT arm and 94.6% in the control arm.¹⁵

A comprehensive review and meta-analysis of 7 phase 3 studies involving 6795 patients compared different radiotherapy regimens, namely, UHRT, HFRT, and CFRT, and reported that after 5 years, the DFS rates were 85.1% for CFRT, 86% for HFRT, and 85% for UHRT, with no significant difference in toxicity among the 3 different treatment approaches.¹⁸ This suggests that shorter, more intense radiotherapy schedules (UHRT and HFRT) may be as effective and safe as traditional, longer courses of radiation.

There are multiple published nonrandomized prospective trials in which thousands of patients with extreme hypofractionation have been treated with different doses, fractions, and techniques. While heterogeneity and limited long-term follow-up in the existing evidence are acknowledged, these data suggest that prostate SBRT provides appropriate biochemical control with few high-grade toxicities, supporting its ongoing global use and justifying further prospective investigations. Comparative data are shown in Table 5. Several ongoing studies are evaluating noninferiority, superiority, and cost-effectiveness using different methodologies (Table 6).^9,15,19-24

This study’s efficacy outcomes, particularly the high DFS rate, are consistent with the findings from these landmark trials, suggesting that the SBRT regimen used at KCVAMC is effective in achieving early disease control despite 17.2% of patients having high-risk disease. The GU toxicity observed in this study, with a 28.2% rate of grade II or higher events, is also comparable with the 26.9% reported in the 5-fraction SBRT arm of the PACE-B trial, which had a longer median follow-up of 74 months.¹⁵ It is important to note that a portion of these grade II events occurred in patients who were already on a blockers for pre-existing lower urinary tract symptoms before starting radiotherapy, which may inflate the observed cumulative acute toxicity score.

A critical comparison is how SBRT toxicity aligns with moderate hypofractionation (eg, 60 Gy in 20 fractions or 70 Gy in 28 fractions as reported by others).^4,6 Our observed grade III and higher GU toxicity rate (1.7%) and grade III and higher GI toxicity rate (0%) are highly favorable when compared with historical moderate hypofractionation data, which typically report grade III GU toxicity in the range of 2% to 3% and grade III GI toxicity around 1% to 2%. This suggests that despite the higher dose per fraction, SBRT does not necessarily lead to increased severe acute toxicity, potentially offering a superior therapeutic ratio for GI and GU sparing.

However, the occurrence of a grade IV rectovesical fistula in 1 patient (0.6%)—who received the 40 Gy dose—was a serious complication that warrants careful consideration. This rare, but severe, complication in the higher dose cohort underscores the potential for increased organ-at-risk toxicity, particularly in the absence of a hydrogel rectal spacer, which is designed to mitigate high-dose rectal exposure. While the overall rate of significant GU toxicity remains low, this event highlights the potential risks associated with SBRT. Hydrogel rectal spacers are designed to increase the distance between the prostate and the rectum, which can reduce the rectal radiation dose and potentially mitigate the risk of such fistulas. The low rate of grade II or worse GI toxicity (3.4%) in our study is noteworthy, especially considering that hydrogel spacers were not routinely used. This finding aligns with the 2.5% GI toxicity rate reported in the SBRT arm of the PACE-B trial, suggesting that careful treatment planning and delivery techniques, such as VMAT-IMRT and daily CBCT for IGRT, may contribute to minimizing GI toxicity even without the use of rectal spacers.¹⁵ The exclusive use of 3-dimensional CBCT for IGRT in our study, without the use of fiducial markers, suggests that accurate target localization can be achieved with this approach, contributing to the observed efficacy and reduced toxicity.

Strengths and Limitations

This study’s retrospective, single-center design may have introduced selection bias. The median follow-up of 45 months, while substantial, is still relatively short for assessing very late toxicities and long-term oncologic outcomes in prostate cancer, which is known for late recurrences. Additionally, the lack of a direct comparison group within KCVAMC limits the ability to definitively attribute the observed outcomes solely to SBRT treatment. However, the strengths of this study include the inclusion of a consecutive series of veteran patients with localized prostate cancer across all risk categories, providing a real-world perspective on SBRT outcomes in a diverse patient population. Furthermore, the detailed assessment of efficacy and toxicity via standardized RTOG criteria enhances the comparability of our findings with those of other published prospective studies, despite the retrospective nature of the data.

CONCLUSIONS

This single-institution retrospective analysis revealed that short-term SBRT (36.25 to 40 Gy in 5 fractions), with a minimum follow-up of 24 months and a median follow-up of 45 months, for localized prostate cancer, including patients at HR, is associated with promising early efficacy and acceptable toxicity, even in the absence of routine fiducial or hydrogel spacer use. The favorable actuarial 5-year DFS and OS rates, coupled with a manageable toxicity profile, suggest that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer. However, a longer follow-up is necessary to confirm these findings and fully characterize the long-term efficacy and toxicity of this SBRT regimen. Nevertheless, the results contribute to the growing body of evidence suggesting that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer.

Prostate cancer is the most common cancer in US males, with an estimated 313,780 new cases and 35,770 deaths in 2025.¹ Several treatment options are available for localized prostate cancer that have similar outcomes, including active surveillance for low-risk cancers, surgery, or radiotherapy.^2,3 Conventional fractionation radiotherapy (CFRT) with 40 to 45 fractions over 8 to 9 weeks has been used for decades. Over the past 2 decades, moderate hypofractionation schedules with 2.4 to 3.4 Gy per fraction over 20 to 28 fractions have become standard, as many noninferiority randomized clinical trials (RCTs) such as CHHiP (UK),⁴ PROFIT (Canada and Europe),⁵ NRG Oncology RTOG 0415 (US),⁶ HYPRO (Netherlands),^7,8 and HYPO-RT-PC (Sweden and Denmark),⁹ have shown the noninferiority of moderately hypofractionated radiotherapy compared with CFRT. Notably, most of these noninferiority studies primarily included patients with low- or intermediate-risk prostate cancer, except for the HYPO-RT-PC trial,⁹ which also included patients with intermediate- and high-risk prostate cancer.

These noninferiority studies, along with technological advances in radiotherapy, such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and image-guided radiotherapy (IGRT), paved the path to ultrahypofractionated stereotactic body radiotherapy (SBRT) that is delivered in 5 fractions of ≥ 6 Gy. This high dose per fraction may have a radiobiologic advantage over conventional fractionation. The relatively low a/ß ratio of prostate cancer, estimated to be between 1 and 2, suggests that tumor cells may be particularly sensitive to the high doses per fraction delivered in SBRT.^10-13 Compared with CFRT, SBRT-induced tumor cell death may also be mediated through different pathways; this pathway appears to be generated in a dose-dependent manner, particularly with doses > 8 Gy per fraction.^14,15 Additionally, the higher a/ß ratio for the surrounding organs at risk, such as the bladder and rectum, theoretically allows for an improved therapeutic ratio window that maximizes tumor control while minimizing damage to healthy tissues.

A substantial body of evidence from prospective studies and meta-analyses supports the use of SBRT for localized prostate cancer. HYPO-RT-PC, a significant phase 3 noninferiority study, enrolled 1200 patients with intermediate (89%) and high-risk (11%) prostate cancer randomized between 2 arms, including CFRT to 78 Gy in 39 fractions and SBRT to 42.7 Gy in 7 fractions, treated 3 days weekly. After a median follow-up of 60 months, the estimated 5-year biochemical relapse-free survival rate was 84% in both groups.⁹ This trial was notable because it was the first randomized study to demonstrate that SBRT was noninferior to CFRT in intermediate- and high-risk prostate cancer patients. Another pivotal phase 3 trial, the PACE-B study, enrolled 874 patients to compare SBRT (36.25 Gy to the prostate gland, with a secondary dose of 40 Gy to the gross tumor volume where applicable, in 5 fractions) with CFRT (78 Gy in 39 fractions) and moderately hypofractionated radiotherapy (HFRT) (62 Gy in 20 fractions) in patients with low- or intermediate-risk prostate cancer. With a 74-month median follow-up, the study reported 5-year biochemical free rates of 94.6% for CFRT and 95.8% for SBRT, confirming the noninferiority of SBRT to CFRT.¹⁵

SBRT offers short, effective, and convenient treatment to many patients with localized prostate cancer. While previous guidelines were more restrictive, the March 2026 National Comprehensive Cancer Network (NCCN) guidelines now list SBRT as a preferred treatment modality for high-risk prostate cancer.¹⁶

Given the growing body of evidence supporting the efficacy and safety of SBRT, we implemented an SBRT program in 2014 at a tertiary care center for veterans. This retrospective study was undertaken to evaluate the early efficacy and toxicity of SBRT in patients with localized prostate cancer treated at our institution, including patients across all risk stratifications.

METHODS

We identified 242 patients diagnosed with prostate cancer who underwent SBRT treatment between November 2014 and October 2024 at Overland Park Veterans Affairs Radiation Oncology Clinic. For the final analysis, 46 patients with < 2 years of follow-up and 22 patients who died from causes other than prostate cancer were excluded, resulting in a cohort of 174 patients with ≥ 24-month follow-up.

Treatment

Patients eligible for staging underwent imaging according to NCCN guidelines, including computed tomography (CT) of the abdomen and pelvis, bone scintigraphy, or, in recent years, prostate-specific membrane antigen positron emission tomography, primarily used for unfavorable intermediate-risk (UIR) and high-risk (HR) cancers. Patients with a negative staging work-up for nodal or skeletal disease were included. Prior to planning the CT simulation, patients were given bowel preparation instructions, including a low-fiber and low-gas-producing diet, simethicone, and enemas, the night before and morning of the simulation. Patients were instructed to arrive with a comfortably full bladder, having not voided for 2 to 3 hours prior to the procedure. At Kansas City Veterans Affairs Medical Center (KCVAMC), SBRT treatment was generally restricted to patients with a baseline American Urological Association symptom score of 15 to 20 out of 35 and a prostate gland size < 80 mL to minimize the risk of acute urinary toxicity. We did not use intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast agents for planning CT simulation.

Patients were placed in a supine position, and a vacuum bag was used for immobilization. Following the CT simulation, the images were transferred to the Eclipse treatment planning system. The clinical target volume (CTV) encompassed the prostate and the proximal 1.0 cm of the seminal vesicles for Gleason score (GS) 1 to 2, and the entire seminal vesicle was included for GS 3 to 5, which is consistent with KCVAMC practice and established safety protocols. The planning target volume (PTV) was created by uniformly expanding the CTV by 5 to 7 mm, except for the posterior margin, which was limited to 3 to 5 mm. When elective nodal radiotherapy was planned for HR prostate cancer, the pelvic field for CT simulation started at the L-2 upper border, with the lower border extending to the lesser trochanter. The pelvic nodes were delineated per Radiation Therapy Oncology Group (RTOG) guidelines.¹⁷ The CTV nodes (CTVn), including common iliac, external and internal iliac nodes, obturator, and presacral nodes, were created by uniformly expanding the CTVn by 2 to 3 mm. Slice-by-slice corrections were made to avoid bowel overlap in these patients.

The use of androgen deprivation therapy (ADT) for a duration of 6 to 24 months was prescribed for patients with UIR or HR prostate cancer per NCCN guidelines.¹⁶ The prescribed dose to the PTV was 36.25 to 40 Gy (40 Gy was mostly used as a boost to the dominant lesion) in 5 fractions, with each fraction ranging from 7.25 to 8 Gy. For elective nodal radiotherapy in patients at HR, the prescribed dose was 25 Gy in 5 fractions. All patients were planned for VMAT, which aims to deliver ≥ 95% of the prescription dose to 95% of the PTV. Once the physician approved the treatment plan and physics quality assessment was completed, treatments commenced on an every-other-day schedule. Patients received the same bowel preparation instructions for each treatment as for the planning CT simulation. Daily treatment accuracy was confirmed via daily 3-dimensional cone-beam CT (CBCT) for IGRT. No fiducials or hydrogel rectal spacers were used.

Follow-up Schedule and Toxicity Assessment

Follow-up assessments were conducted 4 to 6 weeks after radiation therapy and then repeated every 6 months for 2 to 5 years, and annually thereafter. At each follow-up visit, patients were evaluated for genitourinary (GU) and gastrointestinal (GI) toxicity, according to RTOG toxicity criteria. Prostate-specific antigen (PSA) levels were monitored; in patients receiving ADT, testosterone levels were also checked.

Statistical Analysis

Biochemical failure was defined using the Phoenix definition (nadir PSA + 2 ng/mL). Differences between dose cohorts were assessed using the log-rank test for survival outcomes and X² testing for categorical variables. GU and GI toxicities were summarized as cumulative incidences of RTOG grade ≥ II events. Statistical significance was set at P < .05.

RESULTS

One hundred seventy-four patients were included in the retrospective review. Patients had a median follow-up of 45 months (range, 24-111) (Figure). The median age at treatment was 74 years (range, 51-88), and the median pretreatment PSA level was 11.9 ng/mL (range, 0.6-69.5). Twenty-six patients (14.9%) had a GS 1, 77 (44.3%) had GS 2, 41 (23.6%) had GS 3, 18 (10.3%) had GS 4, and 12 (6.9%) had GS 5. Fifty-one patients (29.3%) received elective pelvic nodal radiotherapy, and 93 patients (53.4%) received ADT (Table 1).

At 24 months follow-up, 6 patients (3.4%) had biochemical failures. One patient died from metastatic prostate cancer, and 5 patients are living with biochemical failure (Table 2). The actuarial 5-year overall survival (OS) rate was 99.4%, and the 5-year disease-free survival (DFS) rate was 96.6%. We performed a subanalysis comparing outcomes of the 36.25 Gy vs 40 Gy SBRT cohorts. There was no statistically significant difference in DFS, OS, or the cumulative incidence of grade II/III toxicity between patients treated with 40 Gy vs 36.25 Gy. Outcomes stratified by NCCN risk groups (low, intermediate, high/very high) are detailed in Table 3. As expected, DFS was slightly lower in the high-risk group, but overall disease control remained high across all stratifications.

The cumulative incidence of RTOG grade II and higher GU toxicity was 28.2% (Table 4). This included 46 patients (26.4%) with grade II GU toxicity and 2 patients (1.2%) who developed grade III GU complications (1 requiring self-catheterization and another a suprapubic catheter for urinary retention). One patient (0.6%) treated with a 40 Gy dose regimen experienced a grade IV GU complication in the form of a rectovesical fistula necessitating surgical intervention.

The cumulative incidence of RTOG grade II or higher GI toxicity was 3.4%, and no grade III or IV gastrointestinal toxicities were observed during the follow-up period. Importantly, intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast were not routinely used in this cohort of patients.

The high rates of actuarial 5-year DFS and OS observed suggest a favorable initial response to the SBRT regimen employed at KCVAMC. However, given the potential for late recurrence in patients with prostate cancer, longer follow-up is essential to determine the durability of these outcomes. The observed GU toxicity rate of 28.2% for grade II and higher events warrants careful consideration and compares with other published data on SBRT for prostate cancer.¹⁵ The occurrence of a grade IV rectovesical fistula, although rare, is a notable adverse event that warrants discussion in the context of the treatment approach. The low incidence of grade II or higher GI toxicity is an encouraging finding, particularly given that hydrogel rectal spacers are not routinely used to minimize rectal exposure.

DISCUSSION

The primary objective of this retrospective study was to evaluate the outcomes of SBRT for patients with localized prostate cancer treated at KCVAMC and to compare these results with those reported in the literature. Our findings demonstrate promising intermediate-term efficacy, with an estimated 5-year DFS of 96.6% and OS of 99.4% at a median follow-up of 45 months. Furthermore, the observed toxicity profile appears acceptable, with a cumulative grade II and higher GU toxicity rate of 28.2% and a grade II or higher GI toxicity rate of 3.4%. Notably, these outcomes were achieved without the routine use of intraprostatic fiducials or hydrogel rectal spacers.

Two pivotal randomized phase 3 trials have established the noninferiority of ultrahypofractionated radiotherapy (UHRT) with SBRT over conventional fractionation. The HYPO-RT-PC trial compared SBRT (42.7 Gy in 7 fractions) with conventional fractionation (78 Gy in 39 fractions) in intermediate- and high-risk patients with prostate cancer and reported a 5-year biochemical relapse-free survival of 84% in both arms.⁹ The PACE-B trial, which included patients at low- and intermediate-risk, compared SBRT (36.25 Gy in 5 fractions) with conventional or moderate HFRT and reported a 5-year biochemical control rate of 95.8% in the SBRT arm and 94.6% in the control arm.¹⁵

A comprehensive review and meta-analysis of 7 phase 3 studies involving 6795 patients compared different radiotherapy regimens, namely, UHRT, HFRT, and CFRT, and reported that after 5 years, the DFS rates were 85.1% for CFRT, 86% for HFRT, and 85% for UHRT, with no significant difference in toxicity among the 3 different treatment approaches.¹⁸ This suggests that shorter, more intense radiotherapy schedules (UHRT and HFRT) may be as effective and safe as traditional, longer courses of radiation.

There are multiple published nonrandomized prospective trials in which thousands of patients with extreme hypofractionation have been treated with different doses, fractions, and techniques. While heterogeneity and limited long-term follow-up in the existing evidence are acknowledged, these data suggest that prostate SBRT provides appropriate biochemical control with few high-grade toxicities, supporting its ongoing global use and justifying further prospective investigations. Comparative data are shown in Table 5. Several ongoing studies are evaluating noninferiority, superiority, and cost-effectiveness using different methodologies (Table 6).^9,15,19-24

This study’s efficacy outcomes, particularly the high DFS rate, are consistent with the findings from these landmark trials, suggesting that the SBRT regimen used at KCVAMC is effective in achieving early disease control despite 17.2% of patients having high-risk disease. The GU toxicity observed in this study, with a 28.2% rate of grade II or higher events, is also comparable with the 26.9% reported in the 5-fraction SBRT arm of the PACE-B trial, which had a longer median follow-up of 74 months.¹⁵ It is important to note that a portion of these grade II events occurred in patients who were already on a blockers for pre-existing lower urinary tract symptoms before starting radiotherapy, which may inflate the observed cumulative acute toxicity score.

A critical comparison is how SBRT toxicity aligns with moderate hypofractionation (eg, 60 Gy in 20 fractions or 70 Gy in 28 fractions as reported by others).^4,6 Our observed grade III and higher GU toxicity rate (1.7%) and grade III and higher GI toxicity rate (0%) are highly favorable when compared with historical moderate hypofractionation data, which typically report grade III GU toxicity in the range of 2% to 3% and grade III GI toxicity around 1% to 2%. This suggests that despite the higher dose per fraction, SBRT does not necessarily lead to increased severe acute toxicity, potentially offering a superior therapeutic ratio for GI and GU sparing.

However, the occurrence of a grade IV rectovesical fistula in 1 patient (0.6%)—who received the 40 Gy dose—was a serious complication that warrants careful consideration. This rare, but severe, complication in the higher dose cohort underscores the potential for increased organ-at-risk toxicity, particularly in the absence of a hydrogel rectal spacer, which is designed to mitigate high-dose rectal exposure. While the overall rate of significant GU toxicity remains low, this event highlights the potential risks associated with SBRT. Hydrogel rectal spacers are designed to increase the distance between the prostate and the rectum, which can reduce the rectal radiation dose and potentially mitigate the risk of such fistulas. The low rate of grade II or worse GI toxicity (3.4%) in our study is noteworthy, especially considering that hydrogel spacers were not routinely used. This finding aligns with the 2.5% GI toxicity rate reported in the SBRT arm of the PACE-B trial, suggesting that careful treatment planning and delivery techniques, such as VMAT-IMRT and daily CBCT for IGRT, may contribute to minimizing GI toxicity even without the use of rectal spacers.¹⁵ The exclusive use of 3-dimensional CBCT for IGRT in our study, without the use of fiducial markers, suggests that accurate target localization can be achieved with this approach, contributing to the observed efficacy and reduced toxicity.

Strengths and Limitations

This study’s retrospective, single-center design may have introduced selection bias. The median follow-up of 45 months, while substantial, is still relatively short for assessing very late toxicities and long-term oncologic outcomes in prostate cancer, which is known for late recurrences. Additionally, the lack of a direct comparison group within KCVAMC limits the ability to definitively attribute the observed outcomes solely to SBRT treatment. However, the strengths of this study include the inclusion of a consecutive series of veteran patients with localized prostate cancer across all risk categories, providing a real-world perspective on SBRT outcomes in a diverse patient population. Furthermore, the detailed assessment of efficacy and toxicity via standardized RTOG criteria enhances the comparability of our findings with those of other published prospective studies, despite the retrospective nature of the data.

CONCLUSIONS

This single-institution retrospective analysis revealed that short-term SBRT (36.25 to 40 Gy in 5 fractions), with a minimum follow-up of 24 months and a median follow-up of 45 months, for localized prostate cancer, including patients at HR, is associated with promising early efficacy and acceptable toxicity, even in the absence of routine fiducial or hydrogel spacer use. The favorable actuarial 5-year DFS and OS rates, coupled with a manageable toxicity profile, suggest that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer. However, a longer follow-up is necessary to confirm these findings and fully characterize the long-term efficacy and toxicity of this SBRT regimen. Nevertheless, the results contribute to the growing body of evidence suggesting that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer.

Prostate cancer is the most common cancer in US males, with an estimated 313,780 new cases and 35,770 deaths in 2025.¹ Several treatment options are available for localized prostate cancer that have similar outcomes, including active surveillance for low-risk cancers, surgery, or radiotherapy.^2,3 Conventional fractionation radiotherapy (CFRT) with 40 to 45 fractions over 8 to 9 weeks has been used for decades. Over the past 2 decades, moderate hypofractionation schedules with 2.4 to 3.4 Gy per fraction over 20 to 28 fractions have become standard, as many noninferiority randomized clinical trials (RCTs) such as CHHiP (UK),⁴ PROFIT (Canada and Europe),⁵ NRG Oncology RTOG 0415 (US),⁶ HYPRO (Netherlands),^7,8 and HYPO-RT-PC (Sweden and Denmark),⁹ have shown the noninferiority of moderately hypofractionated radiotherapy compared with CFRT. Notably, most of these noninferiority studies primarily included patients with low- or intermediate-risk prostate cancer, except for the HYPO-RT-PC trial,⁹ which also included patients with intermediate- and high-risk prostate cancer.

These noninferiority studies, along with technological advances in radiotherapy, such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and image-guided radiotherapy (IGRT), paved the path to ultrahypofractionated stereotactic body radiotherapy (SBRT) that is delivered in 5 fractions of ≥ 6 Gy. This high dose per fraction may have a radiobiologic advantage over conventional fractionation. The relatively low a/ß ratio of prostate cancer, estimated to be between 1 and 2, suggests that tumor cells may be particularly sensitive to the high doses per fraction delivered in SBRT.^10-13 Compared with CFRT, SBRT-induced tumor cell death may also be mediated through different pathways; this pathway appears to be generated in a dose-dependent manner, particularly with doses > 8 Gy per fraction.^14,15 Additionally, the higher a/ß ratio for the surrounding organs at risk, such as the bladder and rectum, theoretically allows for an improved therapeutic ratio window that maximizes tumor control while minimizing damage to healthy tissues.

A substantial body of evidence from prospective studies and meta-analyses supports the use of SBRT for localized prostate cancer. HYPO-RT-PC, a significant phase 3 noninferiority study, enrolled 1200 patients with intermediate (89%) and high-risk (11%) prostate cancer randomized between 2 arms, including CFRT to 78 Gy in 39 fractions and SBRT to 42.7 Gy in 7 fractions, treated 3 days weekly. After a median follow-up of 60 months, the estimated 5-year biochemical relapse-free survival rate was 84% in both groups.⁹ This trial was notable because it was the first randomized study to demonstrate that SBRT was noninferior to CFRT in intermediate- and high-risk prostate cancer patients. Another pivotal phase 3 trial, the PACE-B study, enrolled 874 patients to compare SBRT (36.25 Gy to the prostate gland, with a secondary dose of 40 Gy to the gross tumor volume where applicable, in 5 fractions) with CFRT (78 Gy in 39 fractions) and moderately hypofractionated radiotherapy (HFRT) (62 Gy in 20 fractions) in patients with low- or intermediate-risk prostate cancer. With a 74-month median follow-up, the study reported 5-year biochemical free rates of 94.6% for CFRT and 95.8% for SBRT, confirming the noninferiority of SBRT to CFRT.¹⁵

SBRT offers short, effective, and convenient treatment to many patients with localized prostate cancer. While previous guidelines were more restrictive, the March 2026 National Comprehensive Cancer Network (NCCN) guidelines now list SBRT as a preferred treatment modality for high-risk prostate cancer.¹⁶

Given the growing body of evidence supporting the efficacy and safety of SBRT, we implemented an SBRT program in 2014 at a tertiary care center for veterans. This retrospective study was undertaken to evaluate the early efficacy and toxicity of SBRT in patients with localized prostate cancer treated at our institution, including patients across all risk stratifications.

METHODS

We identified 242 patients diagnosed with prostate cancer who underwent SBRT treatment between November 2014 and October 2024 at Overland Park Veterans Affairs Radiation Oncology Clinic. For the final analysis, 46 patients with < 2 years of follow-up and 22 patients who died from causes other than prostate cancer were excluded, resulting in a cohort of 174 patients with ≥ 24-month follow-up.

Treatment

Patients eligible for staging underwent imaging according to NCCN guidelines, including computed tomography (CT) of the abdomen and pelvis, bone scintigraphy, or, in recent years, prostate-specific membrane antigen positron emission tomography, primarily used for unfavorable intermediate-risk (UIR) and high-risk (HR) cancers. Patients with a negative staging work-up for nodal or skeletal disease were included. Prior to planning the CT simulation, patients were given bowel preparation instructions, including a low-fiber and low-gas-producing diet, simethicone, and enemas, the night before and morning of the simulation. Patients were instructed to arrive with a comfortably full bladder, having not voided for 2 to 3 hours prior to the procedure. At Kansas City Veterans Affairs Medical Center (KCVAMC), SBRT treatment was generally restricted to patients with a baseline American Urological Association symptom score of 15 to 20 out of 35 and a prostate gland size < 80 mL to minimize the risk of acute urinary toxicity. We did not use intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast agents for planning CT simulation.

Patients were placed in a supine position, and a vacuum bag was used for immobilization. Following the CT simulation, the images were transferred to the Eclipse treatment planning system. The clinical target volume (CTV) encompassed the prostate and the proximal 1.0 cm of the seminal vesicles for Gleason score (GS) 1 to 2, and the entire seminal vesicle was included for GS 3 to 5, which is consistent with KCVAMC practice and established safety protocols. The planning target volume (PTV) was created by uniformly expanding the CTV by 5 to 7 mm, except for the posterior margin, which was limited to 3 to 5 mm. When elective nodal radiotherapy was planned for HR prostate cancer, the pelvic field for CT simulation started at the L-2 upper border, with the lower border extending to the lesser trochanter. The pelvic nodes were delineated per Radiation Therapy Oncology Group (RTOG) guidelines.¹⁷ The CTV nodes (CTVn), including common iliac, external and internal iliac nodes, obturator, and presacral nodes, were created by uniformly expanding the CTVn by 2 to 3 mm. Slice-by-slice corrections were made to avoid bowel overlap in these patients.

The use of androgen deprivation therapy (ADT) for a duration of 6 to 24 months was prescribed for patients with UIR or HR prostate cancer per NCCN guidelines.¹⁶ The prescribed dose to the PTV was 36.25 to 40 Gy (40 Gy was mostly used as a boost to the dominant lesion) in 5 fractions, with each fraction ranging from 7.25 to 8 Gy. For elective nodal radiotherapy in patients at HR, the prescribed dose was 25 Gy in 5 fractions. All patients were planned for VMAT, which aims to deliver ≥ 95% of the prescription dose to 95% of the PTV. Once the physician approved the treatment plan and physics quality assessment was completed, treatments commenced on an every-other-day schedule. Patients received the same bowel preparation instructions for each treatment as for the planning CT simulation. Daily treatment accuracy was confirmed via daily 3-dimensional cone-beam CT (CBCT) for IGRT. No fiducials or hydrogel rectal spacers were used.

Follow-up Schedule and Toxicity Assessment

Follow-up assessments were conducted 4 to 6 weeks after radiation therapy and then repeated every 6 months for 2 to 5 years, and annually thereafter. At each follow-up visit, patients were evaluated for genitourinary (GU) and gastrointestinal (GI) toxicity, according to RTOG toxicity criteria. Prostate-specific antigen (PSA) levels were monitored; in patients receiving ADT, testosterone levels were also checked.

Statistical Analysis

Biochemical failure was defined using the Phoenix definition (nadir PSA + 2 ng/mL). Differences between dose cohorts were assessed using the log-rank test for survival outcomes and X² testing for categorical variables. GU and GI toxicities were summarized as cumulative incidences of RTOG grade ≥ II events. Statistical significance was set at P < .05.

RESULTS

One hundred seventy-four patients were included in the retrospective review. Patients had a median follow-up of 45 months (range, 24-111) (Figure). The median age at treatment was 74 years (range, 51-88), and the median pretreatment PSA level was 11.9 ng/mL (range, 0.6-69.5). Twenty-six patients (14.9%) had a GS 1, 77 (44.3%) had GS 2, 41 (23.6%) had GS 3, 18 (10.3%) had GS 4, and 12 (6.9%) had GS 5. Fifty-one patients (29.3%) received elective pelvic nodal radiotherapy, and 93 patients (53.4%) received ADT (Table 1).

At 24 months follow-up, 6 patients (3.4%) had biochemical failures. One patient died from metastatic prostate cancer, and 5 patients are living with biochemical failure (Table 2). The actuarial 5-year overall survival (OS) rate was 99.4%, and the 5-year disease-free survival (DFS) rate was 96.6%. We performed a subanalysis comparing outcomes of the 36.25 Gy vs 40 Gy SBRT cohorts. There was no statistically significant difference in DFS, OS, or the cumulative incidence of grade II/III toxicity between patients treated with 40 Gy vs 36.25 Gy. Outcomes stratified by NCCN risk groups (low, intermediate, high/very high) are detailed in Table 3. As expected, DFS was slightly lower in the high-risk group, but overall disease control remained high across all stratifications.

The cumulative incidence of RTOG grade II and higher GU toxicity was 28.2% (Table 4). This included 46 patients (26.4%) with grade II GU toxicity and 2 patients (1.2%) who developed grade III GU complications (1 requiring self-catheterization and another a suprapubic catheter for urinary retention). One patient (0.6%) treated with a 40 Gy dose regimen experienced a grade IV GU complication in the form of a rectovesical fistula necessitating surgical intervention.

The cumulative incidence of RTOG grade II or higher GI toxicity was 3.4%, and no grade III or IV gastrointestinal toxicities were observed during the follow-up period. Importantly, intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast were not routinely used in this cohort of patients.

The high rates of actuarial 5-year DFS and OS observed suggest a favorable initial response to the SBRT regimen employed at KCVAMC. However, given the potential for late recurrence in patients with prostate cancer, longer follow-up is essential to determine the durability of these outcomes. The observed GU toxicity rate of 28.2% for grade II and higher events warrants careful consideration and compares with other published data on SBRT for prostate cancer.¹⁵ The occurrence of a grade IV rectovesical fistula, although rare, is a notable adverse event that warrants discussion in the context of the treatment approach. The low incidence of grade II or higher GI toxicity is an encouraging finding, particularly given that hydrogel rectal spacers are not routinely used to minimize rectal exposure.

DISCUSSION

The primary objective of this retrospective study was to evaluate the outcomes of SBRT for patients with localized prostate cancer treated at KCVAMC and to compare these results with those reported in the literature. Our findings demonstrate promising intermediate-term efficacy, with an estimated 5-year DFS of 96.6% and OS of 99.4% at a median follow-up of 45 months. Furthermore, the observed toxicity profile appears acceptable, with a cumulative grade II and higher GU toxicity rate of 28.2% and a grade II or higher GI toxicity rate of 3.4%. Notably, these outcomes were achieved without the routine use of intraprostatic fiducials or hydrogel rectal spacers.

Two pivotal randomized phase 3 trials have established the noninferiority of ultrahypofractionated radiotherapy (UHRT) with SBRT over conventional fractionation. The HYPO-RT-PC trial compared SBRT (42.7 Gy in 7 fractions) with conventional fractionation (78 Gy in 39 fractions) in intermediate- and high-risk patients with prostate cancer and reported a 5-year biochemical relapse-free survival of 84% in both arms.⁹ The PACE-B trial, which included patients at low- and intermediate-risk, compared SBRT (36.25 Gy in 5 fractions) with conventional or moderate HFRT and reported a 5-year biochemical control rate of 95.8% in the SBRT arm and 94.6% in the control arm.¹⁵

A comprehensive review and meta-analysis of 7 phase 3 studies involving 6795 patients compared different radiotherapy regimens, namely, UHRT, HFRT, and CFRT, and reported that after 5 years, the DFS rates were 85.1% for CFRT, 86% for HFRT, and 85% for UHRT, with no significant difference in toxicity among the 3 different treatment approaches.¹⁸ This suggests that shorter, more intense radiotherapy schedules (UHRT and HFRT) may be as effective and safe as traditional, longer courses of radiation.

There are multiple published nonrandomized prospective trials in which thousands of patients with extreme hypofractionation have been treated with different doses, fractions, and techniques. While heterogeneity and limited long-term follow-up in the existing evidence are acknowledged, these data suggest that prostate SBRT provides appropriate biochemical control with few high-grade toxicities, supporting its ongoing global use and justifying further prospective investigations. Comparative data are shown in Table 5. Several ongoing studies are evaluating noninferiority, superiority, and cost-effectiveness using different methodologies (Table 6).^9,15,19-24

This study’s efficacy outcomes, particularly the high DFS rate, are consistent with the findings from these landmark trials, suggesting that the SBRT regimen used at KCVAMC is effective in achieving early disease control despite 17.2% of patients having high-risk disease. The GU toxicity observed in this study, with a 28.2% rate of grade II or higher events, is also comparable with the 26.9% reported in the 5-fraction SBRT arm of the PACE-B trial, which had a longer median follow-up of 74 months.¹⁵ It is important to note that a portion of these grade II events occurred in patients who were already on a blockers for pre-existing lower urinary tract symptoms before starting radiotherapy, which may inflate the observed cumulative acute toxicity score.

A critical comparison is how SBRT toxicity aligns with moderate hypofractionation (eg, 60 Gy in 20 fractions or 70 Gy in 28 fractions as reported by others).^4,6 Our observed grade III and higher GU toxicity rate (1.7%) and grade III and higher GI toxicity rate (0%) are highly favorable when compared with historical moderate hypofractionation data, which typically report grade III GU toxicity in the range of 2% to 3% and grade III GI toxicity around 1% to 2%. This suggests that despite the higher dose per fraction, SBRT does not necessarily lead to increased severe acute toxicity, potentially offering a superior therapeutic ratio for GI and GU sparing.

However, the occurrence of a grade IV rectovesical fistula in 1 patient (0.6%)—who received the 40 Gy dose—was a serious complication that warrants careful consideration. This rare, but severe, complication in the higher dose cohort underscores the potential for increased organ-at-risk toxicity, particularly in the absence of a hydrogel rectal spacer, which is designed to mitigate high-dose rectal exposure. While the overall rate of significant GU toxicity remains low, this event highlights the potential risks associated with SBRT. Hydrogel rectal spacers are designed to increase the distance between the prostate and the rectum, which can reduce the rectal radiation dose and potentially mitigate the risk of such fistulas. The low rate of grade II or worse GI toxicity (3.4%) in our study is noteworthy, especially considering that hydrogel spacers were not routinely used. This finding aligns with the 2.5% GI toxicity rate reported in the SBRT arm of the PACE-B trial, suggesting that careful treatment planning and delivery techniques, such as VMAT-IMRT and daily CBCT for IGRT, may contribute to minimizing GI toxicity even without the use of rectal spacers.¹⁵ The exclusive use of 3-dimensional CBCT for IGRT in our study, without the use of fiducial markers, suggests that accurate target localization can be achieved with this approach, contributing to the observed efficacy and reduced toxicity.

Strengths and Limitations

This study’s retrospective, single-center design may have introduced selection bias. The median follow-up of 45 months, while substantial, is still relatively short for assessing very late toxicities and long-term oncologic outcomes in prostate cancer, which is known for late recurrences. Additionally, the lack of a direct comparison group within KCVAMC limits the ability to definitively attribute the observed outcomes solely to SBRT treatment. However, the strengths of this study include the inclusion of a consecutive series of veteran patients with localized prostate cancer across all risk categories, providing a real-world perspective on SBRT outcomes in a diverse patient population. Furthermore, the detailed assessment of efficacy and toxicity via standardized RTOG criteria enhances the comparability of our findings with those of other published prospective studies, despite the retrospective nature of the data.

CONCLUSIONS

This single-institution retrospective analysis revealed that short-term SBRT (36.25 to 40 Gy in 5 fractions), with a minimum follow-up of 24 months and a median follow-up of 45 months, for localized prostate cancer, including patients at HR, is associated with promising early efficacy and acceptable toxicity, even in the absence of routine fiducial or hydrogel spacer use. The favorable actuarial 5-year DFS and OS rates, coupled with a manageable toxicity profile, suggest that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer. However, a longer follow-up is necessary to confirm these findings and fully characterize the long-term efficacy and toxicity of this SBRT regimen. Nevertheless, the results contribute to the growing body of evidence suggesting that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disease that arises from loss-of-function mutations in the FLCN gene. FLCN encodes folliculin, which is presumed to function as a tumor suppressor, though its precise role is incompletely understood.^1,2 BHD is characterized by multiple pulmonary cysts leading to recurrent spontaneous pneumothoraces, cutaneous lesions—specifically fibrofolliculomas—and an increased risk of renal malignancies. Diagnosing BHD is challenging due to the variable presentation of the disease. Some patients may only have cystic lung diseases, while others may not have characteristic skin lesions.^3-5 It is important to maintain awareness of BHD, especially when the diagnosis dictates the need for genetic counseling.

Case Presentation

A male veteran in his 60s, who was a lifelong nonsmoker with a history of extensive bullous emphysema and recurrent pneumothoraces, presented to the Veterans Affairs Greater Los Angeles Healthcare System pulmonary clinic while transferring care from a separate institution.

According to the patient, the first pneumothorax episode occurred about 20 years before presentation, followed by a recurrence a few years later after he was diagnosed with emphysema. He underwent pleurodesis of the right lung during his service abroad. Another episode nearly a decade after the first pneumothorax necessitated pleurodesis of the left lung (Figure 1). The patient's family history revealed pulmonary cysts in 1 immediate family member but no history of renal tumors. Notably, his mother passed away at a young age due to tuberculosis.

On physical examination, numerous skin tags and acrochordons on the face were observed, which had been stable for > 30 years. Despite a slow decline in exercise capacity following pleurodesis, the patient could still walk multiple miles daily and climb 3 flights of stairs before needing to rest. Pulmonary function testing (PFT) showed a forced expiratory volume in 1 second (FEV₁)/forced vital capacity ratio of 0.84 with reduced FEV₁, total lung capacity (TLC), and diffusion capacity for carbon monoxide (DL_CO), indicating a mild restrictive ventilatory defect and reduced diffusing capacity.

Laboratory results revealed a normal α-1 antitrypsin level: 133 mg/dL (reference, 83-199 mg/dL), with a Pi*MS phenotype and undetectable antinuclear antibodies. The most recent chest computed tomography (CT) in 2019, displayed paraseptal and centrilobular emphysema, scattered blebs, and scarring consistent with prior pleurodesis procedures (Figure 2).

Genetic testing for the FLCN gene revealed heterozygous pathogenic mutation: c.1285del and p.His429Thrfs*39, which confirmed the diagnosis of BHD. A shave biopsy of a postauricular papular lesion confirmed a histologic pattern of fibrofolliculoma/trichodiscoma.

Follow-up and Outcomes

After confirmation of the BHD diagnosis, the patient was referred to genetic counseling and scheduled for annual magnetic resonance imaging (MRI) of the abdomen and pelvis to screen for renal malignancies. As the patient was able to establish care with a new long-term primary care practitioner in the outpatient setting, he continues regular follow-up visits in the pulmonary clinic with stable respiratory symptoms and no recurrent pneumothoraces thus far.

Discussion

Differential Diagnoses of Cystic Pulmonary Lesions

BHD is an important differential diagnosis to consider in the presentation of diffuse cystic lung diseases. Still, 2 other crucial considerations are pulmonary Langerhans cell histiocytosis (PLCH) and lymphangioleiomyomatosis (LAM), which occur at slightly higher frequencies than BHD.⁶

One of the first steps in radiographically evaluating cystic lung diseases is to characterize the cysts. The Fleischner Society defines true cysts as a “round parenchymal lucency or low-attenuating area with a well-defined interface with normal lung.”⁷ Mimics of cystic lesions may include cavitary lung lesions, thick-walled spaces within another area of mass, nodule, or consolidation. Another mimic is a pneumatocele, a pseudocyst that lacks epithelial lining and may be secondary to bacterial pneumonia, pneumocystis infections, trauma, or prior mechanical ventilation.⁸After characterizing true cysts, different patterns of cystic lesions can also be associated with specific diseases. Cysts in PLCH are commonly more uniform and round, whereas the cysts in LAM may be more irregularly shaped. ⁹ Cysts in BHD may be larger and predominantly located in basal and paramediastinal areas.⁴LAM is associated with tuberous sclerosis, which can also present with skin lesions (angiofibromas) and renal tumors (angiomyolipomas), thus creating a very similar picture to BHD. Therefore, tissue biopsies of skin lesions are essential as histopathology can identify characteristic fibrofolliculomas specific to BHD. While genetic testing would also strongly support the diagnosis of BHD, it is essential to note that negative genetic testing does not rule out BHD.⁴Lastly, lymphoid interstitial pneumonia (LIP) is another important consideration in the differential diagnosis of cystic lung diseases. LIP presents with not only perivascular cysts and centrilobular nodules but also diffuse ground-glass attenuation.¹⁰ In contrast to BHD, LIP is associated with autoimmune diseases such as Sjögren syndrome and infectious diseases such as HIV; thus, it may be differentiated from BHD by the presence of underlying disease processes and may warrant serologic testing for potential rheumatologic disorders.

Characteristics and Diagnostic Criteria


Cystic lung disease is the most common presentation of BHD. It presents in > 80% of cases and confers a 50-fold increase in the risk of spontaneous pneumothorax compared with the general population.^4,11 Recurrent pneumothoraces are observed in about 25% to 30% of patients with BHD, typically occurring between the third and fifth decades of life and at significantly decreased rates after 50 years of age.¹² A spontaneous pneumothorax might serve as the initial and perhaps the sole clinical presentation for some patients with BHD, but others may present with other respiratory symptoms such as cough and exertional dyspnea. PFT results may be normal or reveal a mild restrictive ventilatory defect and reduced DL_CO, as reported in a few cases.⁶ The management of pulmonary complications primarily revolves around reducing the risk of pneumothoraces, which includes precautions such as avoiding positive pressure ventilation and air travel. Early pleurodesis with the first occurrence of a spontaneous pneumothorax is considered in some cases.¹³

The distinctive dermatologic features associated with BHD include multiple white papules primarily found on the nose and face. Pathologically, these manifestations have a range of histologic distinctions, from fibrofolliculomas to benign hamartomas of the hair follicles and trichodiscomas.⁵ The diagnostic criteria outlined by Menko et al note that confirmation of BHD requires the presence of either ≥ 5 pathologically confirmed fibrofolliculomas or trichodiscomas, a documented pathogenic FLCN gene mutation, or the fulfillment of 2 minor criteria. These minor criteria include the presence of multiple lung cysts, early-onset renal cancer, or a first-degree relative with BHD.⁵

Recurrent Pneumothoraces Management

After the first episode of spontaneous pneumothorax, early pleurodesis is indicated as the risk of recurrence can be as high as 75%.^4,14 Specific pleurodesis modalities have shown promising results, such as total pleural covering with cellulose mesh. In a small retrospective review, cellulose mesh demonstrated a significant reduction in the recurrence rate of pneumothorax at 7.5 years for patients with BHD compared with partial covering.¹⁵ Apart from preventing further pneumothorax episodes in the affected lung, it is also important to highlight patient education and monitoring after initial pleurodesis, as the contralateral lung is also at risk. As demonstrated in this case, the patient had received pleurodesis of his right lung but experienced another pneumothorax of his contralateral lung a few years later.

Lastly, the patient was advised to avoid air travel altogether; however, current data may suggest that air travel may not be an absolute contraindication for patients with BHD. Although the literature on this topic is limited, a retrospective study by Johannesma et al involving 158 patients with BHD surveyed on pneumothorax occurrence after air travel indicated a calculated risk of 0.63% per flight. Notably, only 3 of 13 patients with BHD and recurrent pneumothoraces after travel had undergone pleurodesis in the past.¹⁶ Therefore, counseling patients on the potential risks of air travel and allowing essential flights while diligently monitoring for symptoms during and after travel may be a reasonable, patient-centered approach in contrast to a complete restriction on air travel.

Timing to Diagnosis

Diagnosing BHD is challenging and often delayed. In a 2022 study by Steinlein et al, the average delay in BHD diagnoses in their cohort was 9.3 years, with 4 patients also diagnosed with renal malignancy during the study period.¹⁷ The difficulty in diagnosis can be attributed to the heterogeneous presentation among affected family members, some of whom may exclusively exhibit pulmonary cystic lesions without dermatologic findings.

A lack of longitudinal care for this patient may have contributed to the diagnostic delay. The patient had pneumothorax events across separate care settings and locations, and due to employment-related relocations, he often re-established care at various health care systems. This case highlights the importance of continuity of care, especially in BHD, where monitoring for renal tumors is also essential to long-term management.^17,18

Renal Tumor Monitoring

Finally, once BHD is diagnosed, one of the most important considerations is to begin routine monitoring for renal malignancies. Current recommendations advise starting lifelong renal cancer screening, even as early as age 20 years, with annual MRIs, as renal ultrasound may not be sufficiently sensitive to detect smaller lesions.¹⁹ The screening interval can be extended to every 2 years for patients without a family history of renal tumors or suspicious renal lesions. If tumors are found, then nephron-sparing surgery is recommended, given the potential for the development of chronic renal insufficiency in patients with BHD.²⁰

Conclusions

BHD is a rare and complex syndrome in which early recognition and diagnosis play a pivotal role in preventing potentially severe complications such as renal malignancies. Suspicion of a genetic disorder, such as BHD, LAM, or PLCH, should arise in patients who experience spontaneous pneumothorax, especially in the presence of multiple cystic lesions or a family history of pneumothoraces. Early consideration of pleurodesis after the first spontaneous pneumothorax is advisable. The complex presentation of BHD contributes to the difficulty of diagnosis and may delay recognition, which can be exacerbated by variable continuity of care.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disease that arises from loss-of-function mutations in the FLCN gene. FLCN encodes folliculin, which is presumed to function as a tumor suppressor, though its precise role is incompletely understood.^1,2 BHD is characterized by multiple pulmonary cysts leading to recurrent spontaneous pneumothoraces, cutaneous lesions—specifically fibrofolliculomas—and an increased risk of renal malignancies. Diagnosing BHD is challenging due to the variable presentation of the disease. Some patients may only have cystic lung diseases, while others may not have characteristic skin lesions.^3-5 It is important to maintain awareness of BHD, especially when the diagnosis dictates the need for genetic counseling.

Case Presentation

A male veteran in his 60s, who was a lifelong nonsmoker with a history of extensive bullous emphysema and recurrent pneumothoraces, presented to the Veterans Affairs Greater Los Angeles Healthcare System pulmonary clinic while transferring care from a separate institution.

According to the patient, the first pneumothorax episode occurred about 20 years before presentation, followed by a recurrence a few years later after he was diagnosed with emphysema. He underwent pleurodesis of the right lung during his service abroad. Another episode nearly a decade after the first pneumothorax necessitated pleurodesis of the left lung (Figure 1). The patient's family history revealed pulmonary cysts in 1 immediate family member but no history of renal tumors. Notably, his mother passed away at a young age due to tuberculosis.

On physical examination, numerous skin tags and acrochordons on the face were observed, which had been stable for > 30 years. Despite a slow decline in exercise capacity following pleurodesis, the patient could still walk multiple miles daily and climb 3 flights of stairs before needing to rest. Pulmonary function testing (PFT) showed a forced expiratory volume in 1 second (FEV₁)/forced vital capacity ratio of 0.84 with reduced FEV₁, total lung capacity (TLC), and diffusion capacity for carbon monoxide (DL_CO), indicating a mild restrictive ventilatory defect and reduced diffusing capacity.

Laboratory results revealed a normal α-1 antitrypsin level: 133 mg/dL (reference, 83-199 mg/dL), with a Pi*MS phenotype and undetectable antinuclear antibodies. The most recent chest computed tomography (CT) in 2019, displayed paraseptal and centrilobular emphysema, scattered blebs, and scarring consistent with prior pleurodesis procedures (Figure 2).

Genetic testing for the FLCN gene revealed heterozygous pathogenic mutation: c.1285del and p.His429Thrfs*39, which confirmed the diagnosis of BHD. A shave biopsy of a postauricular papular lesion confirmed a histologic pattern of fibrofolliculoma/trichodiscoma.

Follow-up and Outcomes

After confirmation of the BHD diagnosis, the patient was referred to genetic counseling and scheduled for annual magnetic resonance imaging (MRI) of the abdomen and pelvis to screen for renal malignancies. As the patient was able to establish care with a new long-term primary care practitioner in the outpatient setting, he continues regular follow-up visits in the pulmonary clinic with stable respiratory symptoms and no recurrent pneumothoraces thus far.

Discussion

Differential Diagnoses of Cystic Pulmonary Lesions

BHD is an important differential diagnosis to consider in the presentation of diffuse cystic lung diseases. Still, 2 other crucial considerations are pulmonary Langerhans cell histiocytosis (PLCH) and lymphangioleiomyomatosis (LAM), which occur at slightly higher frequencies than BHD.⁶

One of the first steps in radiographically evaluating cystic lung diseases is to characterize the cysts. The Fleischner Society defines true cysts as a “round parenchymal lucency or low-attenuating area with a well-defined interface with normal lung.”⁷ Mimics of cystic lesions may include cavitary lung lesions, thick-walled spaces within another area of mass, nodule, or consolidation. Another mimic is a pneumatocele, a pseudocyst that lacks epithelial lining and may be secondary to bacterial pneumonia, pneumocystis infections, trauma, or prior mechanical ventilation.⁸After characterizing true cysts, different patterns of cystic lesions can also be associated with specific diseases. Cysts in PLCH are commonly more uniform and round, whereas the cysts in LAM may be more irregularly shaped. ⁹ Cysts in BHD may be larger and predominantly located in basal and paramediastinal areas.⁴LAM is associated with tuberous sclerosis, which can also present with skin lesions (angiofibromas) and renal tumors (angiomyolipomas), thus creating a very similar picture to BHD. Therefore, tissue biopsies of skin lesions are essential as histopathology can identify characteristic fibrofolliculomas specific to BHD. While genetic testing would also strongly support the diagnosis of BHD, it is essential to note that negative genetic testing does not rule out BHD.⁴Lastly, lymphoid interstitial pneumonia (LIP) is another important consideration in the differential diagnosis of cystic lung diseases. LIP presents with not only perivascular cysts and centrilobular nodules but also diffuse ground-glass attenuation.¹⁰ In contrast to BHD, LIP is associated with autoimmune diseases such as Sjögren syndrome and infectious diseases such as HIV; thus, it may be differentiated from BHD by the presence of underlying disease processes and may warrant serologic testing for potential rheumatologic disorders.

Characteristics and Diagnostic Criteria


Cystic lung disease is the most common presentation of BHD. It presents in > 80% of cases and confers a 50-fold increase in the risk of spontaneous pneumothorax compared with the general population.^4,11 Recurrent pneumothoraces are observed in about 25% to 30% of patients with BHD, typically occurring between the third and fifth decades of life and at significantly decreased rates after 50 years of age.¹² A spontaneous pneumothorax might serve as the initial and perhaps the sole clinical presentation for some patients with BHD, but others may present with other respiratory symptoms such as cough and exertional dyspnea. PFT results may be normal or reveal a mild restrictive ventilatory defect and reduced DL_CO, as reported in a few cases.⁶ The management of pulmonary complications primarily revolves around reducing the risk of pneumothoraces, which includes precautions such as avoiding positive pressure ventilation and air travel. Early pleurodesis with the first occurrence of a spontaneous pneumothorax is considered in some cases.¹³

The distinctive dermatologic features associated with BHD include multiple white papules primarily found on the nose and face. Pathologically, these manifestations have a range of histologic distinctions, from fibrofolliculomas to benign hamartomas of the hair follicles and trichodiscomas.⁵ The diagnostic criteria outlined by Menko et al note that confirmation of BHD requires the presence of either ≥ 5 pathologically confirmed fibrofolliculomas or trichodiscomas, a documented pathogenic FLCN gene mutation, or the fulfillment of 2 minor criteria. These minor criteria include the presence of multiple lung cysts, early-onset renal cancer, or a first-degree relative with BHD.⁵

Recurrent Pneumothoraces Management

After the first episode of spontaneous pneumothorax, early pleurodesis is indicated as the risk of recurrence can be as high as 75%.^4,14 Specific pleurodesis modalities have shown promising results, such as total pleural covering with cellulose mesh. In a small retrospective review, cellulose mesh demonstrated a significant reduction in the recurrence rate of pneumothorax at 7.5 years for patients with BHD compared with partial covering.¹⁵ Apart from preventing further pneumothorax episodes in the affected lung, it is also important to highlight patient education and monitoring after initial pleurodesis, as the contralateral lung is also at risk. As demonstrated in this case, the patient had received pleurodesis of his right lung but experienced another pneumothorax of his contralateral lung a few years later.

Lastly, the patient was advised to avoid air travel altogether; however, current data may suggest that air travel may not be an absolute contraindication for patients with BHD. Although the literature on this topic is limited, a retrospective study by Johannesma et al involving 158 patients with BHD surveyed on pneumothorax occurrence after air travel indicated a calculated risk of 0.63% per flight. Notably, only 3 of 13 patients with BHD and recurrent pneumothoraces after travel had undergone pleurodesis in the past.¹⁶ Therefore, counseling patients on the potential risks of air travel and allowing essential flights while diligently monitoring for symptoms during and after travel may be a reasonable, patient-centered approach in contrast to a complete restriction on air travel.

Timing to Diagnosis

Diagnosing BHD is challenging and often delayed. In a 2022 study by Steinlein et al, the average delay in BHD diagnoses in their cohort was 9.3 years, with 4 patients also diagnosed with renal malignancy during the study period.¹⁷ The difficulty in diagnosis can be attributed to the heterogeneous presentation among affected family members, some of whom may exclusively exhibit pulmonary cystic lesions without dermatologic findings.

A lack of longitudinal care for this patient may have contributed to the diagnostic delay. The patient had pneumothorax events across separate care settings and locations, and due to employment-related relocations, he often re-established care at various health care systems. This case highlights the importance of continuity of care, especially in BHD, where monitoring for renal tumors is also essential to long-term management.^17,18

Renal Tumor Monitoring

Finally, once BHD is diagnosed, one of the most important considerations is to begin routine monitoring for renal malignancies. Current recommendations advise starting lifelong renal cancer screening, even as early as age 20 years, with annual MRIs, as renal ultrasound may not be sufficiently sensitive to detect smaller lesions.¹⁹ The screening interval can be extended to every 2 years for patients without a family history of renal tumors or suspicious renal lesions. If tumors are found, then nephron-sparing surgery is recommended, given the potential for the development of chronic renal insufficiency in patients with BHD.²⁰

Conclusions

BHD is a rare and complex syndrome in which early recognition and diagnosis play a pivotal role in preventing potentially severe complications such as renal malignancies. Suspicion of a genetic disorder, such as BHD, LAM, or PLCH, should arise in patients who experience spontaneous pneumothorax, especially in the presence of multiple cystic lesions or a family history of pneumothoraces. Early consideration of pleurodesis after the first spontaneous pneumothorax is advisable. The complex presentation of BHD contributes to the difficulty of diagnosis and may delay recognition, which can be exacerbated by variable continuity of care.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disease that arises from loss-of-function mutations in the FLCN gene. FLCN encodes folliculin, which is presumed to function as a tumor suppressor, though its precise role is incompletely understood.^1,2 BHD is characterized by multiple pulmonary cysts leading to recurrent spontaneous pneumothoraces, cutaneous lesions—specifically fibrofolliculomas—and an increased risk of renal malignancies. Diagnosing BHD is challenging due to the variable presentation of the disease. Some patients may only have cystic lung diseases, while others may not have characteristic skin lesions.^3-5 It is important to maintain awareness of BHD, especially when the diagnosis dictates the need for genetic counseling.

Case Presentation

A male veteran in his 60s, who was a lifelong nonsmoker with a history of extensive bullous emphysema and recurrent pneumothoraces, presented to the Veterans Affairs Greater Los Angeles Healthcare System pulmonary clinic while transferring care from a separate institution.

According to the patient, the first pneumothorax episode occurred about 20 years before presentation, followed by a recurrence a few years later after he was diagnosed with emphysema. He underwent pleurodesis of the right lung during his service abroad. Another episode nearly a decade after the first pneumothorax necessitated pleurodesis of the left lung (Figure 1). The patient's family history revealed pulmonary cysts in 1 immediate family member but no history of renal tumors. Notably, his mother passed away at a young age due to tuberculosis.

On physical examination, numerous skin tags and acrochordons on the face were observed, which had been stable for > 30 years. Despite a slow decline in exercise capacity following pleurodesis, the patient could still walk multiple miles daily and climb 3 flights of stairs before needing to rest. Pulmonary function testing (PFT) showed a forced expiratory volume in 1 second (FEV₁)/forced vital capacity ratio of 0.84 with reduced FEV₁, total lung capacity (TLC), and diffusion capacity for carbon monoxide (DL_CO), indicating a mild restrictive ventilatory defect and reduced diffusing capacity.

Laboratory results revealed a normal α-1 antitrypsin level: 133 mg/dL (reference, 83-199 mg/dL), with a Pi*MS phenotype and undetectable antinuclear antibodies. The most recent chest computed tomography (CT) in 2019, displayed paraseptal and centrilobular emphysema, scattered blebs, and scarring consistent with prior pleurodesis procedures (Figure 2).

Genetic testing for the FLCN gene revealed heterozygous pathogenic mutation: c.1285del and p.His429Thrfs*39, which confirmed the diagnosis of BHD. A shave biopsy of a postauricular papular lesion confirmed a histologic pattern of fibrofolliculoma/trichodiscoma.

Follow-up and Outcomes

After confirmation of the BHD diagnosis, the patient was referred to genetic counseling and scheduled for annual magnetic resonance imaging (MRI) of the abdomen and pelvis to screen for renal malignancies. As the patient was able to establish care with a new long-term primary care practitioner in the outpatient setting, he continues regular follow-up visits in the pulmonary clinic with stable respiratory symptoms and no recurrent pneumothoraces thus far.

Discussion

Differential Diagnoses of Cystic Pulmonary Lesions

BHD is an important differential diagnosis to consider in the presentation of diffuse cystic lung diseases. Still, 2 other crucial considerations are pulmonary Langerhans cell histiocytosis (PLCH) and lymphangioleiomyomatosis (LAM), which occur at slightly higher frequencies than BHD.⁶

One of the first steps in radiographically evaluating cystic lung diseases is to characterize the cysts. The Fleischner Society defines true cysts as a “round parenchymal lucency or low-attenuating area with a well-defined interface with normal lung.”⁷ Mimics of cystic lesions may include cavitary lung lesions, thick-walled spaces within another area of mass, nodule, or consolidation. Another mimic is a pneumatocele, a pseudocyst that lacks epithelial lining and may be secondary to bacterial pneumonia, pneumocystis infections, trauma, or prior mechanical ventilation.⁸After characterizing true cysts, different patterns of cystic lesions can also be associated with specific diseases. Cysts in PLCH are commonly more uniform and round, whereas the cysts in LAM may be more irregularly shaped. ⁹ Cysts in BHD may be larger and predominantly located in basal and paramediastinal areas.⁴LAM is associated with tuberous sclerosis, which can also present with skin lesions (angiofibromas) and renal tumors (angiomyolipomas), thus creating a very similar picture to BHD. Therefore, tissue biopsies of skin lesions are essential as histopathology can identify characteristic fibrofolliculomas specific to BHD. While genetic testing would also strongly support the diagnosis of BHD, it is essential to note that negative genetic testing does not rule out BHD.⁴Lastly, lymphoid interstitial pneumonia (LIP) is another important consideration in the differential diagnosis of cystic lung diseases. LIP presents with not only perivascular cysts and centrilobular nodules but also diffuse ground-glass attenuation.¹⁰ In contrast to BHD, LIP is associated with autoimmune diseases such as Sjögren syndrome and infectious diseases such as HIV; thus, it may be differentiated from BHD by the presence of underlying disease processes and may warrant serologic testing for potential rheumatologic disorders.

Characteristics and Diagnostic Criteria


Cystic lung disease is the most common presentation of BHD. It presents in > 80% of cases and confers a 50-fold increase in the risk of spontaneous pneumothorax compared with the general population.^4,11 Recurrent pneumothoraces are observed in about 25% to 30% of patients with BHD, typically occurring between the third and fifth decades of life and at significantly decreased rates after 50 years of age.¹² A spontaneous pneumothorax might serve as the initial and perhaps the sole clinical presentation for some patients with BHD, but others may present with other respiratory symptoms such as cough and exertional dyspnea. PFT results may be normal or reveal a mild restrictive ventilatory defect and reduced DL_CO, as reported in a few cases.⁶ The management of pulmonary complications primarily revolves around reducing the risk of pneumothoraces, which includes precautions such as avoiding positive pressure ventilation and air travel. Early pleurodesis with the first occurrence of a spontaneous pneumothorax is considered in some cases.¹³

The distinctive dermatologic features associated with BHD include multiple white papules primarily found on the nose and face. Pathologically, these manifestations have a range of histologic distinctions, from fibrofolliculomas to benign hamartomas of the hair follicles and trichodiscomas.⁵ The diagnostic criteria outlined by Menko et al note that confirmation of BHD requires the presence of either ≥ 5 pathologically confirmed fibrofolliculomas or trichodiscomas, a documented pathogenic FLCN gene mutation, or the fulfillment of 2 minor criteria. These minor criteria include the presence of multiple lung cysts, early-onset renal cancer, or a first-degree relative with BHD.⁵

Recurrent Pneumothoraces Management

After the first episode of spontaneous pneumothorax, early pleurodesis is indicated as the risk of recurrence can be as high as 75%.^4,14 Specific pleurodesis modalities have shown promising results, such as total pleural covering with cellulose mesh. In a small retrospective review, cellulose mesh demonstrated a significant reduction in the recurrence rate of pneumothorax at 7.5 years for patients with BHD compared with partial covering.¹⁵ Apart from preventing further pneumothorax episodes in the affected lung, it is also important to highlight patient education and monitoring after initial pleurodesis, as the contralateral lung is also at risk. As demonstrated in this case, the patient had received pleurodesis of his right lung but experienced another pneumothorax of his contralateral lung a few years later.

Lastly, the patient was advised to avoid air travel altogether; however, current data may suggest that air travel may not be an absolute contraindication for patients with BHD. Although the literature on this topic is limited, a retrospective study by Johannesma et al involving 158 patients with BHD surveyed on pneumothorax occurrence after air travel indicated a calculated risk of 0.63% per flight. Notably, only 3 of 13 patients with BHD and recurrent pneumothoraces after travel had undergone pleurodesis in the past.¹⁶ Therefore, counseling patients on the potential risks of air travel and allowing essential flights while diligently monitoring for symptoms during and after travel may be a reasonable, patient-centered approach in contrast to a complete restriction on air travel.

Timing to Diagnosis

Diagnosing BHD is challenging and often delayed. In a 2022 study by Steinlein et al, the average delay in BHD diagnoses in their cohort was 9.3 years, with 4 patients also diagnosed with renal malignancy during the study period.¹⁷ The difficulty in diagnosis can be attributed to the heterogeneous presentation among affected family members, some of whom may exclusively exhibit pulmonary cystic lesions without dermatologic findings.

A lack of longitudinal care for this patient may have contributed to the diagnostic delay. The patient had pneumothorax events across separate care settings and locations, and due to employment-related relocations, he often re-established care at various health care systems. This case highlights the importance of continuity of care, especially in BHD, where monitoring for renal tumors is also essential to long-term management.^17,18

Renal Tumor Monitoring

Finally, once BHD is diagnosed, one of the most important considerations is to begin routine monitoring for renal malignancies. Current recommendations advise starting lifelong renal cancer screening, even as early as age 20 years, with annual MRIs, as renal ultrasound may not be sufficiently sensitive to detect smaller lesions.¹⁹ The screening interval can be extended to every 2 years for patients without a family history of renal tumors or suspicious renal lesions. If tumors are found, then nephron-sparing surgery is recommended, given the potential for the development of chronic renal insufficiency in patients with BHD.²⁰

Conclusions

BHD is a rare and complex syndrome in which early recognition and diagnosis play a pivotal role in preventing potentially severe complications such as renal malignancies. Suspicion of a genetic disorder, such as BHD, LAM, or PLCH, should arise in patients who experience spontaneous pneumothorax, especially in the presence of multiple cystic lesions or a family history of pneumothoraces. Early consideration of pleurodesis after the first spontaneous pneumothorax is advisable. The complex presentation of BHD contributes to the difficulty of diagnosis and may delay recognition, which can be exacerbated by variable continuity of care.

Patients make unplanned appointments after elective soft tissue hand surgery for real or perceived complications when they experience pain, anxiety, or fear. Unplanned appointments can create travel and financial burdens for patients and families. These appointments take time away from scheduled appointments and can contribute to late arrivals and delays in other clinics. Unscheduled appointments contribute to poor access when staff are diverted from scheduled appointments. If predictive factors can be identified, unplanned appointments may either be ameliorated or avoided with better perioperative risk management or education.

Methods

The US Department of Veterans Affairs (VA) North Florida/South Georgia Veterans Health System (NFSGVAHS) and University of Florida Institutional Review Board approved a retrospective chart review of all plastic surgery cases performed at the Malcom Randall VA Medical Center (MRVAMC) and Lake City VAMC operating rooms from July 1, 2018, through December 31, 2019, and January 1, 2021, through June 30, 2022 (nonurgent surgeries were discouraged during the COVID-19 pandemic). Elective soft tissue hand surgery cases were identified based on the operative description found in the Surgical Service Surgeon Staffing Report reviewed monthly by the Service Chief. Potential indicators of unplanned visits were recorded, including age; sex; diagnosis of diabetes, depression, anxiety, or posttraumatic stress disorder (PTSD); current smoking status; and residential zip code. We used the first 3 digits of the patients’ zip codes, which indicate region, as an estimate of proximity to the MRVAMC, which has a 50-county catchment area across North Florida and South Georgia. Diagnoses were found on the “problem list” from the electronic health record documented in the history and physical examinations before surgery. Clinic notes were examined for 3 months postsurgery to identify unplanned postoperative visits and the reason for the appointment. A χ² analysis was conducted using Excel Version 2402. P < .05 was used to determine whether age (> 60 years), sex, proximity to MRVAMC, diabetes, smoking, depression, anxiety, or PTSD were statistically significant independent risk factors for these appointments.

Results

A total of 1009 elective soft tissue hand surgeries at MRVAMC were reviewed. The patients median age was 61 years. Patients included 173 women (17.1%) and 836 men (82.9%). Eighty-one patients (8.0%) returned for unplanned visits. Age (P = .82); proximity to MRVAMC (P = .34); and diabetes (P = .60), smoking (P = .55), anxiety (P = .33), or PTSD (P = .37) were not statistically significant predictors of unplanned appointments. Depression diagnosis (P = .04) and female sex (P = .03) were found to be independent risk factors for an unplanned appointment (Table 1). The most common indication for the requested appointment was pain-related, followed closely by noninfectious wound concerns and persistent symptoms (Table 2).

Discussion

Improved access, quality, and efficiency for patients are goals for the VA.^1-3 The MRVAMC Plastic and Hand Surgery service provides care for the NFSGVAHS and receives an average of 15 to 20 consultation requests daily. The Veterans Health Administration is frequently challenged by staff shortages, and surgical services struggle to respond to consultation requests and treat patients within reasonable time frames.^4,5

The objective of this study was to identify risk factors for unplanned postoperative appointments following elective hand surgery. Unplanned appointments prevent scheduled patients from being seen on time and contribute to backlogs and delays. When patients schedule multiple appointments on the same day, delays in the first clinic’s scheduled appointments create delays for the second and third clinics. Hand surgery clinics can provide a better experience for patients and staff by identifying and mitigating factors prompting unplanned visits.

We anticipated that wound complications would prompt unscheduled visits. Diabetes is a known risk factor for wound healing complications after plastic and hand surgery.^6,7 A hemoglobin A_1c (HbA_1c) screening protocol used by the NFSGVAHS plastic surgery service since 2015 to identify poorly controlled patients with diabetes before surgery may partially explain this finding.⁸ We did not find a statistically significant difference between patients with diabetes and patients without diabetes for scheduling unplanned appointments. The plastic surgery service does not perform elective hand surgery unless the patient’s HbA_1c level is < 9%, or violate the flexor sheath unless HbA_1c level is < 8%. However, Zhuang et al found an increase in soft tissue infections after hand surgery with HbA_1c levels ≥ 7%.⁹

Smoking is a potential factor in postoperative hand surgery complications.^10,11 Lans et al found an increased incidence of 30-day emergency room visits in current and former smokers after outpatient upper extremity fracture surgery.¹² The MRVAMC Plastic Surgery Service counsels patients about the risk of skin necrosis and delayed wound healing, but does not cancel cases or obtain laboratory values to verify abstinence in patients undergoing hand surgery. The VA has multiple resources available for patients interested in smoking cessation through mental health services.¹³

MRVAMC patients have been known to resist returning for scheduled appointments due to the costs or availability of transportation. We suspected that patients who lived further from MRVAMC would be less likely to return for unscheduled visits. We used the first 3 digits of the patients’ mailing zip code to estimate residential proximity to MRVAMC. An acknowledged limitation to this approach is that some veterans have primary addresses in other regions but still spend significant time in the MRVAMC catchment area and use the facility for their health care during the winter months. These “snowbirds” might reside near the facility despite having official addresses that are more distant. Additionally, there was no increased risk of unplanned visits after hand surgery in patients aged > 61 years (the median age of study participants) (P = .82). Dependence on a third party for transportation in older veterans could impact this finding.

Based on the observation that most patients needed reassurance rather than an intervention when they returned for unscheduled appointments, diagnoses of depression, anxiety, and PTSD were evaluated as separate predictive factors. In previous research, anxiety was found to be a risk factor for problematic recovery following carpal tunnel surgery.¹⁴ In the current study, depression was found to be a statistically significant predictor of unscheduled postoperative appointments (P = .04), while anxiety (P = .33) and PTSD (P = .37) were not statistically significant predictors. This is consistent with other studies that have found preexisting depression can predict complications after hand surgery.^15,16 Vranceanu et al found that depression predicted pain intensity and disability after elective hand surgery.¹⁶ Similarly, Oflazoglu et al found a 12% incidence of depression based on the Patient Health Questionnaire-9 in new and returning hand patients who presented to an academic practice.¹⁷ They suggest patients should be assessed at all levels of care and that those with poor responses to surgical or nonsurgical management should be evaluated for depression. MRVAMC has a large mental health service consisting of psychiatrists, psychologists, addiction specialists, social workers, and homeless outreach, and patients tend to already have a diagnosis and mental health practitioner when they present to the clinic.

Recent studies found that wound problems, pain, and stiffness were the most common reasons for return visits.^18,19 Shetty et al identified younger age, worse preoperative pain scores, and poor access to transportation as predictors of preventable emergency room visits, which generate higher health care expenditures than an office visit.¹⁹ Our study’s top reasons for appointments (pain, wound/scar concerns, persistent symptoms) can be addressed with additional presurgery patient and family education. Additionally, clinicians encourage nonnarcotic pain management strategies including anti-inflammatories, acetaminophen, elevation, splinting, and hand therapy, and the hospital employs experienced, fellowship-trained anesthesia block faculty who help limit perioperative narcotic use. Patients are advised that pain can be used to guide them through the postoperative recovery by preventing overuse and alerting them to a problem that would be masked with narcotics, and long-standing problems such as chronic nerve compressions may continue to cause pain after surgery.

Patients and families can be given consistent and repetitive verbal and written information, instructions, and expectations at the initial consultation, preoperative appointment, and on the day of surgery. Postoperatively, outside their scheduled appointments, patients are encouraged to use the My HealtheVet secure messaging system or call the clinic to access an experienced registered nurse before making a long drive. Access to virtual or phone visits can reduce emergent in-person visits in a VA population.²⁰

Ozdag et al found that 42% of patients who had elective carpal tunnel surgery made unplanned electronic messages or phone contact within 2 weeks postsurgery. The authors point out the uncompensated administrative burden on the staff answering these messages and suggest pre-empting the contacts with more up-front education regarding postoperative pain expectations and management strategies.²¹

Fisher et al found that attending hand therapy reduced the number of emergency department visits in postoperative infection cases.²² At MRVAMC, a postoperative emergency department visit for a patient prompts an urgent unplanned appointment to the plastic surgery clinic, often on the same day. The MRVAMC occupational therapy clinic employed 3 on-site certified hand therapists during the study period. Because all hand surgery patients at the clinic receive hand therapy on the same day as their first postoperative appointment, attendance at hand therapy was not evaluated as a predictor of unplanned visits. Scheduled hand therapy is another point of contact where the clinic can provide reassurance and patient education.

While females made up 17.1% of the patients in this study, they constituted 12.5% of all veterans in Florida in fiscal year 2023.²³ This study found that women were more likely to present for unplanned postoperative appointments (P = .03). This is consistent with existing literature which has found that women are higher users of health care and office-based appointments.^24,25 This finding suggests the need for further study into whether our methods of communicating instructions to female patients undergoing plastic surgery may not be optimal.

Strengths and Limitations

As a retrospective review, the authors used information documented by multiple different health care practitioners, including trainees. The electronic medical record problem lists and templates provide consistency of information; however, less seasoned clinicians may interpret what they see and hear differently from more experienced clinicians in the postoperative setting. This study occurred in one part of the country with demographics that may not mirror other VA systems or the general population. The authors hope this study can be a starting point for other health care facilities to investigate ways to minimize the burden of unscheduled appointments. A strength of the study is that it was conducted within a closed system, as patients tend to stay within the VA system and documentation and communication among clinicians, even outside the immediate facility, are easily accessed through the electronic health record.

Conclusions

This study found that depression diagnosis and female sex are statistically significant predictors of unplanned postoperative visits after elective soft tissue hand surgery. More effective patient education during the preoperative period, particularly in patients with depression, may be warranted.

Patients make unplanned appointments after elective soft tissue hand surgery for real or perceived complications when they experience pain, anxiety, or fear. Unplanned appointments can create travel and financial burdens for patients and families. These appointments take time away from scheduled appointments and can contribute to late arrivals and delays in other clinics. Unscheduled appointments contribute to poor access when staff are diverted from scheduled appointments. If predictive factors can be identified, unplanned appointments may either be ameliorated or avoided with better perioperative risk management or education.

Methods

The US Department of Veterans Affairs (VA) North Florida/South Georgia Veterans Health System (NFSGVAHS) and University of Florida Institutional Review Board approved a retrospective chart review of all plastic surgery cases performed at the Malcom Randall VA Medical Center (MRVAMC) and Lake City VAMC operating rooms from July 1, 2018, through December 31, 2019, and January 1, 2021, through June 30, 2022 (nonurgent surgeries were discouraged during the COVID-19 pandemic). Elective soft tissue hand surgery cases were identified based on the operative description found in the Surgical Service Surgeon Staffing Report reviewed monthly by the Service Chief. Potential indicators of unplanned visits were recorded, including age; sex; diagnosis of diabetes, depression, anxiety, or posttraumatic stress disorder (PTSD); current smoking status; and residential zip code. We used the first 3 digits of the patients’ zip codes, which indicate region, as an estimate of proximity to the MRVAMC, which has a 50-county catchment area across North Florida and South Georgia. Diagnoses were found on the “problem list” from the electronic health record documented in the history and physical examinations before surgery. Clinic notes were examined for 3 months postsurgery to identify unplanned postoperative visits and the reason for the appointment. A χ² analysis was conducted using Excel Version 2402. P < .05 was used to determine whether age (> 60 years), sex, proximity to MRVAMC, diabetes, smoking, depression, anxiety, or PTSD were statistically significant independent risk factors for these appointments.

Results

A total of 1009 elective soft tissue hand surgeries at MRVAMC were reviewed. The patients median age was 61 years. Patients included 173 women (17.1%) and 836 men (82.9%). Eighty-one patients (8.0%) returned for unplanned visits. Age (P = .82); proximity to MRVAMC (P = .34); and diabetes (P = .60), smoking (P = .55), anxiety (P = .33), or PTSD (P = .37) were not statistically significant predictors of unplanned appointments. Depression diagnosis (P = .04) and female sex (P = .03) were found to be independent risk factors for an unplanned appointment (Table 1). The most common indication for the requested appointment was pain-related, followed closely by noninfectious wound concerns and persistent symptoms (Table 2).

Discussion

Improved access, quality, and efficiency for patients are goals for the VA.^1-3 The MRVAMC Plastic and Hand Surgery service provides care for the NFSGVAHS and receives an average of 15 to 20 consultation requests daily. The Veterans Health Administration is frequently challenged by staff shortages, and surgical services struggle to respond to consultation requests and treat patients within reasonable time frames.^4,5

The objective of this study was to identify risk factors for unplanned postoperative appointments following elective hand surgery. Unplanned appointments prevent scheduled patients from being seen on time and contribute to backlogs and delays. When patients schedule multiple appointments on the same day, delays in the first clinic’s scheduled appointments create delays for the second and third clinics. Hand surgery clinics can provide a better experience for patients and staff by identifying and mitigating factors prompting unplanned visits.

We anticipated that wound complications would prompt unscheduled visits. Diabetes is a known risk factor for wound healing complications after plastic and hand surgery.^6,7 A hemoglobin A_1c (HbA_1c) screening protocol used by the NFSGVAHS plastic surgery service since 2015 to identify poorly controlled patients with diabetes before surgery may partially explain this finding.⁸ We did not find a statistically significant difference between patients with diabetes and patients without diabetes for scheduling unplanned appointments. The plastic surgery service does not perform elective hand surgery unless the patient’s HbA_1c level is < 9%, or violate the flexor sheath unless HbA_1c level is < 8%. However, Zhuang et al found an increase in soft tissue infections after hand surgery with HbA_1c levels ≥ 7%.⁹

Smoking is a potential factor in postoperative hand surgery complications.^10,11 Lans et al found an increased incidence of 30-day emergency room visits in current and former smokers after outpatient upper extremity fracture surgery.¹² The MRVAMC Plastic Surgery Service counsels patients about the risk of skin necrosis and delayed wound healing, but does not cancel cases or obtain laboratory values to verify abstinence in patients undergoing hand surgery. The VA has multiple resources available for patients interested in smoking cessation through mental health services.¹³

MRVAMC patients have been known to resist returning for scheduled appointments due to the costs or availability of transportation. We suspected that patients who lived further from MRVAMC would be less likely to return for unscheduled visits. We used the first 3 digits of the patients’ mailing zip code to estimate residential proximity to MRVAMC. An acknowledged limitation to this approach is that some veterans have primary addresses in other regions but still spend significant time in the MRVAMC catchment area and use the facility for their health care during the winter months. These “snowbirds” might reside near the facility despite having official addresses that are more distant. Additionally, there was no increased risk of unplanned visits after hand surgery in patients aged > 61 years (the median age of study participants) (P = .82). Dependence on a third party for transportation in older veterans could impact this finding.

Based on the observation that most patients needed reassurance rather than an intervention when they returned for unscheduled appointments, diagnoses of depression, anxiety, and PTSD were evaluated as separate predictive factors. In previous research, anxiety was found to be a risk factor for problematic recovery following carpal tunnel surgery.¹⁴ In the current study, depression was found to be a statistically significant predictor of unscheduled postoperative appointments (P = .04), while anxiety (P = .33) and PTSD (P = .37) were not statistically significant predictors. This is consistent with other studies that have found preexisting depression can predict complications after hand surgery.^15,16 Vranceanu et al found that depression predicted pain intensity and disability after elective hand surgery.¹⁶ Similarly, Oflazoglu et al found a 12% incidence of depression based on the Patient Health Questionnaire-9 in new and returning hand patients who presented to an academic practice.¹⁷ They suggest patients should be assessed at all levels of care and that those with poor responses to surgical or nonsurgical management should be evaluated for depression. MRVAMC has a large mental health service consisting of psychiatrists, psychologists, addiction specialists, social workers, and homeless outreach, and patients tend to already have a diagnosis and mental health practitioner when they present to the clinic.

Recent studies found that wound problems, pain, and stiffness were the most common reasons for return visits.^18,19 Shetty et al identified younger age, worse preoperative pain scores, and poor access to transportation as predictors of preventable emergency room visits, which generate higher health care expenditures than an office visit.¹⁹ Our study’s top reasons for appointments (pain, wound/scar concerns, persistent symptoms) can be addressed with additional presurgery patient and family education. Additionally, clinicians encourage nonnarcotic pain management strategies including anti-inflammatories, acetaminophen, elevation, splinting, and hand therapy, and the hospital employs experienced, fellowship-trained anesthesia block faculty who help limit perioperative narcotic use. Patients are advised that pain can be used to guide them through the postoperative recovery by preventing overuse and alerting them to a problem that would be masked with narcotics, and long-standing problems such as chronic nerve compressions may continue to cause pain after surgery.

Patients and families can be given consistent and repetitive verbal and written information, instructions, and expectations at the initial consultation, preoperative appointment, and on the day of surgery. Postoperatively, outside their scheduled appointments, patients are encouraged to use the My HealtheVet secure messaging system or call the clinic to access an experienced registered nurse before making a long drive. Access to virtual or phone visits can reduce emergent in-person visits in a VA population.²⁰

Ozdag et al found that 42% of patients who had elective carpal tunnel surgery made unplanned electronic messages or phone contact within 2 weeks postsurgery. The authors point out the uncompensated administrative burden on the staff answering these messages and suggest pre-empting the contacts with more up-front education regarding postoperative pain expectations and management strategies.²¹

Fisher et al found that attending hand therapy reduced the number of emergency department visits in postoperative infection cases.²² At MRVAMC, a postoperative emergency department visit for a patient prompts an urgent unplanned appointment to the plastic surgery clinic, often on the same day. The MRVAMC occupational therapy clinic employed 3 on-site certified hand therapists during the study period. Because all hand surgery patients at the clinic receive hand therapy on the same day as their first postoperative appointment, attendance at hand therapy was not evaluated as a predictor of unplanned visits. Scheduled hand therapy is another point of contact where the clinic can provide reassurance and patient education.

While females made up 17.1% of the patients in this study, they constituted 12.5% of all veterans in Florida in fiscal year 2023.²³ This study found that women were more likely to present for unplanned postoperative appointments (P = .03). This is consistent with existing literature which has found that women are higher users of health care and office-based appointments.^24,25 This finding suggests the need for further study into whether our methods of communicating instructions to female patients undergoing plastic surgery may not be optimal.

Strengths and Limitations

As a retrospective review, the authors used information documented by multiple different health care practitioners, including trainees. The electronic medical record problem lists and templates provide consistency of information; however, less seasoned clinicians may interpret what they see and hear differently from more experienced clinicians in the postoperative setting. This study occurred in one part of the country with demographics that may not mirror other VA systems or the general population. The authors hope this study can be a starting point for other health care facilities to investigate ways to minimize the burden of unscheduled appointments. A strength of the study is that it was conducted within a closed system, as patients tend to stay within the VA system and documentation and communication among clinicians, even outside the immediate facility, are easily accessed through the electronic health record.

Conclusions

This study found that depression diagnosis and female sex are statistically significant predictors of unplanned postoperative visits after elective soft tissue hand surgery. More effective patient education during the preoperative period, particularly in patients with depression, may be warranted.

Patients make unplanned appointments after elective soft tissue hand surgery for real or perceived complications when they experience pain, anxiety, or fear. Unplanned appointments can create travel and financial burdens for patients and families. These appointments take time away from scheduled appointments and can contribute to late arrivals and delays in other clinics. Unscheduled appointments contribute to poor access when staff are diverted from scheduled appointments. If predictive factors can be identified, unplanned appointments may either be ameliorated or avoided with better perioperative risk management or education.

Methods

The US Department of Veterans Affairs (VA) North Florida/South Georgia Veterans Health System (NFSGVAHS) and University of Florida Institutional Review Board approved a retrospective chart review of all plastic surgery cases performed at the Malcom Randall VA Medical Center (MRVAMC) and Lake City VAMC operating rooms from July 1, 2018, through December 31, 2019, and January 1, 2021, through June 30, 2022 (nonurgent surgeries were discouraged during the COVID-19 pandemic). Elective soft tissue hand surgery cases were identified based on the operative description found in the Surgical Service Surgeon Staffing Report reviewed monthly by the Service Chief. Potential indicators of unplanned visits were recorded, including age; sex; diagnosis of diabetes, depression, anxiety, or posttraumatic stress disorder (PTSD); current smoking status; and residential zip code. We used the first 3 digits of the patients’ zip codes, which indicate region, as an estimate of proximity to the MRVAMC, which has a 50-county catchment area across North Florida and South Georgia. Diagnoses were found on the “problem list” from the electronic health record documented in the history and physical examinations before surgery. Clinic notes were examined for 3 months postsurgery to identify unplanned postoperative visits and the reason for the appointment. A χ² analysis was conducted using Excel Version 2402. P < .05 was used to determine whether age (> 60 years), sex, proximity to MRVAMC, diabetes, smoking, depression, anxiety, or PTSD were statistically significant independent risk factors for these appointments.

Results

A total of 1009 elective soft tissue hand surgeries at MRVAMC were reviewed. The patients median age was 61 years. Patients included 173 women (17.1%) and 836 men (82.9%). Eighty-one patients (8.0%) returned for unplanned visits. Age (P = .82); proximity to MRVAMC (P = .34); and diabetes (P = .60), smoking (P = .55), anxiety (P = .33), or PTSD (P = .37) were not statistically significant predictors of unplanned appointments. Depression diagnosis (P = .04) and female sex (P = .03) were found to be independent risk factors for an unplanned appointment (Table 1). The most common indication for the requested appointment was pain-related, followed closely by noninfectious wound concerns and persistent symptoms (Table 2).

Discussion

Improved access, quality, and efficiency for patients are goals for the VA.^1-3 The MRVAMC Plastic and Hand Surgery service provides care for the NFSGVAHS and receives an average of 15 to 20 consultation requests daily. The Veterans Health Administration is frequently challenged by staff shortages, and surgical services struggle to respond to consultation requests and treat patients within reasonable time frames.^4,5

The objective of this study was to identify risk factors for unplanned postoperative appointments following elective hand surgery. Unplanned appointments prevent scheduled patients from being seen on time and contribute to backlogs and delays. When patients schedule multiple appointments on the same day, delays in the first clinic’s scheduled appointments create delays for the second and third clinics. Hand surgery clinics can provide a better experience for patients and staff by identifying and mitigating factors prompting unplanned visits.

We anticipated that wound complications would prompt unscheduled visits. Diabetes is a known risk factor for wound healing complications after plastic and hand surgery.^6,7 A hemoglobin A_1c (HbA_1c) screening protocol used by the NFSGVAHS plastic surgery service since 2015 to identify poorly controlled patients with diabetes before surgery may partially explain this finding.⁸ We did not find a statistically significant difference between patients with diabetes and patients without diabetes for scheduling unplanned appointments. The plastic surgery service does not perform elective hand surgery unless the patient’s HbA_1c level is < 9%, or violate the flexor sheath unless HbA_1c level is < 8%. However, Zhuang et al found an increase in soft tissue infections after hand surgery with HbA_1c levels ≥ 7%.⁹

Smoking is a potential factor in postoperative hand surgery complications.^10,11 Lans et al found an increased incidence of 30-day emergency room visits in current and former smokers after outpatient upper extremity fracture surgery.¹² The MRVAMC Plastic Surgery Service counsels patients about the risk of skin necrosis and delayed wound healing, but does not cancel cases or obtain laboratory values to verify abstinence in patients undergoing hand surgery. The VA has multiple resources available for patients interested in smoking cessation through mental health services.¹³

MRVAMC patients have been known to resist returning for scheduled appointments due to the costs or availability of transportation. We suspected that patients who lived further from MRVAMC would be less likely to return for unscheduled visits. We used the first 3 digits of the patients’ mailing zip code to estimate residential proximity to MRVAMC. An acknowledged limitation to this approach is that some veterans have primary addresses in other regions but still spend significant time in the MRVAMC catchment area and use the facility for their health care during the winter months. These “snowbirds” might reside near the facility despite having official addresses that are more distant. Additionally, there was no increased risk of unplanned visits after hand surgery in patients aged > 61 years (the median age of study participants) (P = .82). Dependence on a third party for transportation in older veterans could impact this finding.

Based on the observation that most patients needed reassurance rather than an intervention when they returned for unscheduled appointments, diagnoses of depression, anxiety, and PTSD were evaluated as separate predictive factors. In previous research, anxiety was found to be a risk factor for problematic recovery following carpal tunnel surgery.¹⁴ In the current study, depression was found to be a statistically significant predictor of unscheduled postoperative appointments (P = .04), while anxiety (P = .33) and PTSD (P = .37) were not statistically significant predictors. This is consistent with other studies that have found preexisting depression can predict complications after hand surgery.^15,16 Vranceanu et al found that depression predicted pain intensity and disability after elective hand surgery.¹⁶ Similarly, Oflazoglu et al found a 12% incidence of depression based on the Patient Health Questionnaire-9 in new and returning hand patients who presented to an academic practice.¹⁷ They suggest patients should be assessed at all levels of care and that those with poor responses to surgical or nonsurgical management should be evaluated for depression. MRVAMC has a large mental health service consisting of psychiatrists, psychologists, addiction specialists, social workers, and homeless outreach, and patients tend to already have a diagnosis and mental health practitioner when they present to the clinic.

Recent studies found that wound problems, pain, and stiffness were the most common reasons for return visits.^18,19 Shetty et al identified younger age, worse preoperative pain scores, and poor access to transportation as predictors of preventable emergency room visits, which generate higher health care expenditures than an office visit.¹⁹ Our study’s top reasons for appointments (pain, wound/scar concerns, persistent symptoms) can be addressed with additional presurgery patient and family education. Additionally, clinicians encourage nonnarcotic pain management strategies including anti-inflammatories, acetaminophen, elevation, splinting, and hand therapy, and the hospital employs experienced, fellowship-trained anesthesia block faculty who help limit perioperative narcotic use. Patients are advised that pain can be used to guide them through the postoperative recovery by preventing overuse and alerting them to a problem that would be masked with narcotics, and long-standing problems such as chronic nerve compressions may continue to cause pain after surgery.

Patients and families can be given consistent and repetitive verbal and written information, instructions, and expectations at the initial consultation, preoperative appointment, and on the day of surgery. Postoperatively, outside their scheduled appointments, patients are encouraged to use the My HealtheVet secure messaging system or call the clinic to access an experienced registered nurse before making a long drive. Access to virtual or phone visits can reduce emergent in-person visits in a VA population.²⁰

Ozdag et al found that 42% of patients who had elective carpal tunnel surgery made unplanned electronic messages or phone contact within 2 weeks postsurgery. The authors point out the uncompensated administrative burden on the staff answering these messages and suggest pre-empting the contacts with more up-front education regarding postoperative pain expectations and management strategies.²¹

Fisher et al found that attending hand therapy reduced the number of emergency department visits in postoperative infection cases.²² At MRVAMC, a postoperative emergency department visit for a patient prompts an urgent unplanned appointment to the plastic surgery clinic, often on the same day. The MRVAMC occupational therapy clinic employed 3 on-site certified hand therapists during the study period. Because all hand surgery patients at the clinic receive hand therapy on the same day as their first postoperative appointment, attendance at hand therapy was not evaluated as a predictor of unplanned visits. Scheduled hand therapy is another point of contact where the clinic can provide reassurance and patient education.

While females made up 17.1% of the patients in this study, they constituted 12.5% of all veterans in Florida in fiscal year 2023.²³ This study found that women were more likely to present for unplanned postoperative appointments (P = .03). This is consistent with existing literature which has found that women are higher users of health care and office-based appointments.^24,25 This finding suggests the need for further study into whether our methods of communicating instructions to female patients undergoing plastic surgery may not be optimal.

Strengths and Limitations

As a retrospective review, the authors used information documented by multiple different health care practitioners, including trainees. The electronic medical record problem lists and templates provide consistency of information; however, less seasoned clinicians may interpret what they see and hear differently from more experienced clinicians in the postoperative setting. This study occurred in one part of the country with demographics that may not mirror other VA systems or the general population. The authors hope this study can be a starting point for other health care facilities to investigate ways to minimize the burden of unscheduled appointments. A strength of the study is that it was conducted within a closed system, as patients tend to stay within the VA system and documentation and communication among clinicians, even outside the immediate facility, are easily accessed through the electronic health record.

Conclusions

This study found that depression diagnosis and female sex are statistically significant predictors of unplanned postoperative visits after elective soft tissue hand surgery. More effective patient education during the preoperative period, particularly in patients with depression, may be warranted.

TOPLINE:

In a meta-analysis, patients with hidradenitis suppurativa (HS) faced a more than 80% higher risk for cancer overall than the general population, with particularly elevated risks for gastrointestinal, head and neck, hematologic, and respiratory system cancers.

METHODOLOGY:

• Researchers conducted a meta-analysis including 11 studies from PubMed, Embase, and Web of Science databases published between 2001 and 2024; these studies examined the risk for cancer in patients with HS compared with that in the general population.
• These studies included 624,721 patients diagnosed with HS (mean age, 33.6-43.8 years) and 393,691,636 control individuals from the general population.
• Researchers performed an inverse variance-weighted random-effects analysis to calculate pooled odds ratios (ORs) for cancer overall and specific cancer subtypes.
• Cancer types were categorized into 11 groups for subgroup analysis: bone and soft tissue cancers, breast cancer, central nervous system cancers, endocrine-related cancers, gastrointestinal cancers, head and neck cancers, hematologic cancers, respiratory system cancers, skin cancers, urogenital cancers, and unspecified cancers.

TAKEAWAY:

• Patients with HS demonstrated a significantly higher risk for cancer overall than control individuals (crude OR, 1.82; P = .018).
• Patients with HS showed an increased risk for gastrointestinal cancers (crude OR, 1.61; P = .0002), head and neck cancers (crude OR, 2.41; P = .00001), hematologic cancers (crude OR, 1.71; P = .00005), and respiratory system cancers (crude OR, 1.81; P = .04).
• Patients with HS demonstrated significantly elevated risks for both Hodgkin lymphoma (OR, 2.44; P = .0001) and non-Hodgkin lymphoma (OR, 1.15; P = .012).
• A non-significant increased risk for skin cancer was observed in patients with HS (crude OR, 1.48; P = .08). No increased risks for bone and soft tissue cancers, central nervous system cancers, breast cancer, or urogenital cancers were observed in patients with HS.

IN PRACTICE:

"HS was associated with an increased overall risk of cancer, including several specific subtypes, compared with controls," the authors wrote, suggesting that "studies are adjusting for confounders and assess long-term associations between HS and cancer risk are highly needed to investigate which factors contribute to this cancer risk."

SOURCE:

This study was led by Daniel Isufi, Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. It was published online on March 11, 2026, in Dermatology and Therapy.

LIMITATIONS:

Limited data on cancer subtypes hindered meta-analyses of rare cancers, and the lack of reporting on anti‑inflammatory treatment and disease severity prevented subgroup analyses. Most studies originated from North America, introducing potential geographic bias. No study reported BMI, and ethnicity was poorly documented. Only few studies adjusted for key confounders (smoking, obesity, and alcohol intake), limiting the determination of whether the increased risk for cancer was due to HS itself or shared lifestyle and metabolic factors.

DISCLOSURES:

This study did not receive any funding or sponsorship. Two authors reported receiving research grant funding from the LEO Foundation and having other ties with various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

In a meta-analysis, patients with hidradenitis suppurativa (HS) faced a more than 80% higher risk for cancer overall than the general population, with particularly elevated risks for gastrointestinal, head and neck, hematologic, and respiratory system cancers.

METHODOLOGY:

• Researchers conducted a meta-analysis including 11 studies from PubMed, Embase, and Web of Science databases published between 2001 and 2024; these studies examined the risk for cancer in patients with HS compared with that in the general population.
• These studies included 624,721 patients diagnosed with HS (mean age, 33.6-43.8 years) and 393,691,636 control individuals from the general population.
• Researchers performed an inverse variance-weighted random-effects analysis to calculate pooled odds ratios (ORs) for cancer overall and specific cancer subtypes.
• Cancer types were categorized into 11 groups for subgroup analysis: bone and soft tissue cancers, breast cancer, central nervous system cancers, endocrine-related cancers, gastrointestinal cancers, head and neck cancers, hematologic cancers, respiratory system cancers, skin cancers, urogenital cancers, and unspecified cancers.

TAKEAWAY:

• Patients with HS demonstrated a significantly higher risk for cancer overall than control individuals (crude OR, 1.82; P = .018).
• Patients with HS showed an increased risk for gastrointestinal cancers (crude OR, 1.61; P = .0002), head and neck cancers (crude OR, 2.41; P = .00001), hematologic cancers (crude OR, 1.71; P = .00005), and respiratory system cancers (crude OR, 1.81; P = .04).
• Patients with HS demonstrated significantly elevated risks for both Hodgkin lymphoma (OR, 2.44; P = .0001) and non-Hodgkin lymphoma (OR, 1.15; P = .012).
• A non-significant increased risk for skin cancer was observed in patients with HS (crude OR, 1.48; P = .08). No increased risks for bone and soft tissue cancers, central nervous system cancers, breast cancer, or urogenital cancers were observed in patients with HS.

IN PRACTICE:

"HS was associated with an increased overall risk of cancer, including several specific subtypes, compared with controls," the authors wrote, suggesting that "studies are adjusting for confounders and assess long-term associations between HS and cancer risk are highly needed to investigate which factors contribute to this cancer risk."

SOURCE:

This study was led by Daniel Isufi, Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. It was published online on March 11, 2026, in Dermatology and Therapy.

LIMITATIONS:

Limited data on cancer subtypes hindered meta-analyses of rare cancers, and the lack of reporting on anti‑inflammatory treatment and disease severity prevented subgroup analyses. Most studies originated from North America, introducing potential geographic bias. No study reported BMI, and ethnicity was poorly documented. Only few studies adjusted for key confounders (smoking, obesity, and alcohol intake), limiting the determination of whether the increased risk for cancer was due to HS itself or shared lifestyle and metabolic factors.

DISCLOSURES:

This study did not receive any funding or sponsorship. Two authors reported receiving research grant funding from the LEO Foundation and having other ties with various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

In a meta-analysis, patients with hidradenitis suppurativa (HS) faced a more than 80% higher risk for cancer overall than the general population, with particularly elevated risks for gastrointestinal, head and neck, hematologic, and respiratory system cancers.

METHODOLOGY:

• Researchers conducted a meta-analysis including 11 studies from PubMed, Embase, and Web of Science databases published between 2001 and 2024; these studies examined the risk for cancer in patients with HS compared with that in the general population.
• These studies included 624,721 patients diagnosed with HS (mean age, 33.6-43.8 years) and 393,691,636 control individuals from the general population.
• Researchers performed an inverse variance-weighted random-effects analysis to calculate pooled odds ratios (ORs) for cancer overall and specific cancer subtypes.
• Cancer types were categorized into 11 groups for subgroup analysis: bone and soft tissue cancers, breast cancer, central nervous system cancers, endocrine-related cancers, gastrointestinal cancers, head and neck cancers, hematologic cancers, respiratory system cancers, skin cancers, urogenital cancers, and unspecified cancers.

TAKEAWAY:

• Patients with HS demonstrated a significantly higher risk for cancer overall than control individuals (crude OR, 1.82; P = .018).
• Patients with HS showed an increased risk for gastrointestinal cancers (crude OR, 1.61; P = .0002), head and neck cancers (crude OR, 2.41; P = .00001), hematologic cancers (crude OR, 1.71; P = .00005), and respiratory system cancers (crude OR, 1.81; P = .04).
• Patients with HS demonstrated significantly elevated risks for both Hodgkin lymphoma (OR, 2.44; P = .0001) and non-Hodgkin lymphoma (OR, 1.15; P = .012).
• A non-significant increased risk for skin cancer was observed in patients with HS (crude OR, 1.48; P = .08). No increased risks for bone and soft tissue cancers, central nervous system cancers, breast cancer, or urogenital cancers were observed in patients with HS.

IN PRACTICE:

"HS was associated with an increased overall risk of cancer, including several specific subtypes, compared with controls," the authors wrote, suggesting that "studies are adjusting for confounders and assess long-term associations between HS and cancer risk are highly needed to investigate which factors contribute to this cancer risk."

SOURCE:

This study was led by Daniel Isufi, Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. It was published online on March 11, 2026, in Dermatology and Therapy.

LIMITATIONS:

Limited data on cancer subtypes hindered meta-analyses of rare cancers, and the lack of reporting on anti‑inflammatory treatment and disease severity prevented subgroup analyses. Most studies originated from North America, introducing potential geographic bias. No study reported BMI, and ethnicity was poorly documented. Only few studies adjusted for key confounders (smoking, obesity, and alcohol intake), limiting the determination of whether the increased risk for cancer was due to HS itself or shared lifestyle and metabolic factors.

DISCLOSURES:

This study did not receive any funding or sponsorship. Two authors reported receiving research grant funding from the LEO Foundation and having other ties with various other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.