Colon and Rectal

Cold snare endoscopic mucosal resection (EMR) may be a safe therapeutic option for selected large colorectal polyps, thanks to a safety profile superior to that of hot EMR.

In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.

“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”

Evangelisches Diakoniekrankenhaus Freiburg

The Study

From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.

Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).

Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.

Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.

Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).

Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.

Oregon Health & Science University

Implications

This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.

Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”

The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.

“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”

This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Cold snare endoscopic mucosal resection (EMR) may be a safe therapeutic option for selected large colorectal polyps, thanks to a safety profile superior to that of hot EMR.

In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.

“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”

Evangelisches Diakoniekrankenhaus Freiburg

The Study

From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.

Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).

Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.

Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.

Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).

Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.

Oregon Health & Science University

Implications

This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.

Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”

The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.

“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”

This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Cold snare endoscopic mucosal resection (EMR) may be a safe therapeutic option for selected large colorectal polyps, thanks to a safety profile superior to that of hot EMR.

In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.

“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”

Evangelisches Diakoniekrankenhaus Freiburg

The Study

From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.

Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).

Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.

Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.

Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).

Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.

Oregon Health & Science University

Implications

This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.

Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”

The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.

“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”

This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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.

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

TOPLINE:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various 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:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various 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:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various 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:

Fecal immunochemical test (FIT) screening reduces colorectal cancer (CRC) mortality by 33% overall, with a notable 42% reduction in deaths from left colon and rectal cancers, new data show.

METHODOLOGY:

• In the United States, annual FIT screening is recommended among average-risk adults to reduce the risk for death from CRC, but evidence on its effectiveness is limited.
• Researchers performed a nested case-control study within two large, demographically diverse health systems with long-standing programs of mailing FITs to promote CRC screening efforts.
• They compared 1103 adults who had died of CRC between 2011 and 2017 (cases) with 9608 matched, randomly selected people who were alive and free of CRC (controls).
• Analyses focused on FIT screening completed within 5 years before CRC diagnosis for cases or the corresponding date for controls.
• The primary outcome measured was CRC death overall and by tumor location; secondary analyses assessed CRC death by race and ethnicity.

TAKEAWAY:

• In regression analysis, completing one or more FIT screenings was associated with a 33% lower risk for CRC death overall.
• There was a 42% lower risk for death from left colon and rectum cancers but no significant reduction in mortality from right colon cancers.
• The benefits of FIT screening were observed across racial and ethnic groups, with significant mortality reductions of 63% in non-Hispanic Asian, 42% in non-Hispanic Black, and 29% in non-Hispanic White individuals.

IN PRACTICE:

“The findings support the use of strategies for coordinated and equitable large-scale population-based delivery of FIT screening with follow-up of abnormal screening results to help avert preventable premature CRC deaths,” the authors wrote.

SOURCE:

The study, with first author Chyke A. Doubeni, MD, MPH, Center for Health Equity, The Ohio State University Wexner Medical Center, Columbus, Ohio, was published online in JAMA Network Open.

LIMITATIONS:

Almost one half of study subjects had completed two or more FITs, but the case-control design was not suitable for assessing the impact of repeated screening. The study was conducted prior to the US Preventive Services Task Force recommendation to start screening at age 45 years, so the findings may not directly apply to adults aged 45-49 years. 

DISCLOSURES:

The study was funded by the National Cancer Institute. Dr. Doubeni reported receiving royalties from UpToDate, and additional authors reported receiving grants outside the submitted work. No other disclosures were reported.

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

TOPLINE:

Fecal immunochemical test (FIT) screening reduces colorectal cancer (CRC) mortality by 33% overall, with a notable 42% reduction in deaths from left colon and rectal cancers, new data show.

METHODOLOGY:

• In the United States, annual FIT screening is recommended among average-risk adults to reduce the risk for death from CRC, but evidence on its effectiveness is limited.
• Researchers performed a nested case-control study within two large, demographically diverse health systems with long-standing programs of mailing FITs to promote CRC screening efforts.
• They compared 1103 adults who had died of CRC between 2011 and 2017 (cases) with 9608 matched, randomly selected people who were alive and free of CRC (controls).
• Analyses focused on FIT screening completed within 5 years before CRC diagnosis for cases or the corresponding date for controls.
• The primary outcome measured was CRC death overall and by tumor location; secondary analyses assessed CRC death by race and ethnicity.

TAKEAWAY:

• In regression analysis, completing one or more FIT screenings was associated with a 33% lower risk for CRC death overall.
• There was a 42% lower risk for death from left colon and rectum cancers but no significant reduction in mortality from right colon cancers.
• The benefits of FIT screening were observed across racial and ethnic groups, with significant mortality reductions of 63% in non-Hispanic Asian, 42% in non-Hispanic Black, and 29% in non-Hispanic White individuals.

IN PRACTICE:

“The findings support the use of strategies for coordinated and equitable large-scale population-based delivery of FIT screening with follow-up of abnormal screening results to help avert preventable premature CRC deaths,” the authors wrote.

SOURCE:

The study, with first author Chyke A. Doubeni, MD, MPH, Center for Health Equity, The Ohio State University Wexner Medical Center, Columbus, Ohio, was published online in JAMA Network Open.

LIMITATIONS:

Almost one half of study subjects had completed two or more FITs, but the case-control design was not suitable for assessing the impact of repeated screening. The study was conducted prior to the US Preventive Services Task Force recommendation to start screening at age 45 years, so the findings may not directly apply to adults aged 45-49 years. 

DISCLOSURES:

The study was funded by the National Cancer Institute. Dr. Doubeni reported receiving royalties from UpToDate, and additional authors reported receiving grants outside the submitted work. No other disclosures were reported.

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

TOPLINE:

Fecal immunochemical test (FIT) screening reduces colorectal cancer (CRC) mortality by 33% overall, with a notable 42% reduction in deaths from left colon and rectal cancers, new data show.

METHODOLOGY:

• In the United States, annual FIT screening is recommended among average-risk adults to reduce the risk for death from CRC, but evidence on its effectiveness is limited.
• Researchers performed a nested case-control study within two large, demographically diverse health systems with long-standing programs of mailing FITs to promote CRC screening efforts.
• They compared 1103 adults who had died of CRC between 2011 and 2017 (cases) with 9608 matched, randomly selected people who were alive and free of CRC (controls).
• Analyses focused on FIT screening completed within 5 years before CRC diagnosis for cases or the corresponding date for controls.
• The primary outcome measured was CRC death overall and by tumor location; secondary analyses assessed CRC death by race and ethnicity.

TAKEAWAY:

• In regression analysis, completing one or more FIT screenings was associated with a 33% lower risk for CRC death overall.
• There was a 42% lower risk for death from left colon and rectum cancers but no significant reduction in mortality from right colon cancers.
• The benefits of FIT screening were observed across racial and ethnic groups, with significant mortality reductions of 63% in non-Hispanic Asian, 42% in non-Hispanic Black, and 29% in non-Hispanic White individuals.

IN PRACTICE:

“The findings support the use of strategies for coordinated and equitable large-scale population-based delivery of FIT screening with follow-up of abnormal screening results to help avert preventable premature CRC deaths,” the authors wrote.

SOURCE:

The study, with first author Chyke A. Doubeni, MD, MPH, Center for Health Equity, The Ohio State University Wexner Medical Center, Columbus, Ohio, was published online in JAMA Network Open.

LIMITATIONS:

Almost one half of study subjects had completed two or more FITs, but the case-control design was not suitable for assessing the impact of repeated screening. The study was conducted prior to the US Preventive Services Task Force recommendation to start screening at age 45 years, so the findings may not directly apply to adults aged 45-49 years. 

DISCLOSURES:

The study was funded by the National Cancer Institute. Dr. Doubeni reported receiving royalties from UpToDate, and additional authors reported receiving grants outside the submitted work. No other disclosures were reported.

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

TOPLINE:

A novel method combining genetic variants, symptoms, and patient characteristics is moderately successful at predicting which primary care patients are at high risk of developing colorectal cancer (CRC) within the next 2 years — without the benefit of a faecal immunochemical test (FIT). Up to 16% of primary care patients are non-compliant with FIT, which is the gold standard for predicting CRC.

METHODOLOGY:

• This study was retrospective cohort of 50,387 UK Biobank participants reporting a CRC symptom in primary care at age ≥ 40 years.
• The novel method, called an integrated risk model, used a combination of a polygenic risk score from genetic testing, symptoms, and patient characteristics to identify patients likely to develop CRC in the next 2 years.
• The primary outcome was the risk model’s performance in classifying a CRC case according to a statistical metric, the receiver operating characteristic area under the curve. Values range from 0 to 1, where 1 indicates perfect discriminative power and 0.5 indicates no discriminative power.

TAKEAWAY:

• The cohort of 50,387 participants was found to have 438 cases of CRC and 49,949 controls without CRC within 2 years of symptom reporting. CRC cases were diagnosed by hospital records, cancer registries, or death records.
• Increased risk of a CRC diagnosis was identified by a combination of six variables: older age at index date of symptom, higher polygenic risk score, which included 201 variants, male sex, previous smoking, rectal bleeding, and change in bowel habit.
• The polygenic risk score alone had good ability to distinguish cases from controls because 1.45% of participants in the highest quintile and 0.42% in the lowest quintile were later diagnosed with CRC.
• The variables were used to calculate an integrated risk model, which estimated the cross-sectional risk (in 80% of the final cohort) of a subsequent CRC diagnosis within 2 years. The highest scoring integrated risk model in this study was found to have a receiver operating characteristic area under the curve value of 0.76 with a 95% CI of 0.71-0.81. (A value of this magnitude indicates moderate discriminative ability to distinguish cases from controls because it falls between 0.7 and 0.8. A higher value [above 0.8] is considered strong and a lower value [< 0.7] is considered weak.)

IN PRACTICE:

The authors concluded, “The [integrated risk model] developed in this study predicts, with good accuracy, which patients presenting with CRC symptoms in a primary care setting are likely to be diagnosed with CRC within the next 2 years.”

The integrated risk model has “potential to be immediately actionable in the clinical setting … [by] inform[ing] patient triage, improving early diagnostic rates and health outcomes and reducing pressure on diagnostic secondary care services.”

SOURCE:

The corresponding author is Harry D. Green of the University of Exeter, England. The study (2024 Aug 1. doi: 10.1038/s41431-024-01654-3) appeared in the European Journal of Human Genetics.

LIMITATIONS:

Limitations included an observational design and the inability of the integrated risk model to outperform FIT, which has a receiver operating characteristic area under the curve of 0.95.

DISCLOSURES:

None of the authors reported competing interests. The funding sources included the National Institute for Health and Care Research and others.

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

TOPLINE:

A novel method combining genetic variants, symptoms, and patient characteristics is moderately successful at predicting which primary care patients are at high risk of developing colorectal cancer (CRC) within the next 2 years — without the benefit of a faecal immunochemical test (FIT). Up to 16% of primary care patients are non-compliant with FIT, which is the gold standard for predicting CRC.

METHODOLOGY:

• This study was retrospective cohort of 50,387 UK Biobank participants reporting a CRC symptom in primary care at age ≥ 40 years.
• The novel method, called an integrated risk model, used a combination of a polygenic risk score from genetic testing, symptoms, and patient characteristics to identify patients likely to develop CRC in the next 2 years.
• The primary outcome was the risk model’s performance in classifying a CRC case according to a statistical metric, the receiver operating characteristic area under the curve. Values range from 0 to 1, where 1 indicates perfect discriminative power and 0.5 indicates no discriminative power.

TAKEAWAY:

• The cohort of 50,387 participants was found to have 438 cases of CRC and 49,949 controls without CRC within 2 years of symptom reporting. CRC cases were diagnosed by hospital records, cancer registries, or death records.
• Increased risk of a CRC diagnosis was identified by a combination of six variables: older age at index date of symptom, higher polygenic risk score, which included 201 variants, male sex, previous smoking, rectal bleeding, and change in bowel habit.
• The polygenic risk score alone had good ability to distinguish cases from controls because 1.45% of participants in the highest quintile and 0.42% in the lowest quintile were later diagnosed with CRC.
• The variables were used to calculate an integrated risk model, which estimated the cross-sectional risk (in 80% of the final cohort) of a subsequent CRC diagnosis within 2 years. The highest scoring integrated risk model in this study was found to have a receiver operating characteristic area under the curve value of 0.76 with a 95% CI of 0.71-0.81. (A value of this magnitude indicates moderate discriminative ability to distinguish cases from controls because it falls between 0.7 and 0.8. A higher value [above 0.8] is considered strong and a lower value [< 0.7] is considered weak.)

IN PRACTICE:

The authors concluded, “The [integrated risk model] developed in this study predicts, with good accuracy, which patients presenting with CRC symptoms in a primary care setting are likely to be diagnosed with CRC within the next 2 years.”

The integrated risk model has “potential to be immediately actionable in the clinical setting … [by] inform[ing] patient triage, improving early diagnostic rates and health outcomes and reducing pressure on diagnostic secondary care services.”

SOURCE:

The corresponding author is Harry D. Green of the University of Exeter, England. The study (2024 Aug 1. doi: 10.1038/s41431-024-01654-3) appeared in the European Journal of Human Genetics.

LIMITATIONS:

Limitations included an observational design and the inability of the integrated risk model to outperform FIT, which has a receiver operating characteristic area under the curve of 0.95.

DISCLOSURES:

None of the authors reported competing interests. The funding sources included the National Institute for Health and Care Research and others.

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

TOPLINE:

A novel method combining genetic variants, symptoms, and patient characteristics is moderately successful at predicting which primary care patients are at high risk of developing colorectal cancer (CRC) within the next 2 years — without the benefit of a faecal immunochemical test (FIT). Up to 16% of primary care patients are non-compliant with FIT, which is the gold standard for predicting CRC.

METHODOLOGY:

• This study was retrospective cohort of 50,387 UK Biobank participants reporting a CRC symptom in primary care at age ≥ 40 years.
• The novel method, called an integrated risk model, used a combination of a polygenic risk score from genetic testing, symptoms, and patient characteristics to identify patients likely to develop CRC in the next 2 years.
• The primary outcome was the risk model’s performance in classifying a CRC case according to a statistical metric, the receiver operating characteristic area under the curve. Values range from 0 to 1, where 1 indicates perfect discriminative power and 0.5 indicates no discriminative power.

TAKEAWAY:

• The cohort of 50,387 participants was found to have 438 cases of CRC and 49,949 controls without CRC within 2 years of symptom reporting. CRC cases were diagnosed by hospital records, cancer registries, or death records.
• Increased risk of a CRC diagnosis was identified by a combination of six variables: older age at index date of symptom, higher polygenic risk score, which included 201 variants, male sex, previous smoking, rectal bleeding, and change in bowel habit.
• The polygenic risk score alone had good ability to distinguish cases from controls because 1.45% of participants in the highest quintile and 0.42% in the lowest quintile were later diagnosed with CRC.
• The variables were used to calculate an integrated risk model, which estimated the cross-sectional risk (in 80% of the final cohort) of a subsequent CRC diagnosis within 2 years. The highest scoring integrated risk model in this study was found to have a receiver operating characteristic area under the curve value of 0.76 with a 95% CI of 0.71-0.81. (A value of this magnitude indicates moderate discriminative ability to distinguish cases from controls because it falls between 0.7 and 0.8. A higher value [above 0.8] is considered strong and a lower value [< 0.7] is considered weak.)

IN PRACTICE:

The authors concluded, “The [integrated risk model] developed in this study predicts, with good accuracy, which patients presenting with CRC symptoms in a primary care setting are likely to be diagnosed with CRC within the next 2 years.”

The integrated risk model has “potential to be immediately actionable in the clinical setting … [by] inform[ing] patient triage, improving early diagnostic rates and health outcomes and reducing pressure on diagnostic secondary care services.”

SOURCE:

The corresponding author is Harry D. Green of the University of Exeter, England. The study (2024 Aug 1. doi: 10.1038/s41431-024-01654-3) appeared in the European Journal of Human Genetics.

LIMITATIONS:

Limitations included an observational design and the inability of the integrated risk model to outperform FIT, which has a receiver operating characteristic area under the curve of 0.95.

DISCLOSURES:

None of the authors reported competing interests. The funding sources included the National Institute for Health and Care Research and others.

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

A new stool-based syndecan-2 methylation (mSDC2) test may improve the detection of colorectal cancer (CRC) and advanced colorectal neoplasia (ACN), based on a prospective, real-world study.

These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.

“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.

The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.

After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.

“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.

A new stool-based syndecan-2 methylation (mSDC2) test may improve the detection of colorectal cancer (CRC) and advanced colorectal neoplasia (ACN), based on a prospective, real-world study.

These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.

“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.

The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.

After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.

“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.

A new stool-based syndecan-2 methylation (mSDC2) test may improve the detection of colorectal cancer (CRC) and advanced colorectal neoplasia (ACN), based on a prospective, real-world study.

These findings suggest that the mSDC2 assay could improve the efficacy and resource utilization of existing screening programs, reported co–lead authors Shengbing Zhao, MD and Zixuan He, MD, of Naval Medical University, Shanghai, China, and colleagues.

“Conventional risk-stratification strategies, such as fecal immunochemical test (FIT) and life risk factors, are still criticized for being inferior at identifying early-stage CRC and ACN, and their real-world performance is probably further weakened by the low annual participation rate and compliance of subsequent colonoscopy,” the investigators wrote in Gastroenterology. Recent case studies have reported “high diagnostic performance” using stool-based testing for mSDC2, which is “the most accurate single-targeted gene” for colorectal neoplasia, according to the investigators; however, real-world outcomes have yet to be demonstrated, prompting the present study. The prospective, multicenter, community-based trial compared the diagnostic performance of the mSDC2 test against FIT and Asia-Pacific Colorectal Screening (APCS) scores.

The primary outcome was detection of ACN. Secondary outcomes included detection of CRC, early-stage CRC, ACN, colorectal neoplasia (CN), and clinically relevant serrated polyp (CRSP). Screening strategies were also compared in terms of cost-effectiveness and impact on colonoscopy workload.The final dataset included 10,360 participants aged 45-75 years who underwent screening between 2020 and 2022.

After determining APCS scores, stool samples were analyzed for mSDC2 and FIT markers. Based on risk stratification results, participants were invited to undergo colonoscopy. A total of 3,381 participants completed colonoscopy, with 1914 from the increased-risk population and 1467 from the average-risk population. Participants who tested positive for mSDC2 had significantly higher detection rates for all measured outcomes than those who tested negative (all, P < .05). For example, the detection rate for ACN was 26.6% in mSDC2-positive participants, compared with 9.3% in mSDC2-negative participants, with a relative risk of 2.87 (95% CI, 2.39-3.44). For CRC, the detection rate was 4.2% in mSDC2-positive participants vs 0.1% in mSDC2-negative participants, yielding a relative risk of 29.73 (95% CI, 10.29-85.91). Performance held steady across subgroups.The mSDC2 test demonstrated cost-effectiveness by significantly reducing the number of colonoscopies needed to detect one case of ACN or CRC. Specifically, the number of colonoscopies needed to screen for ACN and CRC was reduced by 56.2% and 81.5%, respectively. Parallel combinations of mSDC2 with APCS or FIT enhanced both diagnostic performance and cost-effectiveness.

“This study further illustrates that the mSDC2 test consistently improves predictive abilities for CN, CRSP, ACN, and CRC, which is not influenced by subgroups of lesion location or risk factors, even under the risk stratification by FIT or APCS,” the investigators wrote. “The excellent diagnostic ability of mSDC2 in premalignant lesions, early-stage CRC, and early-onset CRC indicates a promising value in early detection and prevention of CRC ... the mSDC2 test or a parallel combination of multiple screening methods might be promising to improve real-world CRC screening performance and reduce colonoscopy workload in community practice.”The study was supported by the National Key Research and Development Program of China, Deep Blue Project of Naval Medical University, the Creative Biosciences, and others. The investigators reported no conflicts of interest.

In late July, the US Food and Drug Administration (FDA) approved the first use of a liquid biopsy (blood test) for colorectal cancer (CRC) screening. The test, called Shield, launched commercially the first week of August and is the first blood test to be approved by the FDA as a primary screening option for CRC that meets requirements for Medicare reimbursement.

While the convenience of a blood test could potentially encourage more people to get screened, expert consensus is that blood tests can’t prevent CRC and should not be considered a replacement for a colonoscopy. Modeling studies and expert consensus published earlier this year in Gastroenterology and in Clinical Gastroenterology and Hepatology shed light on the perils of liquid biopsy.

“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor as cost-effective, and would worsen outcomes,” said David Lieberman, MD, AGAF, chair, AGA CRC Workshop chair and lead author of an expert commentary on liquid biopsy for CRC screening.

Five Key Takeaways

• A blood test for CRC that meets minimal CMS criteria for sensitivity and performed every 3 years would likely result in better outcomes than no screening.
• A blood test for CRC offers a simple process that could encourage more people to participate in screening. Patients who may have declined colonoscopy should understand the need for a colonoscopy if findings are abnormal.
• Because blood tests for CRC are predicted to be less effective and more costly than currently established screening programs, they cannot be recommended to replace established effective screening methods.
• Although blood tests would improve outcomes in currently unscreened people, substituting blood tests for a currently effective test would worsen patient outcomes and increase cost.
• Potential benchmarks that industry might use to assess an effective blood test for CRC going forward would be sensitivity for stage I-III CRC of > 90%, with sensitivity for advanced adenomas of > 40%-50%.

University of California San Diego

“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” said John M. Carethers, MD, AGAF, AGA past president and vice chancellor for health sciences at the University of California San Diego.

In late July, the US Food and Drug Administration (FDA) approved the first use of a liquid biopsy (blood test) for colorectal cancer (CRC) screening. The test, called Shield, launched commercially the first week of August and is the first blood test to be approved by the FDA as a primary screening option for CRC that meets requirements for Medicare reimbursement.

While the convenience of a blood test could potentially encourage more people to get screened, expert consensus is that blood tests can’t prevent CRC and should not be considered a replacement for a colonoscopy. Modeling studies and expert consensus published earlier this year in Gastroenterology and in Clinical Gastroenterology and Hepatology shed light on the perils of liquid biopsy.

“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor as cost-effective, and would worsen outcomes,” said David Lieberman, MD, AGAF, chair, AGA CRC Workshop chair and lead author of an expert commentary on liquid biopsy for CRC screening.

Five Key Takeaways

• A blood test for CRC that meets minimal CMS criteria for sensitivity and performed every 3 years would likely result in better outcomes than no screening.
• A blood test for CRC offers a simple process that could encourage more people to participate in screening. Patients who may have declined colonoscopy should understand the need for a colonoscopy if findings are abnormal.
• Because blood tests for CRC are predicted to be less effective and more costly than currently established screening programs, they cannot be recommended to replace established effective screening methods.
• Although blood tests would improve outcomes in currently unscreened people, substituting blood tests for a currently effective test would worsen patient outcomes and increase cost.
• Potential benchmarks that industry might use to assess an effective blood test for CRC going forward would be sensitivity for stage I-III CRC of > 90%, with sensitivity for advanced adenomas of > 40%-50%.

University of California San Diego

“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” said John M. Carethers, MD, AGAF, AGA past president and vice chancellor for health sciences at the University of California San Diego.

In late July, the US Food and Drug Administration (FDA) approved the first use of a liquid biopsy (blood test) for colorectal cancer (CRC) screening. The test, called Shield, launched commercially the first week of August and is the first blood test to be approved by the FDA as a primary screening option for CRC that meets requirements for Medicare reimbursement.

While the convenience of a blood test could potentially encourage more people to get screened, expert consensus is that blood tests can’t prevent CRC and should not be considered a replacement for a colonoscopy. Modeling studies and expert consensus published earlier this year in Gastroenterology and in Clinical Gastroenterology and Hepatology shed light on the perils of liquid biopsy.

“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor as cost-effective, and would worsen outcomes,” said David Lieberman, MD, AGAF, chair, AGA CRC Workshop chair and lead author of an expert commentary on liquid biopsy for CRC screening.

Five Key Takeaways

• A blood test for CRC that meets minimal CMS criteria for sensitivity and performed every 3 years would likely result in better outcomes than no screening.
• A blood test for CRC offers a simple process that could encourage more people to participate in screening. Patients who may have declined colonoscopy should understand the need for a colonoscopy if findings are abnormal.
• Because blood tests for CRC are predicted to be less effective and more costly than currently established screening programs, they cannot be recommended to replace established effective screening methods.
• Although blood tests would improve outcomes in currently unscreened people, substituting blood tests for a currently effective test would worsen patient outcomes and increase cost.
• Potential benchmarks that industry might use to assess an effective blood test for CRC going forward would be sensitivity for stage I-III CRC of > 90%, with sensitivity for advanced adenomas of > 40%-50%.

University of California San Diego

“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” said John M. Carethers, MD, AGAF, AGA past president and vice chancellor for health sciences at the University of California San Diego.

The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.

He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.

He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.

Dr. Dey, a graduate of the AGA Future Leaders Program, is now a gastroenterologist and researcher at the Fred Hutch Cancer Center in Seattle. In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.

Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.

Fred Hutch Cancer Center

Q: Why did you choose GI?

When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.

As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
 

Q: What role does digestive health play in overall health?

Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.

Q: What practice challenges have you faced in your career?

First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.

Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.

The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.

Q: Have you published other papers?

We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well. 

Q: What is your vision for the future in GI, and in your career?

The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.

Lightning Round

Texting or talking?

Talking

Favorite city in the United States besides the one you live in?

St. Louis

Cat or dog person?

Both

If you weren’t a GI, what would you be?

Musician

Best place you went on vacation?

Borneo

Favorite sport?

Soccer

Favorite ice cream?

Cashew-based salted caramel

What song do you have to sing along with when you hear it?

Sweet Child of Mine

Favorite movie or TV show?

25th Hour or Shawshank Redemption

Optimist or Pessimist?

Optimist

The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.

He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.

He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.

Dr. Dey, a graduate of the AGA Future Leaders Program, is now a gastroenterologist and researcher at the Fred Hutch Cancer Center in Seattle. In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.

Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.

Fred Hutch Cancer Center

Q: Why did you choose GI?

When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.

As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
 

Q: What role does digestive health play in overall health?

Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.

Q: What practice challenges have you faced in your career?

First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.

Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.

The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.

Q: Have you published other papers?

We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well. 

Q: What is your vision for the future in GI, and in your career?

The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.

Lightning Round

Texting or talking?

Talking

Favorite city in the United States besides the one you live in?

St. Louis

Cat or dog person?

Both

If you weren’t a GI, what would you be?

Musician

Best place you went on vacation?

Borneo

Favorite sport?

Soccer

Favorite ice cream?

Cashew-based salted caramel

What song do you have to sing along with when you hear it?

Sweet Child of Mine

Favorite movie or TV show?

25th Hour or Shawshank Redemption

Optimist or Pessimist?

Optimist

The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.

He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.

He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.

Dr. Dey, a graduate of the AGA Future Leaders Program, is now a gastroenterologist and researcher at the Fred Hutch Cancer Center in Seattle. In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.

Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.

Fred Hutch Cancer Center

Q: Why did you choose GI?

When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.

As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
 

Q: What role does digestive health play in overall health?

Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.

Q: What practice challenges have you faced in your career?

First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.

Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.

The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.

Q: Have you published other papers?

We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well. 

Q: What is your vision for the future in GI, and in your career?

The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.

Lightning Round

Texting or talking?

Talking

Favorite city in the United States besides the one you live in?

St. Louis

Cat or dog person?

Both

If you weren’t a GI, what would you be?

Musician

Best place you went on vacation?

Borneo

Favorite sport?

Soccer

Favorite ice cream?

Cashew-based salted caramel

What song do you have to sing along with when you hear it?

Sweet Child of Mine

Favorite movie or TV show?

25th Hour or Shawshank Redemption

Optimist or Pessimist?

Optimist

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.