Jury still out on survival benefit of resecting primary in mCRC

SAN FRANCISCO – Resecting the primary tumor in patients with metastatic colon or colorectal cancer may prolong survival. But then again, it may not.

This was the overarching take-home message from a trio of cohort studies presented at the Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. Results were reported in a poster session.

“Whereas surgery is the primary treatment of localized colorectal cancer, resection of the primary tumor in patients with incurable metastatic disease is usually recommended for palliative purposes to manage obstruction, perforation, or bleeding,” Dr. Shahid Ahmed, lead investigator of one of the studies, noted in comments provided by e-mail. “The role of surgical resection of the primary tumor in patients with newly diagnosed incurable stage IV colorectal cancer remains controversial.”

In earlier research, he and colleagues found a survival benefit of primary resection among Canadian patients whose cancer was diagnosed between 1992 and 2005 (Cancer 2014;120:683-91). But the majority did not receive systemic therapy, and those who did were often given older regimens.

In a new study aimed at testing the association in the contemporary treatment era, the researchers analyzed data from 569 patients with stage IV colorectal cancer diagnosed between 2006 and 2010 who had a median follow-up of 11 months. Overall, 55% had resection of the primary tumor.

Among the 57% of patients who received systemic therapy, 91% received FOLFIRI or FOLFOX, 65% received bevacizumab (Avastin), and 10% received cetuximab (Erbitux) or panitumumab (Vectibix), according to Dr. Ahmed, professor of medicine, University of Saskatchewan, Canada.

Results for the entire cohort showed that median overall survival was 18 months in patients who had resection of their primary versus 4 months in those who did not (multivariate hazard ratio, 0.44; P less than .001).

Among the subgroup of patients who received chemotherapy, median survival was 27 months with primary resection versus 14 months without it (P less than .0001). And among the subgroup that specifically received FOLFIRI or FOLFOX and a biologic agent, it was 35 months with primary resection and 23 months without it (P less than .001).

“Surgical resection of primary tumor improves survival of patients with stage IV colorectal cancer, independent of other prognostic variables including age, performance status, comorbid illness, and chemotherapy,” maintained Dr. Ahmed. “The current study validates our findings and supports surgical resection of primary tumor in patients with stage IV colorectal cancer who are treated with modern chemotherapy and biologics.

“A well-designed prospective randomized trial is warranted to confirm the survival benefit conferred by the primary tumor resection,” he added, noting that two such trials in Europe – SYNCHRONOUS and CAIRO4 – are underway.

“If the magnitude of survival benefit is confirmed in these future randomized studies, surgical resection of the primary tumor could potentially be a more cost-effective intervention compared with novel systemic therapy in the management of metastatic colorectal cancer,” he concluded.

Susan London/Frontline Medical News

In a second study, Dr. Aaron Lewis, a surgical oncology fellow at the City of Hope, Duarte, Calif., and colleagues analyzed data from patients with stage IV colon cancer in the Surveillance, Epidemiology, and End Results (SEER) database for the years 1998 through 2011. They excluded those who died within 30 days of diagnosis or had resection of metastases. Overall, 70% of the 28,068 included patients had resection of their primary.

In multivariate analyses, patients who underwent resection had half the risk of death when compared with peers who did not have this surgery (hazard ratio, 0.49), reported Dr. Lewis.

Findings were essentially the same when the analysis was repeated in a subset of matched patients: Median survival was 17 months with resection versus 9 months without it (hazard ratio, 0.48; P less than .0001). Estimated 3-year survival was 23% and 6%, respectively.

“There are limitations, factors that we couldn’t completely control for. For example, there is no chemotherapy data in the SEER database. We didn’t know the timing of surgery in relation to chemotherapy. And we didn’t know whether these patients were asymptomatic or symptomatic,” Dr. Lewis noted in an interview. “But analysis of this huge group of patients in the United States that are getting treated shows that there is a survival benefit.”

Possible reasons why surgery might prolong life in this setting are unknown but may include the effects of tumor debulking or some enhancement of the immune response, he proposed.

To definitively confirm a survival benefit, a randomized controlled trial is needed, he agreed. “This seems to be a popular question in the literature in the last couple of years, so maybe somebody will be willing to take it on.”

In a third study, a team led by Dr. Zeinab Alawadi, a surgeon and postdoctoral fellow at the University of Texas MD Anderson Cancer Center, Houston, analyzed data from 14,399 patients in the National Cancer Data Base. They had been diagnosed with stage IV colon cancer between 2003 and 2005. The researchers excluded patients who had nonelective resection or surgery at other sites, such as metastasectomy.

The primary tumor was resected in 55% of all patients studied and in 74% of patients included in a 1-year landmark analysis done to account for early deaths related to comorbidity or disease burden, reported Dr. Alawadi.

In the entire cohort, primary resection conferred a significant survival benefit after standard multivariate adjustment (hazard ratio, 0.39) that persisted after propensity score weighting to account for treatment selection bias (hazard ratio, 0.41). The benefit was also significant, but much attenuated, in an instrumental variable analysis, another method for accounting for treatment selection bias (relative mortality rate, 0.88).

In the 1-year landmark population, primary resection conferred a smaller significant survival benefit after standard multivariate adjustment (hazard ratio, 0.60) that persisted after propensity score weighting (hazard ratio, 0.59). But there was no longer a significant benefit in the instrumental variable analysis here.

“Among the entire cohort of patients with stage 4 colon cancer, primary tumor resection offered no survival benefit over systemic chemotherapy alone when the [instrumental variable] method was applied at the 1 year landmark,” the investigators write.

“Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of [primary tumor resection],” they concluded.

SAN FRANCISCO – Resecting the primary tumor in patients with metastatic colon or colorectal cancer may prolong survival. But then again, it may not.

This was the overarching take-home message from a trio of cohort studies presented at the Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. Results were reported in a poster session.

“Whereas surgery is the primary treatment of localized colorectal cancer, resection of the primary tumor in patients with incurable metastatic disease is usually recommended for palliative purposes to manage obstruction, perforation, or bleeding,” Dr. Shahid Ahmed, lead investigator of one of the studies, noted in comments provided by e-mail. “The role of surgical resection of the primary tumor in patients with newly diagnosed incurable stage IV colorectal cancer remains controversial.”

In earlier research, he and colleagues found a survival benefit of primary resection among Canadian patients whose cancer was diagnosed between 1992 and 2005 (Cancer 2014;120:683-91). But the majority did not receive systemic therapy, and those who did were often given older regimens.

In a new study aimed at testing the association in the contemporary treatment era, the researchers analyzed data from 569 patients with stage IV colorectal cancer diagnosed between 2006 and 2010 who had a median follow-up of 11 months. Overall, 55% had resection of the primary tumor.

Among the 57% of patients who received systemic therapy, 91% received FOLFIRI or FOLFOX, 65% received bevacizumab (Avastin), and 10% received cetuximab (Erbitux) or panitumumab (Vectibix), according to Dr. Ahmed, professor of medicine, University of Saskatchewan, Canada.

Results for the entire cohort showed that median overall survival was 18 months in patients who had resection of their primary versus 4 months in those who did not (multivariate hazard ratio, 0.44; P less than .001).

Among the subgroup of patients who received chemotherapy, median survival was 27 months with primary resection versus 14 months without it (P less than .0001). And among the subgroup that specifically received FOLFIRI or FOLFOX and a biologic agent, it was 35 months with primary resection and 23 months without it (P less than .001).

“Surgical resection of primary tumor improves survival of patients with stage IV colorectal cancer, independent of other prognostic variables including age, performance status, comorbid illness, and chemotherapy,” maintained Dr. Ahmed. “The current study validates our findings and supports surgical resection of primary tumor in patients with stage IV colorectal cancer who are treated with modern chemotherapy and biologics.

“A well-designed prospective randomized trial is warranted to confirm the survival benefit conferred by the primary tumor resection,” he added, noting that two such trials in Europe – SYNCHRONOUS and CAIRO4 – are underway.

“If the magnitude of survival benefit is confirmed in these future randomized studies, surgical resection of the primary tumor could potentially be a more cost-effective intervention compared with novel systemic therapy in the management of metastatic colorectal cancer,” he concluded.

Susan London/Frontline Medical News

In a second study, Dr. Aaron Lewis, a surgical oncology fellow at the City of Hope, Duarte, Calif., and colleagues analyzed data from patients with stage IV colon cancer in the Surveillance, Epidemiology, and End Results (SEER) database for the years 1998 through 2011. They excluded those who died within 30 days of diagnosis or had resection of metastases. Overall, 70% of the 28,068 included patients had resection of their primary.

In multivariate analyses, patients who underwent resection had half the risk of death when compared with peers who did not have this surgery (hazard ratio, 0.49), reported Dr. Lewis.

Findings were essentially the same when the analysis was repeated in a subset of matched patients: Median survival was 17 months with resection versus 9 months without it (hazard ratio, 0.48; P less than .0001). Estimated 3-year survival was 23% and 6%, respectively.

“There are limitations, factors that we couldn’t completely control for. For example, there is no chemotherapy data in the SEER database. We didn’t know the timing of surgery in relation to chemotherapy. And we didn’t know whether these patients were asymptomatic or symptomatic,” Dr. Lewis noted in an interview. “But analysis of this huge group of patients in the United States that are getting treated shows that there is a survival benefit.”

Possible reasons why surgery might prolong life in this setting are unknown but may include the effects of tumor debulking or some enhancement of the immune response, he proposed.

To definitively confirm a survival benefit, a randomized controlled trial is needed, he agreed. “This seems to be a popular question in the literature in the last couple of years, so maybe somebody will be willing to take it on.”

In a third study, a team led by Dr. Zeinab Alawadi, a surgeon and postdoctoral fellow at the University of Texas MD Anderson Cancer Center, Houston, analyzed data from 14,399 patients in the National Cancer Data Base. They had been diagnosed with stage IV colon cancer between 2003 and 2005. The researchers excluded patients who had nonelective resection or surgery at other sites, such as metastasectomy.

The primary tumor was resected in 55% of all patients studied and in 74% of patients included in a 1-year landmark analysis done to account for early deaths related to comorbidity or disease burden, reported Dr. Alawadi.

In the entire cohort, primary resection conferred a significant survival benefit after standard multivariate adjustment (hazard ratio, 0.39) that persisted after propensity score weighting to account for treatment selection bias (hazard ratio, 0.41). The benefit was also significant, but much attenuated, in an instrumental variable analysis, another method for accounting for treatment selection bias (relative mortality rate, 0.88).

In the 1-year landmark population, primary resection conferred a smaller significant survival benefit after standard multivariate adjustment (hazard ratio, 0.60) that persisted after propensity score weighting (hazard ratio, 0.59). But there was no longer a significant benefit in the instrumental variable analysis here.

“Among the entire cohort of patients with stage 4 colon cancer, primary tumor resection offered no survival benefit over systemic chemotherapy alone when the [instrumental variable] method was applied at the 1 year landmark,” the investigators write.

“Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of [primary tumor resection],” they concluded.

SAN FRANCISCO – Resecting the primary tumor in patients with metastatic colon or colorectal cancer may prolong survival. But then again, it may not.

This was the overarching take-home message from a trio of cohort studies presented at the Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. Results were reported in a poster session.

“Whereas surgery is the primary treatment of localized colorectal cancer, resection of the primary tumor in patients with incurable metastatic disease is usually recommended for palliative purposes to manage obstruction, perforation, or bleeding,” Dr. Shahid Ahmed, lead investigator of one of the studies, noted in comments provided by e-mail. “The role of surgical resection of the primary tumor in patients with newly diagnosed incurable stage IV colorectal cancer remains controversial.”

In earlier research, he and colleagues found a survival benefit of primary resection among Canadian patients whose cancer was diagnosed between 1992 and 2005 (Cancer 2014;120:683-91). But the majority did not receive systemic therapy, and those who did were often given older regimens.

In a new study aimed at testing the association in the contemporary treatment era, the researchers analyzed data from 569 patients with stage IV colorectal cancer diagnosed between 2006 and 2010 who had a median follow-up of 11 months. Overall, 55% had resection of the primary tumor.

Among the 57% of patients who received systemic therapy, 91% received FOLFIRI or FOLFOX, 65% received bevacizumab (Avastin), and 10% received cetuximab (Erbitux) or panitumumab (Vectibix), according to Dr. Ahmed, professor of medicine, University of Saskatchewan, Canada.

Results for the entire cohort showed that median overall survival was 18 months in patients who had resection of their primary versus 4 months in those who did not (multivariate hazard ratio, 0.44; P less than .001).

Among the subgroup of patients who received chemotherapy, median survival was 27 months with primary resection versus 14 months without it (P less than .0001). And among the subgroup that specifically received FOLFIRI or FOLFOX and a biologic agent, it was 35 months with primary resection and 23 months without it (P less than .001).

“Surgical resection of primary tumor improves survival of patients with stage IV colorectal cancer, independent of other prognostic variables including age, performance status, comorbid illness, and chemotherapy,” maintained Dr. Ahmed. “The current study validates our findings and supports surgical resection of primary tumor in patients with stage IV colorectal cancer who are treated with modern chemotherapy and biologics.

“A well-designed prospective randomized trial is warranted to confirm the survival benefit conferred by the primary tumor resection,” he added, noting that two such trials in Europe – SYNCHRONOUS and CAIRO4 – are underway.

“If the magnitude of survival benefit is confirmed in these future randomized studies, surgical resection of the primary tumor could potentially be a more cost-effective intervention compared with novel systemic therapy in the management of metastatic colorectal cancer,” he concluded.

Susan London/Frontline Medical News

In a second study, Dr. Aaron Lewis, a surgical oncology fellow at the City of Hope, Duarte, Calif., and colleagues analyzed data from patients with stage IV colon cancer in the Surveillance, Epidemiology, and End Results (SEER) database for the years 1998 through 2011. They excluded those who died within 30 days of diagnosis or had resection of metastases. Overall, 70% of the 28,068 included patients had resection of their primary.

In multivariate analyses, patients who underwent resection had half the risk of death when compared with peers who did not have this surgery (hazard ratio, 0.49), reported Dr. Lewis.

Findings were essentially the same when the analysis was repeated in a subset of matched patients: Median survival was 17 months with resection versus 9 months without it (hazard ratio, 0.48; P less than .0001). Estimated 3-year survival was 23% and 6%, respectively.

“There are limitations, factors that we couldn’t completely control for. For example, there is no chemotherapy data in the SEER database. We didn’t know the timing of surgery in relation to chemotherapy. And we didn’t know whether these patients were asymptomatic or symptomatic,” Dr. Lewis noted in an interview. “But analysis of this huge group of patients in the United States that are getting treated shows that there is a survival benefit.”

Possible reasons why surgery might prolong life in this setting are unknown but may include the effects of tumor debulking or some enhancement of the immune response, he proposed.

To definitively confirm a survival benefit, a randomized controlled trial is needed, he agreed. “This seems to be a popular question in the literature in the last couple of years, so maybe somebody will be willing to take it on.”

In a third study, a team led by Dr. Zeinab Alawadi, a surgeon and postdoctoral fellow at the University of Texas MD Anderson Cancer Center, Houston, analyzed data from 14,399 patients in the National Cancer Data Base. They had been diagnosed with stage IV colon cancer between 2003 and 2005. The researchers excluded patients who had nonelective resection or surgery at other sites, such as metastasectomy.

The primary tumor was resected in 55% of all patients studied and in 74% of patients included in a 1-year landmark analysis done to account for early deaths related to comorbidity or disease burden, reported Dr. Alawadi.

In the entire cohort, primary resection conferred a significant survival benefit after standard multivariate adjustment (hazard ratio, 0.39) that persisted after propensity score weighting to account for treatment selection bias (hazard ratio, 0.41). The benefit was also significant, but much attenuated, in an instrumental variable analysis, another method for accounting for treatment selection bias (relative mortality rate, 0.88).

In the 1-year landmark population, primary resection conferred a smaller significant survival benefit after standard multivariate adjustment (hazard ratio, 0.60) that persisted after propensity score weighting (hazard ratio, 0.59). But there was no longer a significant benefit in the instrumental variable analysis here.

“Among the entire cohort of patients with stage 4 colon cancer, primary tumor resection offered no survival benefit over systemic chemotherapy alone when the [instrumental variable] method was applied at the 1 year landmark,” the investigators write.

“Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of [primary tumor resection],” they concluded.