NEW YORK (Reuters Health) – Contrary to previous reports, primary tumor resection prior to chemotherapy did not confer a survival benefit in colorectal cancer patients in a randomized phase 3 study in Japan.
“I was surprised by the findings because we designed the study to test the superiority of primary tumor resection followed by systemic chemotherapy to systemic chemotherapy alone. I was personally hoping for a positive result,” Dr. Yukihide Kanemitsu of the National Cancer Center Hospital in Tokyo told Reuters Health by email.
“In response to the results,” he said, “the Japanese guideline committee seems to have started working on rewriting the standard treatment in the guidelines.”
As reported in the Journal of Clinical Oncology, between 2012-2019, 165 patients from 38 centers in Japan were randomly assigned to chemotherapy alone or primary tumor resection (PTR) plus chemotherapy. The median age was 65 and about 55% were men. All patients had unresectable stage IV asymptomatic CRC and three or fewer unresectable metastatic diseases, mainly in the liver (about 73%) or lungs (about 25%).
In the chemotherapy-alone arm, chemotherapy was started within 14 days of enrollment. In the PTR plus chemotherapy arm, resection of the primary tumor was performed within 21 days of enrollment.
Two interim analyses were planned; however, when the first interim analysis was performed in September 2019, the trial was terminated due to futility.
With a median follow-up of 22 months, median overall survival was 25.9 months with PTR plus chemotherapy and 26.7 with chemotherapy-alone (hazard ratio, 1.10). Three deaths occurred postoperatively in the PTR plus chemotherapy arm.
Dr. Kanemitsu said, “Thirteen percent of patients in the chemotherapy alone group ultimately developed primary tumor-related complications requiring surgical intervention. I would like to know if the background of these patients was different from the population that did not require intervention, and am planning a secondary study on this.”
Surgical oncologist Dr. Anton Bilchik, chief of gastrointestinal research and of medicine at Saint John’s Cancer Institute at Providence Saint John’s Health Center in Santa Monica, California, commented in an email to Reuters Health, “This is the first randomized controlled trial to show no survival benefit to primary colon resection. This is therefore an important trial, but should be tempered with caution. Very few patients were randomized over a seven-year period at 38 different hospitals.”
“Guidelines should therefore not be changed based on this study alone, and the treatment of these patients should be individualized, especially since minimally invasive techniques and enhanced recovery procedures may allow for rapid recovery after surgery and early initiation of chemotherapy,” he said. “In select patients who respond to systemic therapy, metastasectomy may offer a chance for cure.”
“Resection should be considered in patients who are at risk for bleeding or obstruction or in those with bulky tumors who are likely to develop symptoms which may interrupt treatment with systemic chemotherapy,” he added. “These patients are challenging to manage and the sequencing of treatment should be individualized and reviewed at a multidisciplinary tumor board.”
SOURCE: https://bit.ly/2NxNbQw Journal of Clinical Oncology, online February 9, 2021.