SAN FRANCISCO – The common practice of resecting asymptomatic primary tumors in patients with unresectable metastases of colorectal cancer does not improve survival but does increase morbidity, and it should therefore be discontinued, according to the phase 3 iPACS trial.
About 80% of patients with stage IV colorectal cancer at diagnosis have metastases that cannot be resected. “For asymptomatic patients, there is no consensus regarding resection of the primary tumor. There have been no randomized controlled trials comparing upfront chemotherapy with primary tumor resection,” said lead investigator Yukihide Kanemitsu, MD, department of colorectal surgery, National Cancer Center Hospital, Tokyo.
He and coinvestigators with the Japan Clinical Oncology Group enrolled in the randomized controlled trial 160 patients with untreated stage IV colorectal cancer who did not have any symptoms from their primary and had up to three unresectable sites of metastases (liver, lungs, distant lymph nodes, and/or peritoneum).
The trial was stopped early for futility, Dr. Kanemitsu reported at the 2020 GI Cancers Symposium. Median overall survival was slightly more than 2 years regardless of whether patients immediately received chemotherapy or underwent primary tumor resection before receiving chemotherapy.
However, 4% of the patients who underwent resection died in the postoperative period from complications. And the resection group had more frequent and more severe chemotherapy-related morbidity, with a higher rate of grade 3 and 4 adverse events (49% vs. 36%).
“Chemotherapy remains the standard therapy for asymptomatic unresectable stage IV colorectal cancer patients,” Dr. Kanemitsu concluded. “Primary tumor resection is not recommended for these patients.”
RCTs should remain the gold standard
“As someone who has built my career on health services research over the last decade working with real-world data, I have become alarmed in recent years at what appears to be a conversation in our community about leaving the randomized controlled trial behind and just using real-world evidence,” said invited discussant Christopher M. Booth, MD, professor, departments of oncology and medicine, Queen’s University, Kingston, Ont., and Canada Research Chair in Population Cancer Care. “Fundamentally, I think this is a really bad idea. The randomized controlled trial should remain the gold standard for efficacy of new cancer therapies.”
The high level of use of primary tumor resection has largely been driven by a meta-analysis that found a dramatic reduction in risk of death with this surgery (Ann Surg Oncol. 2014;21:3900-8), he noted. However, a subsequent retrospective cohort study showed that the apparent benefit disappeared with application of rigorous statistical methods that compensated for biases in the data (Cancer. 2017;123:1124-33).
“I completely support the conclusions presented today,” Dr. Booth asserted, citing the lack of efficacy and greater morbidity and postoperative mortality of primary tumor resection in iPACS, along with the totality of research evidence. “While we can learn a lot from real-world data, it cannot replace randomized controlled trials. In our patients with an asymptomatic primary tumor in the context of incurable colorectal cancer, I believe there is no longer a role for primary tumor resection.”