Cut to chemo.

Top Line: Does primary tumor resection (PTR) improve survival in patients with metastatic colorectal cancer?

The Study: Surgery can play an important role in the management of the primary tumor and metastatic sites for patients with metastatic colorectal cancer. However, there are various metastatic scenarios and it is unclear if surgery is beneficial for each. One scenario is when patients have a resectable primary but unresectable synchronous metastases. In other words, all their disease can’t be resected and they otherwise don’t have a pressing need for surgical symptom relief. In the iPACS trial, patients with primary colorectal adenocarcinoma and 1-3 sites of unresectable metastatic disease (mostly liver metastases) were randomized to standard chemotherapy with or without resection of the primary tumor. Importantly, primary tumor resection was done upfront--not after initial systemic therapy. Patients were required to be asymptomatic from their primary (i.e. no obstructive symptoms). Chemo consisted of mFOLFOX6 or CapeOX, both with bevacizumab. The trial was stopped early for futility after 156 patients were enrolled, and there was no difference in median OS between chemo only (26.7 months) and chemo plus PTR (25.9 months). There was also no difference in median progression-free survival. PTR resulted in higher post-op complications, increased non-hematologic chemo complications, and it also delayed the start of chemo a median of 34 days. Over the follow-up period, 13% of patients in the chemo-only arm required surgery due to the development of symptomatic primary disease.

TBL: For patients with colorectal cancer and unresectable, synchronous metastases, up-front primary tumor resection appears to increase complications without improving survival outcomes. | Kanemitsu, J Clin Oncol 2021