Primary Tumor Resection Before Starting Systemic Treatment for Colorectal Cancer Decreases Survival

Human colon cancer, CRC
Investigators assessed differences in 60-day mortality between patients receiving systemic treatment alone vs primary tumor resection followed by systemic treatment for CRC.

Primary tumor resection (PTR) prior to systemic treatment among patients with metastatic colorectal cancer (CRC) was associated with reduced survival at 60 days compared with systemic treatment alone. These findings, from a randomized phase 3 trial, were published in JAMA Surgery.

The CAIR04 trial was conducted between 2012 and 2021 at 45 centers in Denmark and the Netherlands ( Identifier: NCT01606098). Patients (N=198) with CRC were randomly assigned in a 1:1 ratio to receive PTR with systemic treatment (n=99) or systemic treatment alone (n=99). Systemic treatment consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab. Patients were assessed for overall and progression-free survival.

Patients in the PTR and systemic cohorts were 36% and 50% women, aged median 64 and 65 years, 63% and 61% had >1 affected organs, and 90% and 85% had liver involvement, respectively.

The median time from randomization to treatment was 17 (IQR, 11-22) days for the surgical group and 7 (IQR, 5-11) days for the systemic treatment recipients. For the surgery recipients, 73% had a laparoscopic approach and 39% had pT4 tumors resected.

At 60 days, there were more deaths among the PTR cohort (11% vs 3%; P =.03). Among the PTR cohort, patients who died differed significantly from survivors in aspartate aminotransferase levels (P <.001), alanine aminotransferase levels (P =.002), and neutrophil count (P =.04). For the systemic treatment recipients, only serum albumin differed (P =.04).

At 60 days, the PTR recipients had a higher hospitalization rate (97% vs 19%) and hospitalization time (median, 6 vs 0 days; P <.001).

Grades 3 or 4 adverse events were numerically lower among the PTR group (23% vs 30%; P =.25). The most common adverse events for the PTR group were infection (6%), pain (4%), and wound infection (3%); adverse events for the systemic treatment group included diarrhea (9%) and pain (8%).

This study was limited by the fact that not all patients received their allocated treatment and there was a gender imbalance between study arms.

The study authors concluded that systemic treatment alone was associated with a lower mortality rate than PTR prior to chemotherapy among patients with CRC. Additional studies are needed to confirm these findings.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


van der Kruijssen DEW, Elias SG, Vink GR, et al. Sixty-day mortality of patients with metastatic colorectal cancer randomized to systemic treatment vs primary tumor resection followed by systemic treatment: the CAIRO4 phase 3 randomized clinical trial. JAMA Surg. Published online October 6, 2021. doi:10.1001/jamasurg.2021.4992