Primary Tumor Resection Before Systemic Treatment Increases Mortality Among Patients With Metastatic Colorectal Cancer

Findings from the phase 3 CAIRO4 trial suggest patients with metastatic colorectal cancer who received primary tumor resection followed by systemic treatment had higher 60-day mortality than those randomized to systemic treatment alone.

“A majority of patients with synchronous metastatic colorectal cancer have few or no symptoms from the primary tumor. Although primary tumor resection is indicated in case of bleeding, obstruction, and perforation, the need for [primary tumor resection] in patients with an asymptomatic primary tumor remains unclear,” explained Dave E. van der Kruijssen, MD, Department of Medical Oncology, University Medical Center Utrecht, the Netherlands and coauthors.

The randomized, phase 3 CAIRO4 trial enrolled patients with histologically confirmed colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms. Patients were randomized to systemic treatment or primary tumor resection followed by systemic treatment with palliative intent. Systemic treatment consisted of fluoropyrimidine-based chemotherapy with bevacizumab.

The study was conducted in general and academic hospitals in Denmark and the Netherlands by the Danish and Dutch Colorectal Cancer Group. The primary objective of the trial was to compare 60-day mortality rates between treatment arms. Identification of risk factors for 60-day mortality was a secondary objective.

A total of 196 patients were included in the intention-to-treat analysis and randomized to systemic treatment alone (n = 99) or surgery plus systemic treatment (n = 97). The 60-day mortality was 3% (95% CI, 1% to 9%) in the systemic treatment group and 11% (95% CI, 6% to 19%) in the surgery group (P = .03). In the per-protocol analysis, 60-day mortality was 2% (95% CI, 1% to 7%) vs 10% (95% CI, 5% to 18%; P = .048), respectively.

Researchers identified factors associated with significantly higher risk for 60-day mortality among patients receiving primary tumor resection, including elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils.

“Caution should be exercised while considering primary tumor resection in patients who have preoperative elevated serum lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophil levels,” concluded Dr van der Kruijssen and colleagues.

Source:

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. 2021 Dec 1;156(12):1093-1101. doi:10.1001/jamasurg.2021.4992.