Perioperative systemic therapy provides no significant overall survival benefit for patients with resectable peritoneal-only metastases of colorectal adenocarcinoma compared to surgery alone, according to the phase III CAIRO6 trial published in The Lancet Oncology. Researchers found a median overall survival of 44 months with systemic therapy versus 39 months with surgery alone, a difference that did not reach statistical significance.
Clinical Outcomes in the CAIRO6 Trial
The CAIRO6 trial, conducted across nine Dutch tertiary centers and one Belgian center, randomized 351 patients between June 2017 and April 2024. Patients were assigned to either perioperative systemic therapy combined with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) or upfront CRS-HIPEC alone.
After a median follow-up of 41 months, the hazard ratio for overall survival was 0.85 (95% confidence interval = 0.62–1.15, P = .28). Investigators concluded that because the therapy failed to demonstrate a survival advantage, it cannot be recommended as a standard approach for all patients with this specific diagnosis.
Did you know?
The study utilized multiple systemic therapy regimens, including CAPOX, FOLFOX, or FOLFIRI, with bevacizumab added to specific neoadjuvant cycles at the investigator’s discretion.
Assessing Postoperative Morbidity and Toxicity
The addition of systemic therapy was associated with higher rates of major postoperative morbidity. Among 292 patients who underwent macroscopic complete or near-complete CRS-HIPEC, major 90-day postoperative complications occurred in 36% of the systemic therapy group, compared to 26% in the surgery-alone group.
Common Clavien-Dindo grade 3 to 4 complications included intra-abdominal abscesses, anastomotic leakage, and fascia dehiscence. Systemic therapy itself also carried significant risks. According to the study, 57% of the 161 patients who started systemic therapy experienced grade 3 or worse treatment-related toxicity, with hypertension, diarrhea, neutropenia, and thromboembolic events being the most frequent adverse outcomes.
Postoperative Mortality Rates
Postoperative mortality within 90 days remained low in both study arms. Two patients (1%) in the perioperative systemic therapy group died due to anastomotic leakage and a cerebrovascular accident. One patient (1%) in the surgery-alone group died following anastomotic leakage. Additionally, one patient in the systemic therapy group died from hyperglycemia related to the treatment.
Refining Treatment Paradigms
Researchers Koen P. Rovers and Ignace H. J.
For more updates on oncology research and clinical trial outcomes, subscribe to our newsletter or explore our cancer research archive.
Related reading
