Perioperative Systemic Therapy vs Surgery Alone in Colorectal Peritoneal Metastases

Key Takeaways

• Investigators observed longer median overall survival with perioperative systemic therapy, but the survival comparison did not reach statistical significance.
• Safety findings included higher major postoperative morbidity after perioperative treatment and substantial grade 3 or worse toxicity among patients who started systemic therapy.
• The investigators concluded that perioperative systemic therapy could not be recommended for all patients with resectable colorectal peritoneal-only metastases.

In the CAIRO6 phase III trial, perioperative systemic therapy did not significantly improve overall survival compared with upfront surgery alone in patients with resectable colorectal peritoneal-only metastases. The randomized comparison evaluated perioperative systemic therapy plus CRS-HIPEC against upfront CRS-HIPEC alone, with median overall survival of 44 months and 39 months, respectively.

The modified intent-to-treat population included 351 patients, with 173 assigned to perioperative systemic therapy and 178 assigned to surgery alone. Patients were randomly assigned from June 2017 to April 2024 across all nine Dutch tertiary centers and one Belgian tertiary center. Perioperative treatment was given with CRS-HIPEC, the comparator was upfront CRS-HIPEC alone, and overall survival in the mITT population was the primary outcome. CAPOX, FOLFOX, or FOLFIRI, with bevacizumab during early neoadjuvant cycles, were used to test whether systemic therapy altered survival.

Median follow-up was 41 months, with an interquartile range of 21 to 62 months. Median overall survival was 44 months in the perioperative group and 39 months in the surgery-alone group. The corresponding 95% confidence intervals were 30 to 54 months and 31 to 46 months, respectively. The hazard ratio for overall survival was 0.85, with a 95% confidence interval of 0.62 to 1.15. The reported P value was .28.

Among 292 patients who underwent macroscopic complete or near-complete CRS-HIPEC, major 90-day postoperative morbidity affected 49 of 138 perioperative patients and 40 of 154 patients in the surgery-alone group, corresponding to 36% and 26%, respectively. Common grade 3 to 4 postoperative events included intra-abdominal abscess, anastomotic leakage, and fascia dehiscence, while 90-day postoperative mortality was about 1% in each group. Grade 3 or worse systemic therapy-related toxicity occurred in 57% of the 161 patients who started systemic therapy, most often hypertension, diarrhea, neutropenia, and thromboembolic events. One systemic therapy-related death was attributed to hyperglycemia, and postoperative deaths were reported in both treatment groups.