Multicenter cohort study of observation versus maintenance immunotherapy after PD-1-induced clinical complete response in dMMR/MSI-H CRC managed non-operatively

A cohort study at five centers in China investigated whether maintenance immunotherapy is necessary after clinical complete response (cCR) to PD-1 inhibition in dMMR/MSI-H CRC managed non-operatively. All patients underwent endoscopy and site-appropriate cross-sectional imaging to confirm cCR; 62.0% also underwent biopsy. Patients were categorized into observation and maintenance groups according to whether they received maintenance immunotherapy after cCR, defined as at least to addition treatment cycles. The primary endpoint was disease-free survival (DFS) from cCR. Among 129 patients with cCR entering non-operative management, 66 underwent observation and 63 received maintenance immunotherapy. The analytic cohort included 58 patient with a single rectal primary, 61 with a single colon primary, and 10 with synchronous colorectal primaries; 115 (89.1%) had stage I-III disease. Median follow-up from cCR was 32.2 months (IQR 20-4-44.4). Two locoregional regrowths occurred in the observation group within 2 years after cCR; both patients underwent salvage treatment and remained alive. No distant metastases occurred, and the only death was due to COVID-19 without recurrence. Three-year DFS rate was 96.2% with observation and 98.3% with maintenance (p=0.508); corresponding overall survival was 100% and 98.3% (p=0.321). Across the entire treatment and follow-up, any treatment-related adverse event (TRAE) was numerically more frequent in the maintenance group than in the observation group (65.1% versus 59.1%); 15.9% of patients in the maintenance group experienced grade ≥2 TRAEs during maintenance therapy. The authors conclude that these findings suggest that discontinuation after cCR may be reasonable within a watch-and-wait strategy for rectal cancer and provide preliminary support for non-operative management of colon cancer. Prospective validation is warranted.