Neoadjuvant Immunotherapy for Patients with Microsatellite Instability-High or Pole-Mutated Locally Advanced Colorectal Cancer with Bulky Tumors: New Optimization Strategy

BackgroundICIs have a significant therapeutic effect in patients with MSI-H early-stage and mCRC. However, data are rare on neoadjuvant immunotherapy for patients with MSI-H or POLE-mutated LACRC with bulky tumors (>8 cm).ObjectiveTo evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with MSI-H or POLE-mutated LACRC with bulky tumors.DesignThis was a retrospective observational study.PatientsWe retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy. All these patients had bulky tumor scheduled for multivisceral resection, or potentially local resectable metastatic lesions, or could not undergo initial R0 resection.Main Outcome MeasuresPathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan–Meier method.ResultsThe incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1–8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred, and the most common complication was Grade I/II chylous leakage in 3 patients after radical right hemicolectomy. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%.ConclusionsPreoperative ICI therapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR.