2022 - Preoperative Short-Course Radiotherapy Followed by Chemotherapy and PD-L1 Inhibitor for Locally Advanced Rectal Cancer: A Prospective Phase II Study

Purpose/Objective(s): Locally advanced rectal cancer (LARC) remains a therapeutic challenge due to low sphincter preservation rates, high risks of distant metastasis, and limited survival benefits with conventional neoadjuvant chemoradiotherapy (nCRT). This phase II study evaluated the efficacy and safety of preoperative short-course radiotherapy (SCRT) followed by chemotherapy and the PD-L1 inhibitor (Adebrelimab) in promoting tumor regression in patients with LARC.

Materials/Methods: This prospective, single-arm, single-center trial enrolled patients with stage II/III locally advanced rectal cancer (LARC), irrespective of mismatch repair (MMR) or microsatellite instability (MSI) status. Participants received short-course radiotherapy (SCRT; 5 × 5 Gy) followed by 4 cycles of Adebrelimab (20 mg/kg) combined with CAPOX chemotherapy. After neoadjuvant therapy, patients underwent either total mesorectal excision (TME) surgery or were managed with a watch-and-wait (W&W) strategy. The primary endpoints were pathological complete response (pCR) rate and clinical complete response (cCR) rate or near-cCR for patients without surgical evaluation. Secondary endpoints included toxicity, disease-free survival (DFS), and sphincter preservation rate. Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Results: From 2024-6-1 to 2025-9-12, 58 patients were enrolled. The median age was 57 years (range, 27-75). Most tumors were located in the lower rectum (70.7%, 41/58), were stage IIIB-IIIC (96.5%, 56/58), and were microsatellite stable (MSS, 98.3%, 57/58). All patients completed short-course radiotherapy (SCRT), and 79.3% (46/58) completed four cycles of neoadjuvant immunochemotherapy. Of the 16 patients with a post-treatment efficacy evaluation of partial response (PR) or stable disease (SD) who subsequently underwent total mesorectal excision (TME) surgery, the pathologic complete response (pCR) rate was 31.3% (5/16). Additionally, 32.8% (19/58) of patients achieved a clinical complete response (cCR) or near-cCR and adopted a watch-and-wait (W&W) strategy. Two patients experienced disease progression, one was lost to follow-up, and one withdrew. The overall anal preservation rate was 84.5% (49/58). Treatment-emergent adverse events (TEAEs) of grade 3 or higher occurred in 56.9% (33/58) of patients, most commonly radiation proctitis (25.9%, 15/58), hypokalemia (12.1%, 7/58), and decreased platelet count (10.3%, 6/58). No treatment-related deaths were reported.

Conclusion: SCRT combined with Adebrelimab and chemotherapy demonstrated promising efficacy and manageable toxicity in LARC, supporting further investigation in randomized trials.