Applicability of cCR assessment criteria in pmmr rectal cancer patients treated with neoadjuvant chemoradiotherapy combined with immunotherapy

This study aimed to assess whether clinical complete response (cCR) criteria developed for neoadjuvant chemoradiotherapy (NACRT) are applicable to patients with proficient mismatch repair locally advanced rectal cancer (LARC) who are treated with NACRT combined with immunotherapy (NAICRT). This retrospective study included 49 LARC patients who received NAICRT and 128 who received NACRT. Clinical response was assessed using two established criteria: the Memorial Sloan Kettering Cancer Center (MSKCC) criteria and the Chinese Watch-and-Wait Database (CWWD) criteria. These criteria integrate findings from digital rectal examination, endoscopy, MRI, and, optionally, carcinoembryonic antigen levels and biopsy results. Pathological complete response (pCR), determined from surgical specimens, was used as the reference standard. The diagnostic performance of these criteria in predicting pCR was evaluated using sensitivity, specificity, accuracy, and area under the curve (AUC). Among the 177 patients, 54 achieved pCR (18 in the NAICRT group and 36 in the NACRT group). MSKCC and CWWD criteria showed comparable performance in the NACRT and NAICRT groups, respectively. Sensitivities were 0.11 and 0.28; specificities, 0.99 and 1.00; accuracies, 0.74 and 0.73; and AUCs, 0.55 and 0.64, with no significant differences between groups. Endoscopy demonstrated sensitivities of 0.28 and 0.61, specificities of 0.96 and 0.90, accuracies of 0.77 and 0.80, and AUCs of 0.67 and 0.76 in the NACRT and NAICRT groups, respectively, with a significant difference in sensitivity (P = 0.02). MRI showed sensitivities of 0.50 and 0.39, specificities of 0.91 and 0.90, accuracies of 0.80 and 0.71, and AUCs of 0.71 and 0.65, without significant differences. The cCR assessment criteria originally developed for NACRT are also applicable to NAICRT patients, showing excellent specificity but suboptimal sensitivity, which may lead to overtreatment of patients with actual pCR. Future studies should focus on enhancing sensitivity to better support organ preservation.