Over the last few decades, the standard of care for locally advanced rectal cancer, involving neoadjuvant chemoradiation followed by surgery, is associated with a pathological complete response rate of only 10-20%. Combination therapy with immune checkpoint inhibitors may improve treatment response. This systematic review examines the current evidence regarding neoadjuvant immune checkpoint inhibitors in locally advanced rectal cancer in terms of treatment efficacy, impact on surgical outcomes, and potential adverse events. A literature search was conducted using the Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Library databases from start of database records to October 31, 2024. All studies that reported outcomes in patients with locally advanced rectal cancer who received immune checkpoint inhibitors as part of their neoadjuvant treatment were included for examination. Primary outcome was pathological complete response rate. Secondary outcomes were major pathological response rate, clinical complete response rate, complete response rate, R0 resection rate, and sphincter preservation rate. Safety data were included where available. Potential biomarkers of treatment response were identified. Twelve studies were reviewed. All were prospective phase I/II clinical trials. The overall pathological complete response rate ranged from 25-62.5% (50% for dMMR/MSI-H; 25-62.5% for pMMR/MSS). The clinical complete response rate ranged from 10.9-100% (56-100% for dMMR/MSI-H; 16.4-48% for pMMR/MSS). The complete response rate ranged from 44-75% (75% for dMMR/MSI-H; 44-56.5% for pMMR/MSS). The R0 resection rate ranged from 94-100% and sphincter preservation rate from 59.4-100%. Majority of adverse events were Grades 1 & 2. Our review was limited by a small number of mostly single-arm studies with lack of long-term survival outcomes, as well as marked clinical and methodological heterogeneity among included studies. Combination therapy with immune checkpoint inhibitors in locally advanced rectal cancer appears to improve treatment response but high-level evidence and long-term data are still lacking.
Mui et al. (2025) studied this question.