Immunotherapy-Induced Complete Response in dMMR Rectal Cancer-A Surgical Dilemma?
Panagiotis Loufopoulos, Konstantinos Perivoliotis, Danai Chatziathanasiou, Maximos Frountzas, Anisha Sukha, Abdullah Alrebdi, Mohammad Mahmoud Rajab Eddama, Christos Kontovounisios, Shengyang Qiu, Paris Tekkis, Shahnawaz Rasheed
Abstract
Open AccessBACKGROUND: Deficient mismatch repair rectal cancer represents approximately 10% of rectal malignancies and demonstrates exceptional responsiveness to immune checkpoint inhibitors, achieving unprecedented complete response rates approaching 100%. This creates a novel clinical dilemma: should patients achieving complete response undergo standard surgical resection or pursue organ preservation through watch-and-wait management? METHODS: We conducted a comprehensive literature review of clinical trials and retrospective studies published through 2025, focusing on response assessment strategies, decision-making frameworks, oncological outcomes, and quality of life assessments. RESULTS: Landmark studies demonstrated remarkable efficacy with dostarlimab achieving 100% clinical complete response, while surgical cohorts achieved 68-92% pathological complete response rates. Response assessment challenges included pseudoprogression and pseudoresidue phenomena that complicated conventional imaging interpretation and required specialised multimodal evaluation protocols. Comparative analyses suggest equivalent oncological outcomes between surgical and non-surgical approaches in complete responders, achieving 100% disease-free survival at 2-3 years across multiple studies. The watch-and-wait approach offered significant advantages by preserving organ integrity and avoiding surgical morbidity, including permanent colostomy (15.4%) and perioperative complications (19.3%). Conversely, surgical management provided distinct benefits through definitive tissue confirmation and anxiety relief from intensive surveillance requirements and potential recurrence concerns. CONCLUSIONS: The surgery versus watch-and-wait dilemma represents a choice between equally effective oncological approaches with different quality of life implications. Evidence supports individualised decision-making weighing functional preservation benefits against patient preferences and institutional capabilities in this evolving therapeutic landscape.