Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait

Background: The watch-and-wait strategy provides an opportunity to pursue non-operative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near complete response remains controversial. Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy. Design: Retrospective cohort study. Settings: Comprehensive cancer center in New York. Patients: Patients with rectal adenocarcinoma diagnosed between January 2006 to December 2020. Interventions: A watch-and-wait strategy of active surveillance was offered to patients if they achieved clinical complete response. Salvage surgery was utilized for watch-and-wait patients with local regrowth. Patients with an incomplete response underwent total mesorectal excision Main Outcome Measures: Local regrowth rate, organ preservation rate, disease-free survival and overall survival. Results: Patients with rectal adenocarcinoma (n = 1230) were divided into 3 response cohorts—incomplete (n = 646), near-complete (n = 189) and complete (n = 395). Eighty-one (43%) patients in the near-complete group and 351 (89%) patients in the complete group entered watch-and-wait. Three-year local regrowth rates were 40% and 24% in the near-complete and complete response cohorts, respectively. The 5-year organ preservation rate was 53% in near-complete responders, and 73% in complete responders. Five-year disease-free survival increased with greater clinical response to neoadjuvant therapy with intermediate outcomes noted for patients with a near-complete (73%) compared to complete (82%) or incomplete response (68%). Overall survival at 5 years was similar between the three cohorts (complete 90%, near-complete 86%, and incomplete 85%). Limitations: Retrospective nature. Conclusion: Greater clinical response to neoadjuvant therapy is associated with improved oncologic outcomes. Near-complete responders may avoid surgery and still achieve high organ preservation rates yet experience greater local regrowth rates than clinical complete response patients. Ongoing prospective trials integrating watch-and-wait after complete response as determined by uniform criteria will bolster the work to help treating physicians better select patients who qualify for active surveillance. See Video Abstract .