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 nonoperative 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 and December 2020. INTERVENTIONS: A watch-and-wait strategy of active surveillance was offered to patients if they achieved clinical complete response. Salvage surgery was used 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 patients (43%) in the near-complete group and 351 patients (89%) 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 (68%) response. Overall survival at 5 years was similar between the 3 cohorts (complete 90%, near-complete 86%, and incomplete 85%). LIMITATIONS: Retrospective nature. CONCLUSIONS: 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.