What Predicts Complete Response to Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer?

BACKGROUND: Total neoadjuvant therapy in treatment of stage II-III rectal cancer involves administration of either induction or consolidation chemotherapy with chemoradiation before surgery. Total neoadjuvant therapy is associated with increased complete response rate, which is defined as the proportion of patients who either had pathological complete response after surgery or sustained clinical complete response at least for a year under surveillance. OBJECTIVE: To identify the predictors of complete response to total neoadjuvant therapy and compare different diagnostic tools in predicting complete response. DESIGN: Retrospective cohort study. SETTINGS: A single tertiary-care center. PATIENTS: Stage II-III rectal cancer patients who were diagnosed between January 2015 and December 2021. INTERVENTION: Total neoadjuvant therapy. MAIN OUTCOME MEASURES: Complete response rate, predictors of complete response, sensitivity and specificity of sigmoidoscopy and MRI in predicting complete response. RESULTS: One hundred nineteen patients (mean age 56 [±11.3] years, 47 [39.5%] female, 100 [84%] stage III rectal cancer were included. Median tumor size was 5.1 (4-6.5) cm, 63 (52.9%) were low rectal tumors. Twenty-one (17.6%) patients had extramural vascular invasion, 62 (52.1%) had elevated carcinoembryonic antigen at baseline. One hundred eight (90.8%) patients received consolidation chemotherapy. After total neoadjuvant therapy, 88 (73.9%) out of 119 patients underwent surgery, of whom 20 (22.7%) had pathological complete response. Thirty-one (26.1%) patients underwent watch-and-wait, of whom 24 (77.4%) had sustained clinical complete response. Overall complete response rate was 37%. Low rectal tumors (OR 2.6 [95% CI, 1.1-5.9], p = 0.02) and absence of EMVI [OR 5.4 (95% CI, 1.2-25.1), p = 0.01] were predictors of complete response. In predicting complete response, sigmoidoscopy was more sensitive (76.0% vs. 62.5%) and specific (72.5% vs. 69.2%) than MRI. The specificity further increased when 2 techniques were combined (82.5%). LIMITATIONS: Retrospective study. CONCLUSIONS: Complete response rate after total neoadjuvant therapy was 37%. Low rectal tumors and absence of extramural vascular invasion were predictors of complete response. Sigmoidoscopy was better in predicting incomplete response, whereas combination (MRI and sigmoidoscopy) was better in predicting complete response.