Rectal Cancer: Clinical and Molecular Predictors of a Complete Response to Total Neoadjuvant Therapy.
Background: Total neoadjuvant therapy in rectal cancer may increase pathological complete response rates potentially allowing for a nonoperative approach.
Objective: The objective was to identify patient and tumor characteristics that predict a complete response following total neoadjuvant therapy.
Methods: This was a retrospective cohort study. Methods: This study was conducted at a university-based National Cancer Institute-designated Comprehensive Cancer Center. Methods: The patients include those with Stage 2 or 3 rectal adenocarcinoma. Methods: Total neoadjuvant therapy, total mesorectal excision, nonoperative management. Methods: Complete response was defined as patients with a clinical complete response undergoing non-operative management who remained cancer-free or patients undergoing surgery with a pathological complete response.
Results: Among 102 patients, median age was 54 years, 69% were male, median carcinoembryonic antigen level was 3.0 ng/mL, and the median distance of the tumor above the anorectal ring was 3 cm. 38 (37%) patients had a complete response which included 15 of 18 (83%) non-operative patients who remained cancer free at a median of 22 months (range 7-48 months) and 23 of 84 (27%) patients who underwent surgery and had a pathologic complete response. The incomplete response group consisted of 61 patients who underwent initial surgery and 3 non-operative patients with regrowth. There were no differences in gender, T-stage or tumor location between groups. Younger age (median 49 vs 55), normal carcinoembryonic antigen (71% vs 41%), clinical node-negative (24% vs 9%), smaller tumors (median 3.9 vs. 5.4 cm), and wild-type p53 (79% vs 47%) and SMAD4 (100% vs 81%) were more likely to have a complete response (all p < 0.05).
Conclusions: This was a retrospective study and small sample size. Conclusions: In patients with rectal cancer treated with total neoadjuvant therapy, more than one-third will achieve a pathological complete response or sustained clinical complete response with non-operative management making oncological resection superfluous in these patients. Smaller, wild-type p53 and SMAD4, and clinically node-negative cancers are predictive features of a complete response. http://links.lww.com/DCR/B889.