Impact of total neoadjuvant therapy (TNT) on overall complete response (CR) for locally advanced rectal cancer (LARC): A Brazilian real-world study.

54 Background: There are limited data on the impact of TNT on complete response (CR) rates for LARC treated in community settings. Methods: A retrospective cohort study was conducted at two health centers, from January 2019 to August 2023. All consecutive patients with LARC staged cT3-cT4 and/or lymph node- positive (AJCC 8th Edition) who received at least one application of neoadjuvant therapy (NAT)—radiotherapy and/or chemotherapy—were included. The primary outcome was the overall CR rate, stratified by NAT: TNT versus Non-TNT. CR was defined as cases achieving pathological complete response (ypCR) or sustained complete clinical response (cCR) after 12 months for patients undergoing a watchful waiting protocol. Secondary endpoints were ypCR rates and clinical/ hematological toxicities (CTCAE version 5.0) stratified by NAT. Results: Overall, 137 patients were included, with 60 (43.8%) receiving TNT and 77 (56.2%) receiving Non- TNT. The median age was 58.9 years standard deviation (SD): ±11.2 for the TNT group and 59.0 years (SD: ±11.0) for the Non-TNT group. Initial staging for the TNT and Non-TNT groups was as follows: cT3 (61.6% and 67.5%), cT4 (18.3% and 16.8%), and positive lymph nodes (68.3% and 66.2%), respectively. The median distance from the anal verge was 5.5 cm Interquartile range (IQR): 5–9.5 for TNT and 6.0 cm (IQR: 5–10) for Non-TNT. The overall CR rates for the TNT and Non-TNT groups were 28.3% (17/60) and 11.6% (9/77), respectively Odds ratio (OR) = 2.98; 95% CI: 1.24–7.17. The ypCR rates were 20.0% (12/60) for TNT and 7.8% (6/77) for Non- TNT (OR = 2.96; 95% CI: 1.07–8.14). Grade ≥3 clinical toxicities during NAT occurred in 5.0% (3/60) of the TNT group and 6.4% (5/77) of the Non-TNT group (OR = 0.76; 95% CI: 0.19–3.01). Grade ≥3 hematological toxicities during NAT occurred in 3.3% (2/60) of the TNT group and 5.2% (4/77) of the Non-TNT group (OR = 0.62; 95% CI: 0.11–3.49). Conclusions: The data suggest a higher CR rate in the TNT group compared to the Non-TNT group among patients with LARC treated in community settings.