Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer: A Comparison of Short-and Long-Term Oncologic Outcomes

Objective: To evaluate the impact of neoadjuvant multi-Agent systemic chemotherapy and radiation (TNT) vs neoadjuvant single-Agent chemoradiation (nCRT) and multi-Agent adjuvant chemotherapy on overall survival (OS), tumor downstaging, and circumferential resection margin (CRM) status in patients with locally advanced rectal cancer. Summary of Background Data: Outside of clinical trials and small institutional reports, there is a paucity of data regarding the short and long-Term oncologic impact of TNT as compared to nCRT. Methods: Adult patients with stage II-III rectal adenocarcinoma were identified in the National Cancer Database [2006-2015]. Results: Out of 8,548 patients, 36% received TNT and 64% nCRT. In the cohort, 13% had a pCR and 20% a neoadjuvant rectal (NAR) score <8. In multivariable analysis, as compared to nCRT, TNT demonstrated numerically higher pCR rates (P = 0.05) but had similar incidence of positive CRM (P = 0.11). Similar results were observed with NAR scores <8 as the primary endpoint. After adjusting for confounders, OS was comparable between the 2 groups. Additional factors independently associated with lower OS included male gender, uninsured status, low income status, high comorbidity score, poorly differentiated tumors, abdominoperineal resection, and positive surgical margins (all P <0.01). In separate models, both pCR and a NAR score <8 were associated with improved OS. Conclusion: In this national cohort, TNT was not associated with better survival and/or CRM negative status in comparison with nCRT, despite numerically higher downstaging rates. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with rectal cancer.