Comparative effectiveness of total neoadjuvant therapy versus standard adjuvant chemotherapy for locally advanced rectal cancer

Abstract Introduction The use of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has been increasing in recent years, but the long-term overall survival characteristics of this approach is currently unknown. Methods We performed a retrospective study of patients with clinical stage II/III rectal cancer within the National Cancer Database. Patients who received TNT (defined as chemotherapy, followed by CRT, followed by surgery) were propensity score matched to patients who received adjuvant therapy (defined as CRT, followed by surgery, followed by chemotherapy). We compared overall survival (OS) and rates of pathologic complete response (pCR) between the two arms. Results Of the 4,300 patients in our cohort, 3,502 (81%) received adjuvant therapy and 798 (19%) received TNT. At baseline, patients who received TNT were more likely to have higher clinical T and N stages (p Conclusion In this observational study, we found TNT was not associated with a lower OS compared to standard adjuvant chemotherapy. This finding potentially reassures clinicians choosing TNT as an alternative to adjuvant chemotherapy. However, future prospective data are needed to confirm these findings. Microabstract The long-term overall survival characteristics of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has not been well-defined despite its increasing popularity. In a large National Cancer Database cohort, we found that TNT was not associated with worse survival compared to historical controls.