Total neoadjuvant therapy with short course radiation compared to concurrent chemoradiation in rectal cancer.

Abstract

486 Background: Total Neoadjuvant Therapy (TNT), or delivery of all radiation and chemotherapy prior to surgery, has improved complete response and downstaging rates compared to adjuvant therapy in patients with rectal cancer. Data regarding the use of short course radiation in the setting of TNT (SC-TNT) are limited. This study compares the pathologic complete response rate (pCR), Neoadjuvant Rectal (NAR) Score – a validated predictor of outcome based on tumor downstaging, and recurrence rates for patients receiving SC-TNT versus chemoradiation (CRT). Methods: Patients who underwent neoadjuvant therapy followed by total mesorectal excision for Stage II or III rectal cancer from 2009 to 2018 were included in this retrospective cohort study. CRT recipients (50-55Gy/25-28 fx with concurrent 5-FU or capecitabine) comprised one cohort; the other included SC-TNT recipients (25-35Gy/5 fx followed by CAPOX or FOLFOX chemotherapy). The primary outcome of pCR rate was assessed in univariate analysis; the secondary outcome of NAR score was calculated and categorized as “Low” ( < 8), “Intermediate” (8–16), and “High” ( > 16). Finally, recurrence rates were measured and classified as local, distant, or both. Results: Of 388 eligible patients, 236 (60.8%) were treated with CRT and 152 (39.2%) underwent SC-TNT. On univariate analysis, the SC-TNT cohort had more advanced disease (77% Stage III disease vs. 67%, p = 0.04) and longer elapsed time between radiation completion and surgery (Median 131 vs. 63 days; p < 0.01). SC-TNT achieved a numerically higher pCR rate compared to CRT (25.0% vs. 19.1%, p = 0.16). Odds of achieving a “low” NAR Score trended higher among the SC-TNT cohort (OR 1.49, 95% CI 0.96 – 2.31). Recurrence rates were also similar (14.3% vs. 14.9%, p = 0.87) over comparable follow-up (CRT = 30.5 months [IQR 11.1 – 49.0]; SC-TNT = 22.3 months [IQR 10.8 – 61.0]; p = 0.82). Conclusions: SC-TNT yielded a pCR rate of 25% and overall recurrence rate of 14.9% among patients with locally advanced rectal cancer. Short course radiation with neoadjuvant multiagent chemotherapy is at least as effective as long-course CRT. [Table: see text]