eP210 - Delayed Surgery After Neoadjuvant Short-course Radiation for Rectal Cancer Improves Pathologic Outcomes Without Impacting Survival: A National Cancer Database Analysis

Purpose/Background: Short course radiotherapy (SCRT), or the 5x5 protocol which delivers 5 grays (Gy) of radiation over five days for a total of 25 Gy, is an acceptable alternative to standard neoadjuvant chemoradiation for rectal cancer. The optimal interval from completion of SCRT to surgery has not been determined. The purpose of this study was to investigate the pathologic outcomes and overall survival with variable radiation to surgery time interval (RTSI) following SCRT.Methods/Interventions: The National Cancer Database was queried for adults with rectal cancer diagnosed from 2005 to 2020 who received curative intent neoadjuvant SCRT followed by surgical resection. Patients were grouped by whether they also received neoadjuvant chemotherapy. Outcomes were analyzed for RTSI at three timepoints, which were defined as within 1 week (early), 1 to 4 weeks (intermediate), and over 4 weeks (delayed). We analyzed the primary outcomes of surgical margins and tumor downstaging effect, defined as the reduction from clinical to pathologic T stage. In addition we evaluated the outcomes of pathologic characteristics, perioperative outcomes, and overall survival.Results/Outcomes: The total cohort consisted of 1154 patients (mean age 59.5 ± 13.2, 57.9% male), of whom 671 (58.2%) patients received neoadjuvant SCRT along with induction or consolidation chemotherapy (Group 1), and 483 patients (41.9%) received neoadjuvant SCRT only (Group 2). In Group 2, 232 patients (48.0%) received adjuvant chemotherapy. In Group 1, median RTSI was 29 days and 50.2% of patients had a delayed interval to surgery. In Group 2, median RTSI was 9 days and 27.3% of patients had a delayed interval to surgery. Adjusting for age, sex, race, clinical T stage, and tumor grade, RTSI did not affect circumferential margin positivity or presence of a downstaging effect in either group. However, the extent of tumor downstaging was significantly greater with delayed vs. early interval to surgery in Group 1 (χ2(2)=14.4, p=0.0007) and in Group 2 (χ2(2)=8.3, p=0.016), based on the Kruskal-Wallis test with pairwise comparison. Delayed interval to surgery decreased the likelihood of lymphovascular invasion in Group 1 (OR 0.53; 95% CI, 0.33-0.85; p=0.009) and decreased the likelihood of tumor deposits in both Group 1 (OR 0.46; 95% CI, 0.30-0.71; p < 0.001) and Group 2 (OR 0.37; 95% CI 0.21-0.65; p=0.001). Delayed surgery also increased the likelihood of a compete pathologic response in Group 1 (OR 2.86; 95% CI, 1.06-7.76; p=0.039). Other outcomes including perineural invasion, length of stay, 30-day and 90-day mortality, and unplanned readmission were not impacted by RTSI. Adjusting for demographics, tumor grade, staging, and adjuvant chemotherapy, overall survival was not impacted by RTSI in either group.Conclusion/

Discussion: Delaying surgery by at least 4 weeks following neoadjuvant short course radiation for rectal cancer results in favorable pathologic outcomes and does not affect overall survival, regardless of administration of neoadjuvant chemotherapy. A delay to surgery after SCRT permits time for sufficient preoperative optimization and tumor regression, without a negative impact on readmission, length of stay, or mortality outcomes.