Abstract C026: Disparate response to chemoradiation in early onset vs late onset rectal cancer

Purpose: The study aimed to evaluate the response to neoadjuvant chemoradiation (CRT) in early onset (EO) rectal cancer (RC) patients in a large national dataset. Methods: The National Cancer Database (NCDB) is a large hospital-based oncology registry that captures case-level data on approximately 70% of newly diagnosed cancers in the United States. A cohort of locally advanced RC patients, stage II-III, who were treated with CRT prior to surgical resection was identified using the 2022 participant user file, covering 2004-2022. The cohort was divided into EO (<40 years of age) RC and later onset (LO) RC. Downstaging was defined as decreased stage from initial clinical to final pathologic staging. Continuous variables were compared using Wilcoxon rank sum tests and categorical variables were compared using Chi-square and Fisher’s Exact Tests. Logistic regression models were used to assess the associations of pathologic complete response (pCR) and downstaging with reference to age as a 6-level categorical variable (18-39, 40-49, 50-59, 60-69, 70-79, 80+) while adjusting for possible confounders including stage, Charlson-Deyo Comorbidity Classification (CDCC), sex, race, ethnicity, year of diagnosis, insurance status and income. All analysis was conducted in SAS 9.4 and R 4.4.2. Results: 37,508 patients were identified, including 1,722 EORC patients. EO patients were more commonly female, Black, Asian or Hispanic (p<0.001). EO patients also had lower CDCC scores (e.g. 93% vs 77% CDCC 0; p<0.001) and higher-grade tumors (e.g. 12% vs 9.2% poorly differentiated; p<0.001). Examining clinical staging, EO patients exhibited slightly increased frequency of T2 staging [6.6% vs 4.9%] and decreased T3 staging [81.5% vs 83.7%] (p=0.007) with more advanced lymph node (LN) staging [N1:49.4% vs 44.4%; N2:23.3% vs 13.2%] (p<0.001). On univariate analysis, EO patients had higher numbers of examined LNs (median 17 vs 14; p<0.001) and positive LNs (mean 1.60 vs 0.93, p<0.001). While the rate of pathologic complete response did not differ by age, EO patients had less downstaging of the primary tumor (47.6% vs 50.9%, p=0.007). EO also had more N downstaging and N upstaging (Downstaging: 46.3% vs 39.8%; Upstaging: 15.4% vs 12.6%, p<0.001). On adjusted analysis, probability of pCR was greatest at age 70-79 (OR 1.24, p=0.03). All age groups 50 and above were associated with increased LN downstaging (ORs 1.20-1.42; p values <0.01). Also, higher T stage correlated with greater odds of LN downstaging (e.g. cT4 OR 2.24, p<0.001). Odds of primary T downstaging increased for ages 60-69 (OR 1.13, p=0.014) and 70-79 (OR 1.20, p=0.001). Also, these odds decreased with greater N stage (N1: OR 0.73, p<0.001; N2: OR 0.68, p<0.001). Conclusions: EORC patients presented with higher grade tumors and more aggressive LN staging than LORC. Generally, pathological response after CRT was stronger with increased age, including pCR, LN and primary T downstaging. Additional analysis is needed to understand the differing rates of clinical LN involvement and downstaging in EO patients. Citation Format: Joshua E. Meyer, Jordan Fredette, Christopher G. Cann. Disparate response to chemoradiation in early onset vs late onset rectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr C026.