3439 - Treatment Outcomes and Prognostic Factors in Young-Onset Rectal Cancer
Presenter(s)
D. Hong1, A. Eltahir2, S. Oluyale2, C. Zivanov2, B. Kalaghchi1, D. Caputa3, N. Kau4, M. Iglesia5, M. R. Waters1, A. Mo1, W. Chapman Jr2, and H. Kim1; 1WashU Medicine, Department of Radiation Oncology, St. Louis, MO, 2WashU Medicine, Department of Surgery, St. Louis, MO, 3Saint Louis University School of Medicine, St. Louis, MO, 4Washington University School of Medicine, St. Louis, MO, 5WashU Medicine, Division of Oncology, St. Louis, MO
Purpose/Objective(s): The incidence of young-onset rectal cancer (YORC, age <50) is increasing in the US. Patients with YORC present with fewer comorbidities and longer life expectancy than later-onset cohorts, thus, toxicity and oncologic outcomes carry greater clinical implications. We evaluated treatment outcomes, prognostic factors, and the impact of clinical, socioeconomic, and treatment variables in YORC patients.
Materials/Methods: A retrospective cohort analysis of 278 YORC patients (2009–2023) at a single tertiary center was performed. Primary endpoints were disease-free (DFS), cancer-specific (CSS), and overall survival (OS). Secondary analyses analyzed survival and late toxicity by treatment paradigms—total neoadjuvant therapy (TNT), short-course radiation therapy (SCRT), long-course chemoradiotherapy (LCCRT), and nonoperative management (NOM)—and socioeconomic factors. Treatment-related comparisons were also propensity score (PS) matched by sex, TNM stage, and tumor distance from the anal verge. Late toxicities (>3 months) were assessed per CTCAE V5.0. Univariate and multivariate Cox models identified survival predictors, with toxicity comparisons via Mann-Whitney U tests.
Results: The cohort was 59% male and 89% white, with a mean age of 42.8 years and a median follow-up of 3.63 years. Most had locally advanced disease (74% T3/T4, 73% node-positive), received TNT (62%), and underwent surgery (86%). Positive surgical margins (HR 4.55, 95% CI 1.96–10.57) and proximity to anal verge (HR 1.11 per cm, starting distance 18 cm, 95% CI 1.02-1.20) were associated with worse DFS. M1 disease was associated with worse CSS (HR 8.28, 95% CI 4.15–16.53) and OS (HR 7.62, 95% CI 3.94–14.75). Gender, T/N stage, and distance from cancer center were not associated with any primary endpoints. Among those who received modern (2015-2023) SCRT (n=116) vs LCCRT (n=23), 3-year DFS (71.2% [LCCRT] vs. 82.3% [SCRT]), CSS (88.7% vs. 91.5%), and OS (88.7% vs. 91.5%), were comparable, which remained similar after 2:1 PS match. Among patients who achieved clinical complete response (CCR) to TNT and elected to pursue NOM (n=37; median follow-up 2.98 years), the 1- and 3-year organ preservation rates were 97% and 63%, respectively; 3-year DFS was 93%. Survival outcomes did not differ from immediate resection after a CCR and remained similar after 2:1 PS match. TNT resulted in high rates of late G2+ neuropathic (26%) and GI (21%) toxicities. Of the G2+ pelvic toxicities reported (3.5%), all were at least partially attributable to RT, including one case of osteoradionecrosis, two atraumatic hip fractures, and four instances of severe pelvic floor dysfunction. Only one late G2 GI toxicity was observed after organ preservation (5%).
Conclusion: SCRT and NOM appear effective in YORC, with NOM demonstrating comparable survival and low GI toxicity. Observed late toxicities raise concerns about long-term survivorship and support future exploration of radiotherapy-based modifications to mitigate pelvic toxicity.