Characterizing patient outcomes and tumor genetics in perinatal early-onset colorectal cancer patients.

Abstract

e15738 Background: The overall incidence of colorectal cancer (CRC) in the United States is declining, however, the incidence of early onset CRC (EOCRC, < age 50) has increased in the past decade. Hereditary cancer syndromes only explain a small proportion of EOCRC cases and ongoing research is investigating the epidemiologic characteristics of EOCRC compared to classical onset ( > age 50) CRC. The University of California San Diego has observed an increase in the number of EOCRC cases in the perinatal period (1 year before and after delivery) across the last 8 years, warranting further investigation into its unique molecular and genetic characteristics during pregnancy and its influence on patient treatment. Methods: We conducted a single-institution retrospective cohort study of EOCRC patients diagnosed in the perinatal period and age-matched controls. Endpoints include patient demographics, systemic therapy plans, molecular and genetic characteristics, and survival outcomes. Patient identification for inclusion and data collection is ongoing. Results: A total of 35 EOCRC patients were identified between 1/1/2018 and 3/1/2025; 9 (25.7%) were diagnosed during or within a year of pregnancy. The average age at diagnosis was 35.6 years old for cases and 37.3 years old for controls (p = 0.26). Since April 2021, across a 54-month period, a total of 4 patients were deceased, with an average survival of 22.8 months for cases vs 24.56 months for control (ns). One case (11.1%) presented with metastatic disease compared to 4 controls (15.4%). Of the 9 EOCRC perinatal patients, 7 received systemic therapy; 2 (22%) received treatment prior to delivery (both receiving a 5-Fluorouracil backbone), in one case (11%) systemic treatment was delayed until after delivery, and in 4 cases (44%) diagnosis was made after delivery (average 8.9 months after). Germline testing was done in 32 (91.4%) of patients. Two cases (22%) had germline mutations, in MLH1 and MSH2. Three controls (11%) had germline mutations, including BRCA1, APC, and MUTYH. The most identified somatic gene mutations were APC with 29 total mutations, 66% vs 46% patients contained at least 1 mutation in APC (10 mutations total in the perinatal group vs. 19 in controls), followed by KRAS with 17 total, 44% vs 50% (4 vs 13), TP53 with 15 total, 33% vs 46% (3 vs 12), SMAD4 with 6 total, 11% vs 19% (1 vs 5), ARID1A with 6 total, 44% vs 8% (4 vs 2), PIK3CA with 5 total, 22% vs 12% (2 vs 3), and PTEN with 3 total, 0% vs 12% (0 vs 3). Conclusions: The overwhelming majority of EOCRC patients undergo germline hereditary cancer screening. Nearly half of our perinatal cohort were diagnosed with CRC after delivery, indicating that there may be a delay in recognizing symptoms of CRC during pregnancy. In this small EOCRC cohort, some tumor mutations among perinatal cases appear over-represented (ARID1A) while others were under-represented (KRAS and TP53). Further data collection and reanalysis are ongoing.