A retropective analysis of colorectal cancer in adolescents and young adults: A report from the Surgical Committee of the Children's Oncology Group

Abstract

9568 Background: The genetic origin, clinical features, and prognosis of early onset colorectal carcinomas (CRC diagnosed ≤ 30 years of age) are poorly understood. To evaluate these parameters, we performed a multi-institutional review. Methods: This is a retrospective review accomplished through a survey of Children's Oncology Group Institutions. 167 patients (median age=21yrs., range 10–30 yrs.) with adequate material were reviewed. Immunostaining for mismatch repair (MMR) proteins (MSH2, MLH1, MSH6, PMS1) was performed for 119 cases with sufficient archival tumor. Survival estimates were computed using Kaplan Meier methodology and associations assessed using a log-rank test or Cox proportional hazards. Results: The overall stage of disease at presentation: 9% stage I, 16% stage II, 34% stage III, 38% stage IV, and 4% unknown. Site of origin in the colon included: 17% right, 8% transverse, 14% left, 15% sigmoid, 37% rectosigmoid or rectum, and 9% unknown. 37% of cancers were poorly differentiated and 23% had signet ring cell features. A family history of CRC was reported in 46 (40%) of 114 patients for whom data were available. HNPCC criteria (Amsterdam II) were met in only 10 of these cases. MMR protein expression was deficient in 20 of 119 evaluable cases (17%) and was correlated to HNPCC status (P<0.0001) but not to other clinical features. R0 resection was accomplished in 115 patients. Of 159 patients with follow-up data the median survival was 44 mos. (95% CI: 31–65mos.). The 1, 3, and 5-year overall survival were 81%, 54%, and 42% respectively. Variables associated with overall survival in univariate analysis included: age (p=0.02), family history of CRC (P=0.03), HNPCC status (P=0.03), stage (P<0.0001), grade (P=0.0003), and R0 status (P<0.0001). Conclusions: CRC in this age group is associated with clinical features distinct from adult CRC, including advanced stage, high grade pathology, and poor survival. The majority of cases occur sporadically, and less than 25% can be associated with HNPCC either by clinical criteria or by MMR immunostaining. Future studies should pursue more detailed molecular characterization, improved detection strategies, and better treatment to improve outcome for these aggressive cancers. No significant financial relationships to disclose.