Adjuvant chemotherapy outcomes among patients with stage II early-onset colon cancer in Alberta.

Abstract

e15629 Background: Incidence rates of early-onset colorectal cancer (eoCRC) among adults under the age of 50 years are increasing in Canada and the United States. Despite increasing incidence, eoCRCs represent a minority of CRC diagnoses (~10%) and are underrepresented in randomized trials of novel chemotherapies and targeted agents. As such, robust evidence that can be used to inform the clinical management of eoCRC is lacking. In particular, the appropriateness of adjuvant chemotherapy for individuals with stage II colon cancer is controversial. Given this uncertainty, there is an urgent need for data to clarify whether these practices are helpful or harmful. Objective: This project leveraged existing real-world data to investigate treatment outcomes among eoCRC patients in Alberta and identify areas amenable to intervention. The specific aim was to assess the real-world effectiveness of initiating adjuvant chemotherapy vs. observation on survival in eoCRC. Methods: We conducted a population-based, retrospective cohort study including all patients aged 18to 49 years in Alberta diagnosed with invasive colon cancer from 2004 to 2020. Data from electronic medical records, administrative data claims, and vital statistics were linked. Observational data were used to emulate a target trial comparing the initiation of any adjuvant chemotherapy (fluorouracil/capecitabine-based regimens) vs. observation (no chemotherapy) within 12 weeks of diagnosis. The outcomes were recurrence-free and overall survival. Follow-up began at time of surgery and patients were followed until recurrence, death, last known date of contact with the healthcare system, or administrative end of follow-up (April 2022), whichever occurred first. To address time-varying selection bias, marginal Cox models with artificial cloning and inverse-probability censoring weights were employed to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Results: A total of 230 patients were included, where 94 (41%) initiated chemotherapy and 136 (59%) did not. Patients initiating chemotherapy were more likely to have T4 tumours (42.6% vs. 8.1%), high grade tumours (20.3% vs. 11%) and fewer than 12 examined lymph nodes (8.5% vs. 2.9%). The median time-to-chemotherapy initiation since surgery was 55 days [IQR:38-72]. The risks of recurrence and death were 21% (HR:0.79; 95%CI:0.41-1.51) and 20% (HR:0.80; 95%CI:0.40-1.61) lower among those who initiated chemotherapy versus observation, respectively, but statistical significance was not achieved. Conclusions: Our study did not demonstrate significant survival benefits of initiating adjuvant chemotherapy in stage II early-onset colon cancer. However, we were limited in sample size, outcome events, and data on microsatellite instability. Future studies should explore prediction of high-risk status to identify patients more likely to benefit from adjuvant chemotherapy.