Clinicopathologic features and overall survival of patients with early-onset colorectal cancer in a South African cohort study.

58 Background: The incidence of early-onset colorectal cancer (EOCRC) has increased across sub-Saharan Africa, but data describing the features of EOCRC in this region is limited. We characterized the demographics, clinicopathologic features, and survival outcomes of EOCRC patients in South Africa (SA). Methods: The Colorectal Cancer in South Africa (CRCSA) study is a longitudinal cohort study that enrolled CRC patients from five academic teaching hospitals affiliated with the University of the Witwatersrand between 2016 and 2019. We excluded patients with known mismatch repair deficiency and treated patients with multiple primary tumors as distinct cases. We stratified the cohort by age at CRC diagnosis (<50 vs ≥50 years) and performed a multivariable Cox proportional hazards analysis to compare overall survival (OS) between EOCRC and average-onset CRC (AOCRC). We performed a principal component analysis of self-reported diet data to identify dietary patterns and used a multivariable linear regression model to test the association of diet with age at CRC diagnosis. Results: In our cohort of 704 CRC cases, 179 were EOCRC (25.4%). EOCRC accounted for a greater proportion of CRC cases in Black patients than in non-Black patients (32.1% vs 18.4%, p < 0.001). Rectal cancer accounted for 55.8% of all tumors with no difference by age at diagnosis (p = 0.737). Metastatic disease was present at diagnosis in 47.4% of EOCRC cases and 38.0% of AOCRC cases (p = 0.042). EOCRC tumors were more likely to be KRAS WT (78.6% of EOCRC vs 48.3% of AOCRC, p = 0.041), although only 10% of tumors were tested. In a multivariable Cox proportional hazards model, EOCRC was not associated with OS (adjusted HR 1.12; 95% CI 0.88-1.42). Black race (adjusted HR 1.43; 95% CI 1.13-1.81) and male gender (adjusted HR 1.46; 95% CI 1.17-1.82) were associated with worse OS. In a multivariable linear regression model, patients in the highest quartile of adherence to a Western diet were diagnosed 4.19 years earlier than those in the lowest quartile (p = 0.005). Conclusions: In SA, EOCRC and AOCRC have comparable presentations, although EOCRC is more common in Black South Africans and is more likely to present with metastatic disease. Survival outcomes are similar across age groups after adjusting for relevant factors. Increased adoption of a Western diet may contribute to the rising burden of EOCRC in SA, but larger prospective studies of lifestyle factors are needed. Multivariable Cox regression model evaluating the association of age at CRC diagnosis with overall survival in the Colorectal Cancer in South Africa (CRCSA) study (2016-2019). Hazard Ratio* (95% CI)(n = 578) Age at Diagnosis Early-Onset 1.12 (0.88-1.42) Average-Onset 1.00 Race Black 1.43 (1.13-1.81) Non-Black 1.00 Gender Male 1.46 (1.17-1.82) Female 1.00 *The model also adjusted for BMI, socioeconomic status, and stage at diagnosis (data not shown).