Early age of onset is an independent predictor for worse disease-free survival in sporadic rectal cancer patients. A comparative analysis of 980 consecutive patients

Background: while interest on early-onset colorectal cancer (age ≤49) is on the rise, studies on early-onset rectal cancer (EORC) are limited. The aim of this study was to compare predictors for disease progression/recurrence between sporadic EORC and late-onset RC patients (LORC). Methods: 163 EORC and 830 LORC operated between January 1st, 2010 and April 30th, 2021 at a tertiary center were included. Demographics, tumor characteristics, microsatellite status, gene mutations (KRAS, BRAF, NRAS, PI3Kca) and oncologic outcomes were compared. A Cox proportional hazards regression analysis was performed to ascertain the effect of variables on recurrence/progression and death. Recurrence/Progression free survival (R/PFS) and cancer specific survival (CSS) were analyzed by the Kaplan-Meier estimator. Results: Mean age of EORC was 42.16, (46% aged 45-49). A majority of EORC patients had a family history for CRC (p = 0.01) and underwent total neoadjuvant treatment (p = 0.01). EORC patients showed a higher rate of low-grade tumor differentiation (p < 0.0001), stage III-IV (p = 0.001), microsatellite instability (p = 0.02), locoregional nodal (p = 0.001) and distant metastases (p < 0.0001). Accordingly, more EORC patients underwent adjuvant treatment (p < 0.0001). Mutations were mostly reported among LORC cases (p = 0.04), whereas EORC patients showed a worse R/PFS (p = 0.02), even at stage I (p = 0.04). CSS did not differ (p = 0.11) across groups. Multivariate analysis indicated age of onset (p = 0.04) was an independent predictor for progression/recurrence. Conclusions: Age of onset was shown to be an independent unfavorable predictor. Delayed diagnosis could explain this effect in the more advanced stages, while the worse outcomes in stage I may suggest a more aggressive disease behavior.