Age Matters: Early-Onset Rectal Cancer Exhibits Higher Rates of Pathological Complete Response: A Retrospective Analysis of the Influence of Young Age on Treatment Success in Stage II-III Rectal Cancer.

Background: The incidence of rectal cancer has decreased overall, but the incidence of early-onset rectal cancer (eoRC) has increased. Early-onset rectal cancer and late-onset rectal cancer (loRC) differ due to phenotypical, genetic characteristics, and higher stage presentations in eoRC. Thus, eoRC patients undergo more aggressive neoadjuvant treatments. This paper was designed to evaluate the impact of age on the pathological complete response rates in sporadic locally advanced rectal cancer.

Methods: All patients with stage II-III rectal cancer who underwent neoadjuvant therapy and curative rectal resection between January 2018 and December 2023 were included and allocated to eoRC (<50 years) and loRC (≥50 years) groups based on their age at diagnosis.

Results: A total of 381 patients were included (93 eoRC and 288 loRC). Preoperative radiological imaging revealed higher clinical nodal staging in the eoRC group (p = 0.002). A higher proportion of eoRC resulted in a pathological complete response compared with loRC (29% vs. 18.8%, p = 0.035). The rate of pathological complete response in eoRC and loRC did not differ between patients treated by total neoadjuvant therapy (TNT) and those treated by standard chemoradiotherapy (29.2% vs. 28.6%, p = 0.95 in eoRC and 21.7% vs. 25.9%, p = 0.097 in loRC). Multivariable analysis resulted in young age of onset (odds ratio 2.68; 95% confidence interval 1.11-6.51; p = 0.029) and KRAS wildtype (odds ratio 3.37; 95% confidence interval 1.25-9.07; p = 0.016) as being independent predictors of pathological complete response.

Conclusions: Sporadic eoRC and KRAS wildtype tumors are predictive factors for pathological complete response in stage II-III rectal cancer.