EP1004 - Five-year review comparing pathologic tumor response to neoadjuvant treatment between young-onset and late-onset rectal cancer at the Philippine General Hospital

Purpose/Background: There has been a concerning rise in the incidence of colorectal cancer (CRC) among individuals under the age of 50—referred to as young-onset rectal cancer (YORC). These patients often present in advanced stages and are more likely to undergo neoadjuvant therapy. In this context, pathologic tumor response as an assessment of the degree of tumor regression in resected specimens following neoadjuvant therapy (NAT) has emerged as key prognostic indicator. Complete or near-complete, pathologic response (pCR) has been associated with improved disease-free and overall survival. However, data specifically examining pathologic response patterns in YORC remain limited.

Methods/Interventions: This is a single-institution, retrospective cohort study that included rectal cancer patients who underwent NAT followed by definitive surgery between January 2020 and December 2024. Patients were categorized as YORC ( < 50 years), or late-onset rectal (LORC ≥50 years) cancer. Baseline characteristics and pathologic outcomes were collected. The primary outcome was pathologic tumor response measured using the modified Ryan scheme. Statistical analysis to determine significance was done (p-value < 0.05).

Results/Outcomes: A total of 299 patients (mean age 57 years, range 22-82 years) were included, 79 (26.42%) YORC and 220 (73.58%) LORC. YORC cases in 2020 was 15.9%, and this doubled to 31.8% in 2024. Baseline characteristics and pathological outcomes showed no significant difference in both groups, as summarized in Table 1.
In terms of neoadjuvant regimens, LCCRT was the most frequently administered followed by RAPIDO protocol. The overall pCR rate was 18.39%. The pCR rate for the YORC and LORC groups were 32.91% and 24.09%, respectively. Comparative analysis showed no significant difference in the pCR rates for both groups (p = 0.1292). Fisher’s exact test revealed no significant between-group difference in pCR rate across different NAT regimens. Although YORC exhibited numerically higher response rates across most treatment regimens, none particularly demonstrated superior efficacy (p = 0.8696). Among LORC patients, pCR varied significantly across treatment types (p = 0.048), with LCCRT showing a significantly higher pCR rate (13.18%) compared to TNT regimens. Logistic regression analysis showed no significant interaction between age group and NAT type but showed associated with tumor differentiation (95% CI: 0.11-0.32, p < 0.001). After adjusting for NAT regimen, if each group received same treatment, the odds of achieving pCR was 1.55 times higher in YORC than in LORC (95% CI: 0.86-2.76, p = 0.14), indicating a non-significant trend favoring younger age.

Conclusion/Discussion: The incidence of YORC appears to continue to rise, accounting for a growing proportion of newly diagnosed cases. The present study found comparable characteristics between young and late-onset cohorts. Age was not a significant predictor of achieving pCR. Further multicenter studies with uniform treatment protocols are warranted to clarify to clarify the biologic and therapeutic distinctions of early-onset disease and optimize outcomes across age groups.