EP792 - Early-Onset Locally Advanced Rectal Cancer: Rates and Predictors of Pathological Complete Response

Purpose/Background: The incidence of early-onset rectal cancer is rising and frequently presents at a more advanced stage at the time of diagnosis. Current National Comprehensive Cancer Network guidelines recommend total neoadjuvant treatment for all locally advanced rectal cancers, with studies showing a pathologic complete response rate of approximately 20-40%. However, data remains conflicting on whether early-onset rectal cancer patients (defined as age < 50 years old at diagnosis) exhibit different pathologic complete response rates compared to rectal cancer patients diagnosed after the age of 50. This study aimed to compare the pathologic complete response rates of locally advanced rectal cancer following treatment with neoadjuvant therapy and proctectomy between early-onset patients and patients diagnosed after the age of 50. Our hypothesis was that early-onset rectal cancer patients will have a decreased proportion of pathologic complete response relative to patients diagnosed after the age of 50.

Methods/Interventions: We queried the National Cancer Database for all adults aged 18-89 years diagnosed with primary, non-metastatic, stage II/III, rectal adenocarcinoma who underwent total neoadjuvant treatment or neoadjuvant radiotherapy followed by total mesorectal excision between 2004-2022. Patients with missing pathological T and N staging data were excluded. Statistical analyses included univariate comparison of pathologic complete response rates between cohorts and multivariable logistic regression to identify factors associated with pathologic complete response.

Results/Outcomes: A total of 74,857 patients met inclusion criteria; 15,367 (20.5%) were diagnosed before the age of 50 and 59,490 (79.5%) were diagnosed after the age of 50. Overall, 11,083 patients (14.8%) achieved a complete pathologic response. There was no significant difference in achievement of pathologic complete response between the two groups, 2,271 (14.8%) for the early-onset group and 8,812 (14.8%) for the group diagnosed after the age of 50 (p=0.915). However, factors that increased pathologic complete response included female sex (OR 1.10 [1.06-1.15]), greater than median household income (OR 1.06 [1.00-1.12]), increasing time from neoadjuvant to surgery (OR 1.00 [1.00-1.00]) and factors that decreased pathologic complete response included black race (OR 0.86 [0.79-0.93]), uninsured or governmental insurance (OR 0.70 [0.62-0.79], OR 0.91 [0.87-0.95]), areas where the proportion of individuals without a high school degree exceeded 9% (OR 0.94 [0.90-0.99]), stage III rectal cancer (OR 0.87 [0.83-0.91]), mucinous histology (OR 0.20 [0.16-0.25]), radiotherapy only (OR 0.57 [0.50-0.65]), presence of lymphovascular invasion (OR 0.56 [0.50-0.62]) (Table 1).

Conclusion/Discussion: Our analysis reveals that early-onset rectal cancer patients have similar rates of pathologic complete response compared to their counterparts that are diagnosed after the age of 50 following neoadjuvant treatment and surgery. Importantly, disparities in socioeconomic status, race, and treatment modalities appear to influence the pathologic complete response rates, indicating that addressing these factors could be crucial for optimizing and improving outcomes in locally advanced rectal cancer.

Table 1
Multivariable logistic regression analysis for factors associated with pathologic response in locally advanced rectal cancer.