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OLDER AGE DECREASES THE LIKELIHOOD OF SIGNIFICANT PATHOLOGIC RESPONSE IN PATIENTS WITH PDAC FOLLOWING NEOADJUVANT THERAPY
Victor Perim
*, K K. Akinola, Chandler McLeod, Herbert Chen, Smita Bhatia, John Bart B. Rose, Andrea Gillis
Department of Surgery, University of Alabama at Birmingham (UAB), Birmingham, AL
BACKGROUND: Neoadjuvant therapy (NAT) has been shown to improve survival in patients with pancreatic adenocarcinoma (PDAC), but there is ongoing debate about which patient population benefits the most. While a significant pathological response (SPR) is rare, it has been linked to improved survival. However, its impact on older adults remains underexplored. This study aims to identify the patient characteristics that most strongly predict the achievement of SPR following NAT stratified by age.
METHODS: Using the National Cancer Database (NCDB) 2022 dataset, we analyzed patients 30 and older diagnosed with PDAC (ICD-O-3: 8140 & 8500) who received NAT followed by surgery with or without adjuvant therapy from 2018 to 2022. A SPR was defined as pathologic stage of ypT0N0M0 or ypTisN0M0. Patients were stratified into tertiles age groups for analysis. The primary outcome was the incidence of SPR. Univariate and multivariate analyses were performed using SPR as the dependent variable. A confidence interval of 95% was used.
RESULTS: A total of 8,953 patients were included, 4,426 (49%) females, 82% non-Hispanic White, and with a mean age of 65.5 years (SD 9.34). Age group distribution was 3,150 (35.18%) aged 30–62, 2,943 (32.87%) aged 62–70, 2,860 (31.94%) aged 70–90. Charlson-Deyo Comorbidity Condition (CDCC) scores ?2 was observed more frequently in older age groups (9.3%, 12.6%, and 12.7%, respectively; p < 0.001), and advanced-stage disease (stage III/IV) was less common with increasing age (19.1%, 18.1%, and 15%; p < 0.001). SPR was achieved in 303 patients (3.4%). In univariate logistic regression, older age was associated with lower odds of achieving SPR compared to the reference group aged 30–62 years (62–70 years: OR 0.84 [95% CI: 0.64–1.09]; 70–90 years: OR 0.65 [95% CI: 0.48–0.86]; p < 0.01). In multivariate analysis, adjusting for demographics, tumor stage, chemotherapy regimen, and comorbidities, age 70–90 years remained a significant predictor of reduced SPR (OR 0.54 [95% CI: 0.34–0.83]; p < 0.01). Age-stratified multivariable survival analysis using Cox regression showed that achieving a significant pathological response was associated with significantly improved survival across all age groups: 30–62 years (HR 0.24 [0.12–0.46]; p < 0.001), 62–70 years (HR 0.32 [0.16–0.65]; p < 0.001), and 70–90 years (HR 0.33 [0.17–0.67]; p < 0.01).
CONCLUSION: Older patients with PDAC are significantly less likely to achieve SPR despite undergoing aggressive neoadjuvant therapy and surgery. Nevertheless, SPR remains a robust predictor of improved survival. Future studies should optimize NAT for older patients and explore other potentially biologic prognostic factors.
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