Prognostic factors for rapid progression in metastatic pancreatic adenocarcinoma: Clinical, histopathological, and laboratory analysis.

Abstract

681 Background: Metastatic pancreatic adenocarcinoma (mPAC) remains highly lethal despite modern chemotherapy. Outcome heterogeneity underscores the need for pragmatic prognostic markers. Rapid progression (RP)—progression within six months of first-line therapy—may reflect primary resistance but is under-characterized in real-world Brazilian cohorts. We evaluated clinical, histopathologic, and laboratory factors associated with RP and their impact on survival. Methods: We performed a single-center retrospective cohort at AC Camargo Cancer Center including 164 adults with histologically confirmed mPAC who initiated first-line chemotherapy between January 2021 and January 2024. Baseline variables included demographics, Charlson index, BMI, ECOG, primary tumor site, metastatic burden and sites, ascites (at diagnosis and during follow-up), histologic grade, neutrophil-to-lymphocyte ratio (NLR), albumin, and C-reactive protein (CRP). First-line regimens were FOLFIRINOX, gemcitabine+nab-paclitaxel, or gemcitabine-based. RP was defined as clinical/radiologic progression <6 months. Endpoints: progression-free survival (PFS) and overall survival (OS) by Kaplan–Meier with log-rank tests; Cox regression assessed associations with OS. Two-sided p<0.05 was significant. Results: RP occurred in 50.3% (82/163). Patients with RP had inferior outcomes: median PFS 4.0 months (95%CI 3.42–4.58) vs 7.0 months (95%CI 6.05–7.95; p<0.001) and OS 9.0 months (95%CI 7.47–10.53) vs 13.0 months (95%CI 11.37–14.64; p=0.003), compared with those without RP. In the overall cohort, median PFS was 5.0 months (95%CI 4.41–5.59) and median OS was 11.0 months (95%CI 10.03–11.97). Ascites at diagnosis (30.5% vs 17.3%, p=0.048) and at any time (73.2% vs 55.6%, p=0.019), as well as treatment de-escalation (91.0% vs 66.2%, p=0.001), were significantly more frequent among RP patients. No significant associations with RP were observed for age, sex, ECOG, NLR (cutoffs 2.2 and 4), albumin <4 g/dL, elevated CRP, histologic grade, BMI, number of metastatic sites, or primary tumor location. In multivariable Cox regression, RP remained an independent predictor of higher mortality (HR 1.71, 95%CI 1.14–2.58, p=0.010). Conclusions: In this real-world mPAC cohort, rapid progression was frequent and independently associated with worse survival. Ascites and treatment de-escalation emerged as accessible clinical markers of RP. Incorporating these parameters into baseline assessment, and potentially adding biomarker-driven tools in the future, may refine risk stratification and guide individualized therapeutic strategies.