Survival outcomes and prognostic value of nutritional and inflammatory markers in third-line treatment of metastatic pancreatic cancer.

[BACKGROUND] Metastatic pancreatic ductal adenocarcinoma (mPDAC) is one of the most aggressive malignancies with a very poor prognosis. Currently, there is no standardized therapeutic approach for third-line systemic treatment. The aim of this retrospective/prospective study was to evaluate survival outcomes in patients treated in the third-line setting and to analyze the impact of nutritional and inflammatory biomarkers on overall survival (OS) and progression-free survival (PFS).

[METHODS] The analysis retrospectively and prospectively included 95 patients with mPDAC treated with third-line systemic therapy. Data were collected from the Slovak Pancreas Registry. Data were collected from 13 hospitals. Baseline chemotherapy regimens, ECOG, nutritional, and inflammatory parameters were recorded and used to calculate prognostic scores (PNI, CRP, NLR, SII, SIRI, GPS). Their association with OS and PFS was analyzed using the log-rank test and Kaplan-Meier survival analysis.

[RESULTS] The most frequently used regimen was FOLFOX/CAPOX (56 patients), followed by nanoliposomal irinotecan (nal-IRI, 24 patients) and capecitabine (11 patients). The median OS was 5.55 months and the median PFS was 3.29 months. A PNI > 40.5 was significantly associated with longer OS (6.34 vs. 3.32 months,  = 0.001) and PFS (3.71 vs. 2.76 months,  = 0.009). Lower GPS scores were significantly associated with improved OS ( = 0.006) and PFS ( = 0.027). Other inflammatory markers (NLR, SIRI, SII, CRP) did not show a statistically significant impact on OS or PFS.

[CONCLUSION] Third-line systemic therapy may offer clinical benefit in selected mPDAC patients, particularly in those with favorable nutritional-inflammatory profiles. The Prognostic Nutritional Index (PNI) and Glasgow Prognostic Score (GPS) appear to be potentially useful tools for identifying candidates suitable for further systemic treatment. However, further prospective studies are needed to confirm these findings.