Real-world retrospective cohort study of three conversion therapy regimens for unresectable locally advanced pancreatic cancer: a single-center 5-year analysis focused on conversion resection rate and survival outcomes.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is mostly unresectable at initial diagnosis. Conversion therapy has become core treatment to downstage tumors for radical resection, yet consensus on optimal first-line regimen remains lacking. This real-world study compared three mainstream conversion regimens and identified independent survival predictors to guide individualized treatment. METHODS: A single-center retrospective cohort of 172 unresectable LAPC patients receiving gemcitabine plus nab-paclitaxel (AG), modified FOLFIRINOX (mFOLFIRINOX), or AG sequential chemoradiotherapy (CRT) from 2019 to 2023 was enrolled. Tumor conversion, surgical, survival and safety outcomes were analyzed. Cox regression was adopted to screen independent prognostic factors, with P<0.05 defined as statistical significance. RESULTS: The overall conversion rate reached 38.4%. mFOLFIRINOX yielded the highest conversion rate (52.8%) versus AG (32.6%) and AG + CRT (33.3%). Among 66 converted patients, 87.9% achieved R0 resection, with 34.8% major pathological response (MPR). Median overall survival (OS) of converted patients reached 32.5 months, far superior to non-converted cases (12.3 months). Multivariate analysis confirmed preoperative carbohydrate antigen 19-9 (CA19-9) normalization and prognostic nutritional index (PNI) ≥41.7 as two independent favorable prognostic markers. Grade 3-4 adverse events were most frequent in the mFOLFIRINOX group (56.6%). CONCLUSIONS: For physically fit unresectable LAPC patients, mFOLFIRINOX provides superior conversion efficacy despite higher toxicity. Normalized CA19-9 and well-maintained nutritional status are reliable prognostic biomarkers. This real-world evidence supports mFOLFIRINOX as preferred first-line conversion regimen and routine monitoring of CA19-9 and nutrition during therapy.