The Prognostic Role of the Lung Immune Prognostic Index in Neuroendocrine Prostate Cancer: A Multicenter Retrospective Study

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Abstract
Background: Neuroendocrine prostate cancer (NEPC) is a rare and aggressive malignancy with limited prognostic tools. The Lung Immune Prognostic Index (LIPI), derived from dNLR and lactate dehydrogenase, has demonstrated prognostic value in small-cell lung cancer but has not been evaluated in NEPC. This study assessed the prognostic role of LIPI in NEPC. Methods: This multicenter retrospective study included 34 patients with NEPC (21 secondary, 13 de novo) from four centers in Turkey. Laboratory data were collected at NEPC diagnosis (T3), initial prostate cancer diagnosis (T1), and castration-resistant prostate cancer diagnosis (T2). LIPI was scored using original fixed cut-offs. Survival analyses included Kaplan–Meier, Cox regression, and ROC methods. Results: At NEPC diagnosis, 18 patients (52.9%) had Good LIPI and 16 (47.1%) Intermediate + Poor LIPI. Intermediate + Poor LIPI was associated with significantly shorter overall survival (median 4 vs. 15 months; log-rank p = 0.001; HR 3.83, 95% CI 1.65–8.90). In multivariable analysis, albumin was an independent predictor (HR 0.37, p = 0.015), while LIPI showed a trend (HR 2.35, p = 0.091). LIPI demonstrated the highest discriminatory ability for 6-month overall survival (AUC 0.763, p = 0.009). LIPI at earlier disease stages did not predict time to transformation or castration resistance. Among secondary NEPC patients, worsening LIPI trajectory was associated with shorter survival (median 4 vs. 10 months; log-rank p = 0.031). Conclusions: LIPI at NEPC diagnosis was associated with overall survival and demonstrated the highest discriminatory ability among the inflammatory indices assessed. As a routine blood-based score, LIPI may support risk stratification at NEPC diagnosis. Prospective validation is warranted.

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