Real-world Clinical Outcomes and Prognostic Factors in Neuroendocrine Prostate Cancer

Neuroendocrine prostate cancer (NEPC) encompasses pure NEPC and tumors with mixed adenocarcinoma and neuroendocrine histology. While NEPC is thought to confer a poor prognosis, outcome data are sparse, making risk stratification and treatment decisions difficult for clinicians.

This retrospective study identified patients with morphological and/or immunohistochemical NEPC features on pathological review of high-grade prostate cancer cases. Median overall survival (OS) was calculated by stage and castration sensitivity. Prognostic factors were assessed via multivariate analysis. OS and progression-free survival on first-line metastatic systemic treatment were also evaluated.

Of 135 NEPC cases, 25.9% had NEPC documented in the original pathological report. Mixed pathology was found in 91.9% of cases. Median OS from NEPC diagnosis was 59.2, 42.3, 14.3, 17.6 and 9.6 months for localized, nonmetastatic castration-sensitive, nonmetastatic castration-resistant, metastatic castration-sensitive and metastatic castration-resistant prostate cancer, respectively. Anemia (hazard ratio [HR]: 1.66; 95% CI 1.05-2.16; P = .031) and elevated neutrophil-lymphocyte ratio (NLR) (HR: 1.51; 95% CI 1.01-2.52; P = .045), were associated with increased risk of death on multivariate analysis. 67 patients received first-line metastatic treatment beyond androgen deprivation, with a median progression-free survival of 5.2 months and OS of 15 months. Of these, 50.7% received more than 1 line of systemic treatment.

We observed underdiagnosis of NEPC in pathology specimens. NEPC is associated with poorer prognosis than would be expected in pure adenocarcinoma populations, with rapid progression on first-line metastatic treatment and sharp drop-off between subsequent treatment lines. Anemia and elevated NLR were associated with poor survival.