Clinical Characteristics and Survival Outcomes of a Clinically Defined Treatment-Emergent Neuroendocrine/Aggressive-Variant Prostate Cancer Phenotype: A Retrospective Study.

Background and

Objectives

Treatment-emergent neuroendocrine prostate cancer (t-NEPC) is an aggressive resistance phenotype arising during metastatic castration-resistant prostate cancer (mCRPC). Because metastatic biopsy is not routinely feasible in advanced disease, real-world data on clinically defined t-NEPC/aggressive-variant prostate cancer (AVPC)-like disease remain limited. We aimed to characterize the clinical features, treatment patterns, survival outcomes, and prognostic factors of this clinically defined phenotype. Materials and

Methods

We retrospectively reviewed 354 patients with prostate cancer treated at our institution between 2010 and 2020. Seventy-four patients with mCRPC who were clinically identified as having a t-NEPC/AVPC-like phenotype and had a treatment plan for platinum- and/or etoposide-based neuroendocrine-directed systemic therapy were included. Overall survival (OS) and radiographic progression-free survival (rPFS) were estimated using the Kaplan-Meier method, and prognostic factors were evaluated using Cox regression analyses.

Results

At clinical identification of the phenotype, the median age was 66.4 years, and visceral metastases were present in 67.6% of patients, most commonly in the liver (55.4%). Median intervals from prostate cancer diagnosis and CRPC onset to clinical identification of the phenotype were 47.5 and 22.7 months, respectively. Neuroendocrine-directed therapy was initiated in 72 patients; platinum-etoposide was the most common first-line regimen (n = 41, 55.4%). Median OS was 4.4 months (95% confidence interval [CI], 2.9-5.8), and median rPFS was 3.5 months (95% CI, 2.7-4.2). In an exploratory, unadjusted analysis, median OS did not differ significantly between doublet chemotherapy and monotherapy (7.0 vs. 3.5 months; p = 0.167). Gleason score ≥9, hemoglobin <12 g/dL, and albumin <3.5 g/dL were independently associated with inferior OS.

Conclusions

The clinically defined t-NEPC/AVPC-like phenotype was associated with an aggressive clinical course and poor survival. Earlier recognition, improved biomarker-based diagnostic strategies, and more effective therapeutic approaches are needed.