Prognostic Role of Serum Neuron‐Specific Enolase at Baseline and its Early Dynamics in Metastatic Castration‐Resistant Prostate Cancer Treated With Androgen Receptor Signaling Inhibitors

Background Outcomes of metastatic castration‐resistant prostate cancer (mCRPC) treated with androgen receptor signaling inhibitors (ARSIs) vary widely and may not be fully reflected by PSA and standard clinicopathologic factors. We evaluated the prognostic value of serum neuron‐specific enolase (NSE) at baseline and early on‐treatment dynamics. Methods We retrospectively analyzed ARSI‐treated mCRPC patients with available baseline NSE (n = 120). NSE was dichotomized by the upper limit of normal (ULN, 12.5 ng/mL). Radiographic progression‐free survival (rPFS) and overall survival (OS) were estimated by Kaplan–Meier methods and compared by log‐rank test. Multivariable Cox models adjusted for age, baseline PSA (per 100 ng/mL), line of therapy (2–4 vs 1), Gleason score (> 7 vs ≤ 7), metastatic timing (synchronous vs metachronous), and visceral metastases (present vs absent). NSE dynamics were evaluated using a 28‐day landmark approach among patients alive and at risk at day 28 with available baseline and week‐4 NSE (rPFS landmark n = 47; OS landmark n = 48); follow‐up was redefined from day 28 and dynamics were modeled as log2(NSE 4w /NSE 0 ) (per doubling). Results Median follow‐up was 44.7 months (95% CI 35.7–48.3). Baseline NSE > ULN was associated with shorter rPFS (9.4 vs 20.8 months) and OS (23.5 vs 38.2 months). In multivariable analyses, baseline NSE > ULN remained independently associated with inferior outcomes (rPFS HR 1.81, 95% CI 1.15–2.85, p = 0.011; OS HR 1.85, 95% CI 1.12–3.05, p = 0.017). In landmark models, higher NSE dynamics were independently associated with worse outcomes (rPFS HR 4.30, 95% CI 1.06–17.39, p = 0.041; OS HR 8.78, 95% CI 2.15–35.77, p = 0.002). Conclusions In ARSI‐treated mCRPC, baseline NSE above ULN and early 4‐week NSE dynamics provide independent prognostic information for rPFS and OS, supporting NSE as a pragmatic adjunct to clinical risk stratification.