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

Ondřej Fiala; Michaela Tkadlecová; Zuzana Váchalová; Milan Hora; Jan Králíček; Petr Stránský; Václav Liška; Matteo Santoni; Giuseppe Luigi Banna; Kristýna Pivovarčíková; Ondřej Topolčan; Jindřich Fínek

doi:10.1002/pros.70197

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

Ondřej Fiala
, Michaela Tkadlecová
, Zuzana Váchalová
, Milan Hora
, Jan Králíček
, Petr Stránský
, Václav Liška
, Matteo Santoni
, Giuseppe Luigi Banna
, Kristýna Pivovarčíková
, Ondřej Topolčan
, Jindřich Fínek

School of Medicine, Pharmacy and Biomedical Sciences

Portsmouth Hospitals University NHS Trust

Research output: Contribution to journal › Article › peer-review

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Abstract

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/NSE₀) (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.

Original language	English
Journal	The Prostate
Early online date	26 May 2026
DOIs	https://doi.org/10.1002/pros.70197
Publication status	Early online - 26 May 2026

Keywords

androgen receptor signaling inhibitors
biomarker
castration‐resistant prostate cancer
neuron‐specific enolase
prognosis

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10.1002/pros.70197

Prognostic Role of Serum Neuron‐Specific EnolaseFinal published version, 1 MBLicence: CC BY-NC-ND

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Fiala, O., Tkadlecová, M., Váchalová, Z., Hora, M., Králíček, J., Stránský, P., Liška, V., Santoni, M., Banna, G. L., Pivovarčíková, K., Topolčan, O., & Fínek, J. (2026). 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. The Prostate. Advance online publication. https://doi.org/10.1002/pros.70197

@article{954f84cf8d204dcd8152c82bba0a1da4,

title = "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",

abstract = "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(NSE4w/NSE0) (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.",

keywords = "androgen receptor signaling inhibitors, biomarker, castration‐resistant prostate cancer, neuron‐specific enolase, prognosis",

author = "Ond{\v r}ej Fiala and Michaela Tkadlecov{\'a} and Zuzana V{\'a}chalov{\'a} and Milan Hora and Jan Kr{\'a}l{\'i}{\v c}ek and Petr Str{\'a}nsk{\'y} and V{\'a}clav Li{\v s}ka and Matteo Santoni and Banna, \{Giuseppe Luigi\} and Krist{\'y}na Pivovar{\v c}{\'i}kov{\'a} and Ond{\v r}ej Topol{\v c}an and Jind{\v r}ich F{\'i}nek",

year = "2026",

month = may,

day = "26",

doi = "10.1002/pros.70197",

language = "English",

journal = "The Prostate",

issn = "0270-4137",

publisher = "John Wiley and Sons Inc.",

}

Fiala, O, Tkadlecová, M, Váchalová, Z, Hora, M, Králíček, J, Stránský, P, Liška, V, Santoni, M, Banna, GL, Pivovarčíková, K, Topolčan, O & Fínek, J 2026, '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', The Prostate. https://doi.org/10.1002/pros.70197

TY - JOUR

T1 - 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

AU - Fiala, Ondřej

AU - Tkadlecová, Michaela

AU - Váchalová, Zuzana

AU - Hora, Milan

AU - Králíček, Jan

AU - Stránský, Petr

AU - Liška, Václav

AU - Santoni, Matteo

AU - Banna, Giuseppe Luigi

AU - Pivovarčíková, Kristýna

AU - Topolčan, Ondřej

AU - Fínek, Jindřich

PY - 2026/5/26

Y1 - 2026/5/26

N2 - 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(NSE4w/NSE0) (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.

AB - 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(NSE4w/NSE0) (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.

KW - androgen receptor signaling inhibitors

KW - biomarker

KW - castration‐resistant prostate cancer

KW - neuron‐specific enolase

KW - prognosis

U2 - 10.1002/pros.70197

DO - 10.1002/pros.70197

M3 - Article

SN - 0270-4137

JO - The Prostate

JF - The Prostate

ER -

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

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