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Updated: Feb 12, 2026

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Outcomes for Patients With SPOP Mutated Castration-Resistant Prostate Cancer (CRPC) Treated With an Androgen Receptor

Joseph J Park1, Lauren E Howard2, Stamatina Fragkogianni3

  • 1Duke University Department of Medicine, Division of Medical Oncology, Durham, NC; Duke Cancer Institute, Center for Prostate and Urologic Cancers, Durham, NC.

Clinical Genitourinary Cancer
|February 10, 2026
PubMed
Abstract

Insights

SPOP mutations did not explain survival differences in castration-resistant prostate cancer (CRPC) by race, despite improving PSA declines. Black men showed improved overall survival (OS) with androgen receptor pathway inhibitor (ARPI) therapy in the CRPC setting.

Area of Science:

  • Oncology
  • Genetics
  • Prostate Cancer Research

Background:

  • SPOP gene mutations are linked to increased androgen receptor activity in hormone-sensitive prostate cancer.
  • The impact of SPOP alterations on outcomes in castration-resistant prostate cancer (CRPC), especially across racial groups, is not well understood.

Purpose of the Study:

  • To investigate the association between SPOP mutations, race, and treatment outcomes in patients with CRPC receiving first-line androgen receptor pathway inhibitor (ARPI) therapy.
  • To explore whether SPOP status mediates racial disparities in CRPC treatment response.

Main Methods:

  • Retrospective analysis of 78 SPOP-mutated (SPOPmut) and 223 SPOP wild-type (SPOPwt) CRPC patients treated with first-line ARPI.
  • Somatic gene profiling using next-generation sequencing (NGS) assays.
  • Comparison of PSA declines, time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS) stratified by SPOP status and race.

Main Results:

  • SPOP mutations were identified in 29% of Black men and 20% of White men.
  • No significant differences in TTF, PFS, or OS were observed based on SPOP status after adjusting for clinical factors.
  • Black men demonstrated significantly improved OS with first-line ARPI therapy, irrespective of SPOP status.
  • PSA declines (PSA90) were more frequent in SPOPmut patients (51% vs. 31%).
  • SPOP mutations were associated with AR ligand-binding domain mutations, APC, and CDKN1B alterations.

Conclusions:

  • SPOP mutations are not the primary driver of differential survival outcomes observed between Black and White men with CRPC treated with ARPIs.
  • While SPOP mutations correlate with better short-term PSA response, they do not appear to influence long-term survival in this setting.
  • Further research is needed to identify the factors contributing to the observed racial disparities in CRPC outcomes.
Keywords:
AbirateroneEnzalutamideGenomicsHormone sensitiveRace

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