Journal article
Impact of SPOP Mutations on Clinical Outcomes in Metastatic Prostate Cancer
JCO precision oncology, Vol.9, e2500590
12/2025
DOI: 10.1200/PO-25-00590
PMID: 41348987
Abstract
Purpose
Previous studies suggest that SPOP mutations result in increased sensitivity to androgen receptor pathway inhibitors (ARPIs) but are limited by lack of granular data. We hypothesize that SPOP mutations are associated with improved outcomes across the spectrum of advanced prostate cancer (PC).
Methods
Using the real-world clinicogenomic Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort database, we analyzed outcomes based on SPOP mutation status. The primary end point was overall survival (OS) from the diagnosis of metastatic disease. Secondary end points included real-world progression-free survival (PFS) and PSA90 response.
Results
Among 2,097 patients with metastatic PC, 5.5% (N = 115) had SPOP-mutated tumors. Compared with SPOP wild-type, patients with SPOP mutations were older at diagnosis (median 65 v 63 years; P = .001) and had higher (≥8) Gleason sum (68% v 54%; P = .02), higher incidence of lung metastasis (17% v 6%; P = .001), and increased frequency of intraductal features (13% v 5%; P < .001). SPOP mutations were associated with improved PSA90 response with first ARPI exposure in the castrate-resistant setting (60% v 40.6%; OR, 2.20 [95% CI, 1.15 to 4.19]; P = .02) but not in the castrate-sensitive setting (78.9% v 71.5%; OR, 1.49 [95% CI, 0.66 to 3.37]; P = .43). Median PFS with first ARPI did not differ in SPOP-mutated versus wild-type group in both the castrate-sensitive (24.2 v 19.2 months; hazard ratio [HR], 0.80 [95% CI, 0.49 to 1.32]; P = .39) and castrate-resistant settings (15.0 v 12.4 months; HR, 0.81 [95% CI, 0.58 to 1.12]; P = .20). In multivariable analysis, SPOP mutations were associated with improved OS (HR, 0.65, P = .02).
Conclusion
SPOP mutations were associated with longer OS despite the presence of aggressive clinical features. The distinct clinical and molecular features of SPOP-mutated PC support its consideration as a unique molecular subtype with prognostic implications.
Details
- Title: Subtitle
- Impact of SPOP Mutations on Clinical Outcomes in Metastatic Prostate Cancer
- Creators
- Deepak Kilari - Medical College of WisconsinNicholas C Henderson - University of MichiganKyra Yamamoto - University of California San DiegoYe Yao - University of California San DiegoClara Hwang - Ford Motor CompanyPedro C Barata - University Hospitals Seidman Cancer CenterMehmet Asim Bilen - Winship Cancer InstituteLaura Graham - University of Colorado Anschutz Medical CampusRohan Garje - Baptist Health South FloridaShoshana Rothstein - The Barbara Ann Karmanos Cancer InstituteShabi Haider - Medical College of WisconsinJoseph J Park - Duke Medical CenterRuben Raychaudhuri - Fred Hutch Cancer CenterAmanda Pilling - Ford Motor CompanyErica Chin - University of MichiganVadim S Koshkin - UCSF Helen Diller Family Comprehensive Cancer CenterAbhishek Tripathi - City Of Hope National Medical CenterFrank Cameron Cackowski - Wayne State UniversityJones T Nauseef - Cornell UniversityAlexandra Sokolova - University of PortlandAdanma Ayanambakkam - University of Oklahoma Health Sciences CenterYousef Zakharia - Mayo ClinicMichael Thomas Schweizer - University of WashingtonAndrew J Armstrong - Duke Medical CenterTanya B Dorff - City Of Hope National Medical CenterZachery Roger Reichert - University of California San DiegoRana R McKay - University of California San Diego
- Resource Type
- Journal article
- Publication Details
- JCO precision oncology, Vol.9, e2500590
- DOI
- 10.1200/PO-25-00590
- PMID
- 41348987
- eISSN
- 2473-4284
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
- Language
- English
- Date published
- 12/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985090398502771
Metrics
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