SPOP Mutations as a Predictive Biomarker for Androgen Receptor Axis–Targeted Therapy in De Novo Metastatic Castration-Sensitive Prostate Cancer

Umang Swami, Ryon P. Graf, Roberto H. Nussenzveig, Virginia Fisher, Hanna Tukachinsky, Alexa B. Schrock, Gerald Li, Jeffrey S. Ross, Nicolas Sayegh, Nishita Tripathi, Vinay Mathew Thomas, Geoffrey R. Oxnard, Emmanuel S. Antonarakis, Neeraj Agarwal

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Purpose: Intensification of androgen deprivation therapy (ADT) with either docetaxel or androgen receptor axis–targeted therapies (ARAT) are the current standard of care for patients with metastatic castration-sensitive prostate cancer (mCSPC). However, biomarkers guiding treatment selection are lacking. We hypothesized that ADT intensification with ARAT, but not with docetaxel, would be associated with improved outcomes in patients with de novo (dn)mCSPC harboring SPOP mutations. Experimental Design: Patient-level data from a deidentified nationwide (U.S.-based) prostate cancer clinico-genomic database between January 2011 and December 2021 were extracted. Eligibility criteria: diagnosis of metastatic disease within 30 days of original prostate cancer diagnosis, genomic profiling of a tissue biopsy collected within 90 days of original diagnosis, and initiation of ARAT or docetaxel within 120 days of initial diagnosis. The log-rank test and Cox proportional hazards models were used to compare time to castration-resistant prostate cancer (TTCRPC) and overall survival (OS) for patients with and without SPOP mutations undergoing ADT intensification with ARAT or docetaxel. Results: In the ARAT cohort, presence of SPOP mutation compared with wild-type was associated with more favorable TTCRPC [not reached (NR) vs. 16.7 months; adjusted HR (aHR), 0.20; 95% confidence interval (CI), 0.06–0.63; P ¼ 0.006] and OS (NR vs. 27.2 months; aHR, 0.19; 95% CI, 0.05–0.79; P ¼ 0.022). In contrast, SPOP mutation status was not associated with TTCRPC or OS in docetaxel-treated cohort. Conclusions: In real-world settings, SPOP mutations were associated with improved outcomes to ADT plus ARAT (but not ADT plus docetaxel) in patients with dn-mCSPC. This may serve as a predictive biomarker to guide treatment selection for patients with mCSPC.

Original languageEnglish (US)
Pages (from-to)4917-4925
Number of pages9
JournalClinical Cancer Research
Issue number22
StatePublished - Nov 15 2022

Bibliographical note

Funding Information:
We thank the patients whose data made this research possible, the clinical and laboratory staff at Foundation Medicine, and the team at Flatiron Health. This study was supported by Foundation Medicine.

Publisher Copyright:
©2022 American Association for Cancer Research.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


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