Clinical and genomic features of SPOP -mutant prostate cancer
The Prostate — Nakazawa M, Fang M, Marshall CH, et al. | November 17, 2021
In SPOP-mutant prostate cancers (a unique subset), ERG fusions are absent and Wnt pathway alterations occur frequently. These cancers showed potentially greater dependency on androgen signaling and enhanced responsiveness to androgen deprivation therapy (ADT). Best results are obtained in SPOP-altered patients without other concurrent mutations.
A retrospective analysis of 72 consecutive prostate cancer patients with somatic SPOP mutations who were treated at the Johns Hopkins Hospital, to assess clinical as well as genomic characteristics of this SPOP-mutant subset.
SPOP-mutant malignancies seemed to be mutually exclusive with tumors harboring the TMPRSS2-ERG fusion, and were found to be significantly enriched for Wnt pathway (APC, CTNNB1) mutations and de-enriched for TP53/PTEN/RB1 alterations.
Durable responses to ADT were noted in patients with mtSPOP; the median time-to-castration-resistance was 42.0 months.
However, significantly shorter time-to-castration-resistance was observed in SPOP-mutant cases with concurrent TP53 mutations (hazard ratio [HR] 4.53), HRD pathway (ATM, BRCA1/2, and CHEK2) mutations (HR 3.19), and PI3K pathway (PTEN, PIK3CA, and AKT1) alterations (HR 2.69).
Abiraterone and enzalutamide offered median progression-free survival of 8.9 months and 7.3 months, respectively, in the castration-resistant prostate cancer setting.
No responses were seen for PARP inhibitor treatment.
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