Retrospective study of impact of SPOP mutation on clinical outcomes in metastatic prostate cancer

Previous studies suggest that SPOP mutations result in increased sensitivity to androgen receptor pathway inhibitors (ARPIs). A retrospective study using the real-world clinicogenomic Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort database investigated outcomes of metastatic prostate cancer (mPC) based on SPOP mutation status. Among 2,097 mPC patients, 115 (5.5%) had SPOP-mutated tumors. Compared with SPOP wild-type, patients with SPOP mutations were older at diagnosis (p=0.001) and had higher (≥ 8) Gleason sum (p=0.02), higher incidence of lung metastasis (p=0.001), and increased frequency of intraductal features (p<0.001). SPOP mutations were associated with improved PSA90 response with first ARPI exposure in the castrate-resistant setting (60% versus 40.6%; OR 2.20; p=0.02) but not in the castrate-sensitive setting (78.9% versus 71.5%; OR 1.49; p=0.43). Median progression-free survival did not differ between SPOP-mutated versus wild-type group. In multivariable analysis, SPOP mutations were associated with improved overall survival (HR 0.65; p=0.02). The authors conclude that SPOP mutations were associated with longer overall survival despite the presence of aggressive clinical features.