Background: Significant lack of treatment (Tx) intensification is seen in clinical practice for pts with mHSPC until progression to mCRPC. The TRUMPET registry enabled a post-hoc analysis of clinical outcomes in pts with mCRPC, initially diagnosed with de novo mHSPC vs nmHSPC. Methods: TRUMPET, a prospective, observational study of US pts with CRPC, enrolled male adults (03/2015-09/2018) who began first or second-line Tx for M0/M1 CRPC. For this post hoc, pts with M1 CRPC at enrollment initially diagnosed with de novo mHSPC (clinical TNM1 stage) were compared to M1 CRPC pts initially diagnosed with nmHSPC (clinical TNM0 stage). Clinical outcomes (radiographic progression-free survival [rPFS], prostate specific antigen [PSA] progression, time to opiate initiation [OI], mortality) were analysed with Kaplan–Meier and Cox proportional hazards models. An exploratory subanalysis investigated outcomes in de novo mHSPC pts who received Tx intensification (docetaxel or abiraterone) with androgen-deprivation therapy (ADT) as primary Tx prior to mCRPC vs pts who did not. Results: M1 CRPC pts initially diagnosed with de novo mHSPC (n = 199) or nmHSPC (n = 254) were included; median age: 70.0 vs 73.0 years, duration from initial PC diagnosis to baseline mCRPC visit: 1.62 vs 6.72 years, PSA at PC diagnosis: 113.1 vs 10.1 ng/mL, Gleason score: 9.0 vs 8.0, respectively. In the de novo mHSPC and nmHSPC groups, initial CRPC Tx was chemotherapy in 9.0% vs 5.9% of pts, novel hormonal therapy (enzalutamide or abiraterone) in 55.3% vs 59.1%, immunotherapy in 35.2% vs 42.9%, respectively. No differences were seen in rPFS or PSA progression (table). The de novo mHSPC group showed a trend toward shorter time to OI and significantly increased risk of mortality (37%) with 6.6 months shorter median survival vs nmHSPC. The subanalysis included 44 (22.1%) de novo mHSPC pts who received Tx intensification with ADT at initial diagnosis. A trend towards improved survival was seen in the Tx-intensified vs nonintensified subgroup (median time to death [95%CI]; 47.7 months [22.18, NE] vs 37.3 months [28.35, 43.01]). Conclusions: At mCRPC diagnosis, pts with de novo mHSPC have significantly higher mortality risk than pts with nmHSPC, indicating a need to delay progression of de novo mHSPC to mCRPC. The trend for improved survival benefit in pts with Tx-intensified de novo mHSPC further underlines the need for early Tx intensification.

^*Reference NE: not estimable.