Uptake of doublet and triplet therapy for men with de novo metastatic castration-sensitive prostate cancer. Population-based study.

[PURPOSE] In randomised clinical trials, doublet and triplet therapy improved survival compared to standard androgen deprivation therapy (ADT) in men with de novo metastatic castration-sensitive prostate cancer (mCSPC). Guidelines recommend doublet therapy since 2020 and triplet therapy since 2022. The aim of this study was to assess the uptake of upfront doublet and triplet therapy at a population level and assess trends in survival for all men with mCSPC.

[METHODS] We included men registered with de novo mCSPC in 2016-2024 in the National Prostate Cancer Register of Sweden. We estimated the annual proportion of men with de novo mCSPC who upfront received doublet therapy (ADT plus androgen receptor pathway inhibitor [ARPI] or docetaxel) or triplet therapy (ADT plus docetaxel and ARPI). Kaplan-Meier curves were used to estimate 3-year overall survival.

[RESULTS] In 9294 men diagnosed with de novo mCSPC, the use of upfront doublet therapy increased from 19% in 2016 to 66% in 2024, and the use of triplet therapy rose from 4% in 2021 to 17% in 2024. Uptake was highest among men below age 65 years, of whom 46% received doublet and 48% received triplet therapy in 2024. Three-year survival increased from 51% (95% CI: 49-52%) in 2016-2018 to 61% (95% CI: 58-64%) in 2022-2024. Among men below age 65, survival increased from 69% (95% CI: 65-73) in 2019-2021 to 77% (95% CI: 71-84) in 2022-2024.

[CONCLUSIONS] The uptake of doublet and triplet therapy increased substantially during the study period, in particular among men below age 65. In parallel, 3-year overall survival increased in all men diagnosed with de novo mCSPC. These data provide support for the benefit of upfront doublet or triplet therapy in clinical practice.