Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer

• DOI: 10.1016/j.annonc.2023.04.515
• Publication Date: 2023-05-09T01:01:28Z
• Authors: P.A. Sutera; A.C. Shetty; A. Hakansson; K. Van der Eecken; Y. Song; Y. Liu; J. Chang; V. Fonteyne; A.A. Mendes; N. Lumen; L. Delrue; S. Verbeke; K. De Man; Z. Rana; T. Hodges; A. Hamid; N. Roberts; D.Y. Song; K. Pienta; A.E. Ross; F. Feng; S. Joniau; D. Spratt; S. Gillessen; G. Attard; N.D. James; T. Lotan; E. Davicioni; C. Sweeney; P.T. Tran; M.P. Deek; P. Ost
• Keywords: Clinical endpoint; Localized disease

•Synchronous metastatic CSPC is associated with lower AR activity than metachronous disease.•Patients synchronous derive a greater benefit to combination plus non AR-based therapy.•Clinical and biologic differences between metastasis are most prominent in low-volume disease. BackgroundMetastatic castration-sensitive prostate cancer (mCSPC) commonly classified into high- subgroups which have demonstrated differential biology, prognosis, response therapy. Timing of has similarly clinical outcomes; however, less known about any underlying these disease states. Herein, we aim compare transcriptomic mCSPC identify responses therapy.Patients methodsWe performed an international multi-institutional retrospective review men who completed RNA expression profiling evaluation their primary tumor. Patients were stratified according timing (synchronous versus metachronous). The endpoint was profiles timing. median scores groups compared the Mann–Whitney U test. Secondary analyses included determining variables overall survival (OS) from time metastasis. Survival analysis carried out Kaplan–Meier method multivariable Cox regression.ResultsA total 252 patients follow-up 39.6 months. experienced worse 5-year OS (39% 79%; P < 0.01) androgen receptor (AR) (11.78 12.64; hallmark (HAR; 3.15 3.32; 0.01). Multivariable regression identified only high-volume [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; 0.01] HAR score (HR 0.51, CI 0.28-0.88; 0.02) significantly OS. Finally, 0.47, 0.30-0.72; but not 1.37, 0.50-3.92; 0.56) found better non-AR therapy as monotherapy (P value for interaction 0.05).ConclusionsWe potential difference mCSPC. Specifically, disease, those more hormone-dependent transcriptional profile exhibit prognosis Metastatic We regression. A 0.05).