Abstract
Background
Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC.
Methods
A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified. Based on their initial disease burden and duration on ADT for HSPC, primary progressive (PP) men were classified into four groups: low/intermediate-risk localized disease (LOC) and high-risk localized/locally advanced disease (LAD) and short-term (ST) < 24 vs. long-term (LT) ADT ≥ 24 months, whereas de novo (DN) mHSPC were subdivided into short-time vs. long-time to CRPC.
Results
We included 919 mCRPC patients with a median age of 77 years [interquartile range (IQR) = 71–82)]. Median ADT duration in HSPC was 24 months (IQR = 14–40). Median follow-up was 91 months (IQR = 62–138), median OS and PFS from ARSI start were 20 (IQR 10–32) and 10 months (IQR = 5–19), respectively. In PP developing metastatic disease (n = 655, 71.3%), LOC and LAD with ST ADT had a greater than almost double-risk of death compared to LT ADT (LOC/ST: hazard ratio [HR] = 2.01; 95% CI 1.54–2.64; LAD/ST: HR = 1.73; 95% CI 1.34–2.24; p < 0.001). In the multivariate analysis including age, prognostic cohort, Gleason, ECOG, radical radiotherapy and prostatectomy, groups with ST ADT were associated with worse OS compared to LT ADT (LOC/ST: HR = 1.84; 95% CI 1.38–2.45; p < 0.001; LAD/ST: HR = 1.59; 95% CI 1.21–2.10; p < 0.001), along with ECOG > 2 (HR = 1.55; 95% CI 1.06–2.26; p = 0.03). There were also similar results of PFS. Moreover, long-time to CRPC in patients with history of DN mHSPC (n = 264, 28.7%) resulted in a better OS/PFS (HR = 0.76, 95% CI 0.56–1.02, p = 0.064 and HR = 0.74, 95% CI 0.55–0.99, p = 0.042, respectively).
Conclusions
Our study showed that duration on ADT for mHSPC was significantly associated with survival in mCRPC undergoing ARSI. These findings suggest a possible connection between initial management of prostate tumour and a better prognostication in mCRPC. Prospective trials are warranted.
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Data availability
The anonymized datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Funding
This research was supported by ‘PRA-HE (Progetti di Ricerca di Ateneo propeudetici all’accesso ai finanziamenti del programma Horizon Europe) 2021’ to VC and ‘PNRR - M4C2-I1.3 Project PE_00000019 “HEAL ITALIA”, ‘5 per mille 2018-2019 LILT Investigator Grant’, ‘Ministry of University and Research (PRIN – PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE – Università degli Studi di Foggia – CUP D53D23014290006) and ‘Iniziativa regionale “RIPARTI: assegni di RIcerca per riPARTire con le Imprese” – CUP D74C22000040002’ to ML.
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VC conceptualized, designed and wrote the study. VC, PDT, RA, GB, CL, GS, GG, MG, VEC, LC, EZ, LG, FM, UF, PR, GF, FS, DS, GP, OC, and GC involved in acquisition of data. VC and AR analyzed and interpreted the data. ML and UDG revised the manuscript.
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VC has served as a consultant/advisory board member for Janssen, Astellas, Merck, AstraZeneca, Amgen, EISAI, Recordati, Novartis, Ipsen and Bayer and has received speaker honoraria or travel support from Astellas, Janssen, Ipsen, Bayer, Gilead and Bristol Myers Squibb. PR served as an advisory board for MSD and AstraZeneca Italy. FM has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer. GF served as an advisory board member for Astellas, Janssen, Pfizer, Bayer, MSD, Merck and received travel accommodation from Astellas, Janssen, Bayer. GP served as a consultant and/or a speaker for Bayer, BMS, Novartis, Amgen, Pfizer, Janssen, Ipsen, Boehringer. OC served as an advisory/board member of AAA, AstraZeneca, Astellas, Bayer, Janssen, Ipsen, MSD, Pfizer, and has received speaker honoraria from Ipsen, MSD, AstraZeneca, Astellas, Janssen. UDG served as an advisory/board member of Astellas, Bayer, BMS, IPSEN, Janssen, Merck, Pfizer, Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi and travel/accommodations/expenses from BMS, IPSEN, Janssen, Pfizer. No potential conflicts of interest were disclosed by the other authors.
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Conteduca, V., Di Tullio, P., Allamprese, R. et al. Initial management approach for localized/locally advanced disease is critical to guide metastatic castration-resistant prostate cancer care. Prostate Cancer Prostatic Dis (2024). https://doi.org/10.1038/s41391-024-00800-8
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DOI: https://doi.org/10.1038/s41391-024-00800-8
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