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Initial management approach for localized/locally advanced disease is critical to guide metastatic castration-resistant prostate cancer care

Prostate Cancer and Prostatic Diseases (2024)Cite this article

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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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Fig. 1: Overall survival and progression-free survival from initiation of ARSI therapy in the primary progressive population by risk category and ADT duration.
Fig. 2: Overall survival and progression-free survival from initiation of ARSI therapy in de novo metastatic population by time to CRPC.

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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.

Author information

Author notes

  1. These authors jointly supervised this work: Matteo Landriscina, Ugo De Giorgi.

Authors and Affiliations

  1. Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, 71122, Foggia, Italy

    Vincenza Conteduca, Piergiorgio Di Tullio, Rossana Allamprese, Giuseppina Bruno, Guido Giordano, Marianna Garofoli, Ugo Falagario, Francesca Sanguedolce, Giuseppe Carrieri & Matteo Landriscina

  2. Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCSCROB), Rionero in Vulture, Italy

    Rossana Allamprese

  3. Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy

    Cristian Lolli, Giuseppe Schepisi & Ugo De Giorgi

  4. National Institute for the Analysis of Public Policy—INAPP, 00198, Rome, Italy

    Aldo Rosano

  5. Ospedale “Sacro Cuore di Gesù”, Gallipoli, Italy

    Vincenzo Emanuele Chiuri

  6. Medical Oncology Department, National Cancer Institute, Aviano, Italy

    Lucia Fratino

  7. IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Elisa Zanardi & Giuseppe Fornarini

  8. Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    Luca Galli

  9. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Francesco Massari

  10. Department of Urology, University of Foggia, Foggia, Italy

    Ugo Falagario

  11. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Ugo Falagario

  12. Department of Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy

    Pasquale Rescigno

  13. Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK

    Pasquale Rescigno

  14. UOC Oncologia A, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy

    Daniele Santini

  15. Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Giuseppe Procopio

  16. Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy

    Orazio Caffo

Authors
  1. Vincenza Conteduca
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  2. Piergiorgio Di Tullio
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Contributions

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.

Corresponding author

Correspondence to Vincenza Conteduca.

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Competing interests

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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