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

Vincenza Conteduca; Piergiorgio Di Tullio; Rossana Allamprese; Giuseppina Bruno; Cristian Lolli; Giuseppe Schepisi; Aldo Rosano; Guido Giordano; Marianna Garofoli; Vincenzo Emanuele Chiuri; Lucia Fratino; Elisa Zanardi; Luca Galli; Francesco Massari; Ugo Falagario; Pasquale Rescigno; Giuseppe Fornarini; Francesca Sanguedolce; Daniele Santini; Giuseppe Procopio; Orazio Caffo; Giuseppe Carrieri; Matteo Landriscina; Ugo De Giorgi

doi:10.1038/s41391-024-00800-8

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

Prostate Cancer Prostatic Dis. 2024 Feb 12. doi: 10.1038/s41391-024-00800-8. Online ahead of print.

Authors

Vincenza Conteduca¹, Piergiorgio Di Tullio², Rossana Allamprese^{2

3}, Giuseppina Bruno², Cristian Lolli⁴, Giuseppe Schepisi⁴, Aldo Rosano⁵, Guido Giordano², Marianna Garofoli², Vincenzo Emanuele Chiuri⁶, Lucia Fratino⁷, Elisa Zanardi⁸, Luca Galli⁹, Francesco Massari¹⁰, Ugo Falagario^{2

11

12}, Pasquale Rescigno^{13

14}, Giuseppe Fornarini⁸, Francesca Sanguedolce², Daniele Santini¹⁵, Giuseppe Procopio¹⁶, Orazio Caffo¹⁷, Giuseppe Carrieri², Matteo Landriscina², Ugo De Giorgi⁴

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@unifg.it.
² Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, 71122, Foggia, Italy.
³ Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCSCROB), Rionero in Vulture, Italy.
⁴ Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
⁵ National Institute for the Analysis of Public Policy-INAPP, 00198, Rome, Italy.
⁶ Ospedale "Sacro Cuore di Gesù", Gallipoli, Italy.
⁷ Medical Oncology Department, National Cancer Institute, Aviano, Italy.
⁸ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
⁹ Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
¹⁰ Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
¹¹ Department of Urology, University of Foggia, Foggia, Italy.
¹² Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
¹³ Department of Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.
¹⁴ Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
¹⁵ UOC Oncologia A, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
¹⁶ Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
¹⁷ Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy.

PMID: 38347113
DOI: 10.1038/s41391-024-00800-8

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.