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Review
. 2022 Sep 29:14:339-350.
doi: 10.2147/RRU.S360444. eCollection 2022.

Treatment Landscape for Patients with Castration-Resistant Prostate Cancer: Patient Selection and Unmet Clinical Needs

Fabio Turco  1   2 , Silke Gillessen  1   3 , Richard Cathomas  4 , Consuelo Buttigliero  2 , Ursula Maria Vogl  1
Affiliations
Review

Treatment Landscape for Patients with Castration-Resistant Prostate Cancer: Patient Selection and Unmet Clinical Needs

Fabio Turco et al. Res Rep Urol. .

Abstract

Metastatic castration resistant prostate cancer (CRPC) is an inevitably fatal disease. However, in recent years, several treatments have been shown to improve the outcome of CRPC patients both in the non-metastatic (nmCRPC) as well as the metastatic setting (mCRPC). In nmCRPC patients with a PSA doubling time <10 months, the addition of enzalutamide, apalutamide and darolutamide to androgen deprivation therapy (ADT) compared to ADT alone resulted in improved metastases free (MFS) and overall survival (OS). For mCRPC patients, several treatment options have been shown to be effective: two taxane based chemotherapies (docetaxel and cabazitaxel), two androgen-receptor pathway inhibitors (ARPI) (abiraterone and enzalutamide), two radiopharmaceutical agents (radium 223 and 177Lutetium-PSMA-617), one immunotherapy treatment (sipuleucel-T) and two poly ADP-ribose polymerase (PARP) inhibitors (olaparib and rucaparib). Pembrolizumab is US Food and Drug Administration (FDA) approved in all MSI high solid tumors, although a very small proportion of prostate cancer patients harboring this characteristic will benefit. Despite having a broad variety of treatments available, there are still several unmet clinical needs for CRPC. The objective of this review was to describe the therapeutic landscape in CRPC patients, to identify criteria for selecting patients for specific treatments currently available, and to address the current challenges in this setting.

Keywords: castration resistant prostate cancer; metastatic castration resistant prostate cancer; non-metastatic castration resistant prostate cancer; prostate cancer.

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Conflict of interest statement

Fabio Turco: travel grant: Bayer. Silke Gillessen: received personal honoraria for participation in advisory boards for Sanofi, Orion, Roche, Amgen, AstraZeneca, Novartis, Myriad Genetics, MSD; other honoraria from RSI (Televisione Svizzera Italiana); invited speaker for ESMO, Swiss group for Clinical Cancer Research (SAKK), Swiss Academy of Multidisciplinary oncology (SAMO), Orikata academy research group, China Anti-Cancer Association Genitourinary Oncology Committee (CACA-GU), S. Grasso Consulting, Beijing United Family Hospital and Clinics, Deso St Gallen; Speaker’s bureau for Janssen Cilag; travel grant from ProteoMEdiX; institutional honoraria for advisory boards for Bayer, Janssen Cilag, Roche, AAA International including Independent Data Monitoring Committee and IDMC; Steering Committee member for Amgen, Menarini Silicon Biosystems, Astellas Pharma, Tolero Pharmaceuticals, MSD, Pfizer, Telixpharma, BMS, and Orion; fees for the institute for faculty activity ASCO GU from WedMed-Medscape; patent royalties and other intellectual property for a research method for biomarker WO2009138392. Richard Cathomas: Advisory board (institutional): Astellas, Astra Zeneca, BMS, Merck, MSD, Pfizer, Ipsen, Roche, Debiopharm, Novartis, Bayer, Janssen (personal), Sanofi. Honoraria (institutional): Janssen, Astellas. Ursula Maria Vogl: Honorary for Advisory Board and Speaker fee (institutional): Pfizer, Bayer, MSD, BMS, Eisei, Astellas, Janssen, Sanofi, Novartis AAA, Merck, Ipsen; Honorary for Speaker fee, travel grant (private): SAMO, Inselspital Bern, Kantonsspital St. Gallen, Kantonsspital Chur, Healthbook, Merck, Ipsen. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Timeline of treatments for mCRPC (year of reported positive pivotal trial). 1,2Tannock, IF et al. N Engl J Med 2004; 3De Bono, J et al. Lancet 2010, 4Oudard, S et al. J Clin Oncol 2017, 5Kantoff, P.W. et al. N Engl J Med. 2010; 6De Bono, J et al. N Engl J Med. 2011, 7Ryan, CJ et al. N Engl J Med. 2013, 8Scher, HI et al. N Engl J Med 2012; 9Beer, TM et al. N Engl J Med 2014, 10Parker, C et al. N Engl J Med. 2013, 11Nilsson S et al. Ann Oncol. 2016; 12De Bono, J et al. N Engl J Med 2020;13Sartor O et al. N Engl J Med. 2021. *Approval EMA withdrawn, not available in Europe; +symptomatic, bone only, LN<3cm, visceral mets. excluded; approval §EMA: BRCA1,2 FDA: HRD panel PROfound, Rucaparib (FDA only); **FDA only approval, not EMA.
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References

    1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660 - DOI - PubMed
    1. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293–297. - PubMed
    1. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737–746. doi:10.1056/NEJMoa1503747 - DOI - PMC - PubMed
    1. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163–1177. doi:10.1016/S0140-6736(15)01037-5 - DOI - PMC - PubMed
    1. Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352–360. doi:10.1056/NEJMoa1704174 - DOI - PubMed