After almost 20 years of negative trials of novel therapies for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), two androgen receptor antagonists have shown favourable outcomes in phase III trials involving patients with high-risk nmCRPC. Herein, the history of nmCRPC and clinical trials in this disease setting are discussed and a perspective on molecular imaging and clinical management of nmCRPC is offered.
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Scher, H. I. & Heller, G. Clinical states in prostate cancer: toward a dynamic model of disease progression. Urology 55, 323–327 (2000).
Smith, M. R. et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J. Clin. Oncol. 23, 2918–2925 (2005).
Smith, M. R. et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomized, placebo-controlled trial. Lancet 379, 39–46 (2012).
Smith, M. R. et al. Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J. Clin. Oncol. 31, 3800–3806 (2013).
Nelson, J. B. et al. Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer 113, 2478–2487 (2008).
Nelson, J. B. et al. Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone. Cancer 118, 5709–5718 (2012).
Small, E. J. et al. SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) [abstract]. J. Clin. Oncol. 36 (Suppl. 6), 161 (2018).
Hussain, M. et al. PROSPER: a phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC) [abstract]. J. Clin. Oncol. 36 (Suppl. 6), 3 (2018).
Smith, M. R. et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N. Engl. J. Med. 378, 1408–1418 (2018).
Xie, W. et al. Metastasis-free survival is a strong surrogate of overall survival in localized prostate cancer. J. Clin. Oncol. 35, 3097–3104 (2017).
Yu, E. Y. et al. Detection of previously unidentified metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer. J. Urol. 188, 103–109 (2012).
Terada, N. et al. Exploring the optimal sequence of abiraterone and enzalutamide in patients with chemotherapy naïve castration-resistant prostate cancer: the Kyoto-Baltimore collaboration. Int. J. Urol. 24, 441–448 (2017).
C.S.H. has served on advisory boards and/or steering committees for Astellas, Bayer, Blue Earth Diagnostics, Clovis Oncology, Ferring, Janssen, Myriad, and Tolmar, has received Institutional research funding from Aptevo, Aragon, Astellas, AstraZeneca, Bayer, Hoffman LaRoche, Janssen, Medivation, and Pfizer, and declares that her spouse is a co-founder of, and has a leadership role at, CTI Biopharma.
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Higano, C.S. Does nonmetastatic castration-resistant prostate cancer still exist?. Nat Rev Clin Oncol 15, 350–351 (2018) doi:10.1038/s41571-018-0025-z
Nature Reviews Clinical Oncology (2019)