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Metastatic hormone-sensitive prostate cancer: A Systematic Review of the Value of Current Therapies

Wafaa Kaikani

PROSTATE cancer (PC) is the second most frequent cancer in males. Based on GLOBOCAN 2018 estimates, 1,356,176 new cases of prostate cancer and a mortality of 378,553 are expected in 20201. Despite an overall 5-year survival rate of 98.2%, mHSPC has a dismal 30% 5-year survival rate2. Metastatic hormone-sensitive prostate cancer (mHSPC) is the disease space whereby men have metastatic prostate cancer and have never received (ie. are sensitive to) androgen deprivation therapy (ADT). mHSPC previously constituted ~30% of prostate cancer cases , however, from 2004-2012 secondary to PSA testing, the estimate was ~5% of cases in USA3. Many experts in the field suggest that with decreased PSA screening over the last few years, as a result of the United States Preventative Services Task Force (USPSTF) Grade D recommendation for PSA screening (subsequently upgraded to C 4), that these estimates are likely to once again increase 5. At diagnosis, 77% of prostate cancer cases are localized; in 13%, the cancer has spread to regional lymph nodes, and 6% have distant metastasis. The 5-year relative survival rate for localized and regional prostate cancer is 100%, compared with 30.5% for metastatic cases. 2Conventional treatment of mHSPC has been ADT since the land- mark discovery by Huggins and Hodges in 1941 demonstrating the hormonal sensitivity of PC. Since 2015; we have seen several landmark trials published that have added therapies to ADT for these men, favorably impacting overall survival (OS). Men are now faced with decisions of androgen-deprivation therapy alone or combinations with either docetaxel, abiraterone, enzalutamide, or apalutamide, and there are now additional complex decisions around triple combination or sequential therapy with induction androgen-deprivation therapy/docetaxel plus a potent androgen-re- ceptor inhibitor or whether single-agent chemotherapy or androgen-receptor inhibitor use with androgen-deprivation therapy is sufficient. These decisions are presently based on costs, availability and approvals, disease risk/volume, patient age and comorbidity, and of course shared decision-making. This article will discuss the effect of docetaxel and inhibitors of androgen signaling developed in the past 5 years among men with mHSPC and review the subsequent literature following reporting of these trials.