Androgen deprivation therapy ± new antihormonal therapy for the treatment of metastatic hormone-sensitive prostate cancer

Background: From 1941 to 2014, metastatic hormone-sensitive prostate cancer (mHSPC) was solely treated by surgery or medical castration (androgen deprivation therapy [ADT]). In 2014, the addition of docetaxel chemotherapy (CTX) was shown to significantly improve overall survival. However, CTX is not ideal for all patients. Some are too old, too sick, or oppose to treatment with CTX. Therefore, alternatives with low toxicity and equal efficacy were explored. Abiraterone (Abi), apalutamide (Apa), and enzalutamide (Enza) are new antihormonal therapies (NHT) which meet these requirements. Objectives: To review the role of NHTs + ADT in mHSPC. Materials and methods: Prerequisites and challenges are summarized and key data on combination therapy with NHTs + ADT in mHSPC are reviewed. Results: Treatment of mHSPC with Abi, Apa, or Enza represents a big step forward. Especially for patients who do not qualify for CTX or oppose CTX, NHTs are a valid alternative. The use of Abi is more challenging than the use of Apa and Enza due to more complex conditions that need to be fulfilled for its use. Thus, the time for the patient in the mHSPC stage will be longer with more intensive androgen deprivation, which may lead to increased risk of cardiovascular disease and osteoporosis. When choosing a treatment with NHTs in this setting, possible follow-up treatment needs to be considered. Conclusions: Treatment of mHSPC using NHTs + ADT is an important new standard. Almost every patient can be treated with one of the NHTs with relatively low risk of toxicity. Therefore, these treatments are widely used. In the future, the addition of new therapeutics could further strengthen the relevance of NHTs in the mHSPC setting.