Charting Recent Progress and Challenges in Metastatic Castration-resistant Prostate Cancer: Is There an Optimal Treatment Sequence?

CONTEXT: Recent developments in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have led to uncertainty about the optimal sequence of agents.

OBJECTIVE: To review and assess treatment options and sequence in patients with mCRPC.

EVIDENCE ACQUISITION: To identify data on the optimal use of approved treatments, we searched PubMed for studies on the use of recently approved agents for men with mCRPC published before March 2015. Phase 3 and other key studies were included in the review of efficacy and safety. In this review, we offer our critical interpretation of potential treatment sequences for drug use in the light of our clinical experience.

EVIDENCE SYNTHESIS: Since 2004, the treatment landscape for mCRPC has changed dramatically following the approval of docetaxel, abiraterone acetate, enzalutamide, cabazitaxel, denosumab, and radium-223 chloride. To date, only small-scale studies have been undertaken that provide evidence on the sequencing of these treatments. Ideally, randomised, prospective studies would evaluate different sequence options thoroughly so that physicians could make evidence-based decisions, but the number of new agents makes this impractical. When deciding which treatment to prescribe, physicians will need to use the available evidence combined with their own clinical judgement. The potential for cross-resistance between taxanes and hormonal therapies and the possibility that patients might not be suitable for aggressive therapies in later lines should be taken into account. Prevention of complications associated with bone metastases should also be a key consideration because of the major impact these events have on quality of life and healthcare costs.

CONCLUSIONS: The recent approval of numerous new agents has resulted in considerable improvements in outcomes for patients with mCRPC. Further studies determining the optimal treatment algorithm, in addition to open discussion of best practice among physicians, are required to ensure patients obtain the maximum possible benefit from their treatment.

PATIENT SUMMARY: In recent years a large number of new treatment options have been approved for use in men with prostate cancer. In the absence of clinical trials assessing the use of one option versus another in specific patient groups, it is important to review the currently published evidence to try to understand patients receive the best treatment options in the correct order.