Optimal Treatment Sequence for Metastatic Castration-resistant Prostate Cancer

Context Unprecedented development of therapeutics for prostate cancer in recent years has left clinicians with the challenge of adequately sequencing therapeutic agents to optimise patient benefit. No clear guidelines exist on optimal treatment sequences. Objective To summarise the evidence on first-line activity, cross-resistance, and potential combinations of agents approved for metastatic castration-resistant prostate cancer (mCRPC). Evidence acquisition A nonsystematic literature search of articles on agent sequencing in mCRPC in PubMed and relevant cancer conferences up to June 2016 was performed. Evidence synthesis No definitive evidence on the optimal mCRPC treatment sequence exists. Hormonal agents are preferred for first-line treatment on the basis of favourable toxicity, but no evidence of superiority over chemotherapy exists. Evidence suggests significant cross-resistance between agents in first- and second-line settings. The impact of prior chemotherapy in metastatic hormone-sensitive disease is unknown. No combinations have proven benefit to date. Molecular biomarker assessment in liquid biopsies may aid selection of treatment in the near future. Conclusions It is unlikely that a single sequence will be adequate for all mCRPC patients. An individualised strategy that assesses the biological mechanisms of the disease and monitors molecular drivers of progression and resistance to treatment is required to maximise benefit for each patient and bring us closer to the goal of best care. Patient summary In this review we summarise evidence on the optimal sequence of anticancer drugs for metastatic castration-resistant prostate cancer. No agent has proven superior to another as front-line treatment, and the exact impact of prior treatments on drug efficacy is unknown. Better biomarkers for treatment selection and evaluation of response to treatment will be needed to personalise the optimal sequence for each individual patient.