Cytoreductive treatment strategies for de novo metastatic prostate cancer

In the past decade, a revolution in the treatment of metastatic prostate cancer has occurred with the advent of novel hormonal agents and life-prolonging chemotherapy regimens in combination with standard androgen-deprivation therapy. Notwithstanding, the use of systemic therapy alone can result in a castrate-resistant state; therefore, increasing focus is being placed on the additional survival benefits that could potentially be achieved with local cytoreductive and/or metastasis-directed therapies. Local treatment of the primary tumour with the established modalities of radiotherapy and radical prostatectomy has been explored in this context, and the use of novel minimally invasive ablative therapies has been proposed. In addition, evidence of the potential clinical benefits of metastasis-directed therapy with ionizing radiation (primarily stereotactic ablative radiotherapy) is accumulating. Herein, we summarize the pathobiological rationale for local cytoreduction and the potentially systemic immunological responses to radiotherapy and ablative therapies in patients with metastatic prostate cancer. We also discuss the current evidence base for a cytoreductive strategy, including metastasis-directed therapy, in the current era of sequential multimodal therapy incorporating novel treatments. Finally, we outline further research questions relating to this complex and evolving treatment landscape. Systemic hormone therapies and chemotherapy are the cornerstones of treatment for patients with de novo metastatic prostate cancer, with a currently limited role for local treatments. Herein, the authors outline the pathobiological and immunological rationale for local cytoreductive treatment of the primary tumour and/or metastases in patients with this disease. They also review the preclinical and clinical evidence for the use of radical prostatectomy, prostate radiotherapy, minimally invasive ablative therapies, and metastasis-directed therapy (predominantly with stereotactic ablative radiotherapy) in this population. Key points The treatment of de novo, synchronous castration-sensitive metastatic prostate cancer has undergone a revolution with the advent of novel hormone therapies and life-prolonging chemotherapy for use in combination with androgen-deprivation therapy. Men with low-burden metastatic (oligometastatic) prostate cancer can have localized disease control and substantial delays in disease progression with local cytoreductive treatment of the primar