Changing face of metastatic prostate cancer: the law of diminishing returns holds true.

PURPOSE OF REVIEW: Prostate cancer presents with a multitude of faces. It ranges from localized cancers staying quiescent for many years during active surveillance to the raging diffuse liver metastases causing terminal disease. The incidence of metastatic disease is increasing. This review will highlight some of the recent developments as well as ongoing challenges of managing advanced prostate cancer.

RECENT FINDINGS: Significant strides are being made in managing metastatic prostate cancer. With the evolution of multiple new therapies, now the optimal use of these therapies and their proper sequencing is being addressed. Research is ongoing for mapping out pathways of resistance to therapies and for discovering new targets. Genomic alterations and abnormalities in circulating tumor DNA are being detected and will hopefully lead us more toward biomarker based therapies. The next era in oncology belongs to immune therapy. However, in prostate cancer the immune checkpoint inhibitors have shown modest responses and a phase III trial of radiation therapy ± ipilimumab revealed no benefit. Efforts are ongoing with combination trials of enzalutamide and atezolizumab or pembrolizumab. PARP inhibitors are gradually being established for therapeutic purposes, with olaparib achieving breakthrough status for prostate cancer patients with BRCA1 and 2 and ATM mutations.

SUMMARY: The future will bring an era of personalized medicine in advanced prostate cancer as well as optimization and more strategic sequencing of existing therapies.