The Natural History and Outcome Predictors of Metastatic Castration-resistant Prostate Cancer

Robert J van Soest, Jason A Efstathiou, Cora N Sternberg, Bertand Tombal
European Urology Focus 2016, 2 (5): 480-487

CONTEXT: Biomarkers for the treatment of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed by clinicians to facilitate treatment decisions.

OBJECTIVE: To review current prognostic and predictive biomarkers in mCRPC.

EVIDENCE ACQUISITION: We performed a nonsystematic review of the literature from 2004 to August 2016 by searching in Medline. Cross-matching references were used to search for additional articles. We reviewed clinical research and review articles written in the English language.

EVIDENCE SYNTHESIS: Nomograms of prognostic factors (eg, albumin, lactate dehydrogenase) enable clinicians to estimate the prognosis of men with mCRPC. These prognostic tools may aid with when to trigger treatment, therapeutic monitoring, and follow-up. However, validated predictive biomarkers in mCRPC are still lacking. Androgen receptor (AR) splice variants (ie, AR-V7), gene fusions, and point mutations determined using liquid biopsies such as circulating tumor cells (CTCs) or cell-free DNA (cfDNA) are promising biomarkers that are the subject of ongoing research. Patient biomarkers (eg, neutrophil-to-lymphocyte ratio) are readily available and come with no extra cost but need further validation before their implementation in clinical practice.

CONCLUSIONS: Determination of AR-V7 in CTCs is a big step towards a more personalized treatment approach in mCRPC. Genomic characterization of liquid biopsies such as CTCs, cfDNA, and circulating RNA are noninvasive tools to further personalize treatment in prostate cancer. Clinical parameters are readily available, but are derived from retrospective studies and should be interpreted with care. Only by conducting biomarker-driven studies, rather than large one-size-fits-all trials, will we be able to improve prostate cancer treatment.

PATIENT SUMMARY: Several biomarkers are currently under investigation that may predict which patients will respond to specific therapies in the future of metastatic castration-resistant prostate cancer treatment.

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