Molecular Profiling of Prostate Cancer

Prostate cancer is the second most common cancer in men worldwide, accounting for 15% (1.1 million) of the total new male cancer cases and 6.6% (307,000) of the total cancer deaths in men in 2012 (GLOBOCAN 2012 v1.1). In the U.S., 164,690 new cases and 29,430 deaths are estimated for 2018 (ACS 2018). In the U.S., approximately 92% of prostate cancers are discovered at local or regional stage; the 5-year relative survival rates for these cancers is ~100% (ACS 2016). The 5-year relative survival rates for all stages combined is 99%, with 10- and 15- year survival rates for all stages being 98% and 95%, respectively (ACS 2016). On the other hand, the median overall survival of patients with metastatic castration resistant prostate cancer (mCRPC) is between 2-3 years (WHO 2015; Heidenreich et al. 2013; Omlin et al. 2013), although more recent studies suggest an that newer treatment regimens may extend overall survival of these patients beyond this estimate (Afshar et al. 2015; Heidenreich et al. 2013).

Traditionally, biomarkers like tumor stage, prostate-specific antigen (PSA) levels, and histopathological grading have been used to guide clinical decisions (Otero et al. 2014; Saini 2016). In recent years, several diagnostic and prognostic molecular biomarker tests have been developed for clinically localized disease (Leapman et al. 2016; Saini 2016). Additionally number of novel biomarkers are being investigated for mCRPC that have potential clinical validity as predictive and/or prognostic biomarkers, including circulating tumor cells, various genetic alterations, mRNA splice variants, microRNAs, and exosomes (Antonarakis et al. 2016; Bryce and Antonarakis 2016; Leapman et al. 2016; Rodrigues et al. 2014; Saini 2016; Seisen et al. 2016). These new molecular biomarkers need further study to establish their clinical utility in predicting patient response to systemic therapies.

Traditional treatment regimens for metastatic disease focus on androgen deprivation therapy, through surgical or pharmacological castration; this approach has been the primary treatment for prostate cancer for nearly 70 years and is successful at inducing tumor regressions in nearly all patients (Huggins and Hodges 1941; Huggins et al. 1941; NCCN 2016). However given long enough, patients will progress on these therapies to metastatic castration-resistant prostate cancer (mCRPC), an ultimately lethal disease that is no longer sensitive to first-line androgen deprivation therapies (Tan et al. 2015; Watson et al. 2015). Despite significant advances in the treatment of patients with mCRPC with six systemic therapies approved in the U.S. (i.e., abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, sipeuleucel-T, radium-223), these therapies are not curative and novel targeted therapies and other treatment strategies are needed.

Contributors: Himisha Beltran, M.D.

Suggested Citation: Beltran, H. 2018. Molecular Profiling of Prostate Cancer. My Cancer Genome (Updated March 16).

Last Updated: March 16, 2018

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