Re: Reevaluating PSA Testing Rates in the PLCO Trial

Abstract

available at http://www.ncbi.nlm.nih.gov/pubmed/27262168 Editorial Comment: The role of circulating tumor cells (CTCs) in predicting prostate cancer stage and prognosis has been studied literally since I was a third year resident in the early 1990s. Initial studies were neither conclusive nor provocative, and the use of CTCs really never caught on as a standard modality. Through the years the science has improved in many ways. CTCs can be more readily and reliably identified. CTCs can be accurately quantified through automated methods. And now, most importantly, CTCs can be well characterized at the cell surface and the intracellular protein level. In this study the authors use methods of characterizing CTCs as a means of determining the presence of an androgen receptor mutation, the AR-V7 splice variant. This mutation has previously been demonstrated as a potential mechanism of enzalutamide resistance and is known to be present in a significant proportion of men with progression on enzalutamide therapy. The authors were able to determine the presence of nuclear AR-V7 protein in CTCs in a series of men undergoing therapy for castration resistant prostate cancer (CRPC). Men with expression of nuclear AR-V7 protein were more commonly found among those who had previously been treated with 1 or more therapies for CRPC, and the splice variant was rare in those not previously treated. Men with nuclear AR-V7 protein expression were more likely to do poorly on AR directed therapies compared to those without AR-V7 protein expression, and they were more likely to fare better with a taxane than an AR targeting agent. The use of these elegant molecular techniques may allow direction in the often unclear practice of sequencing therapeutic agents in men with CRPC. Samir S. Taneja, MD Suggested Reading Mejean A, Vona G, Nalpas B et al: Detection of circulating prostate derived cells in patients with prostate adenocarcinoma is an independent risk factor for tumor recurrence. J Urol 2000; 163: 2022. Okegawa T, Nutahara K and Higashihara E: Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol 2009; 181: 1091. Small AC, Gong Y, Oh WK et al: The emerging role of circulating tumor cell detection in genitourinary cancer. J Urol 2012; 188: 21. Re: Addition of Docetaxel, Zoledronic Acid, or Both to First-Line Long-Term Hormone Therapy in Prostate Cancer (STAMPEDE): Survival Results from an Adaptive, Multiarm, Multistage, Platform Randomised Controlled Trial N. D. James, M. R. Sydes, N. W. Clarke, M. D. Mason, D. P. Dearnaley, M. R. Spears, A. W. Ritchie, C. C. Parker, J. M. Russell, G. Attard, J. de Bono, W. Cross, R. J. Jones, G. Thalmann, C. Amos, D. Matheson, R. Millman, M. Alzouebi, S. Beesley, A. J. Birtle, S. Brock, R. Cathomas, P. Chakraborti, S. Chowdhury, A. Cook, T. Elliott, J. Gale, S. Gibbs, J. D. Graham, J. Hetherington, R. Hughes, R. Laing, F. McKinna, D. B. McLaren, J. M. O’Sullivan, O. Parikh, C. Peedell, A. Protheroe, A. J. Robinson, N. Srihari, R. Srinivasan, J. Staffurth, S. Sundar, S. Tolan, D. Tsang, J. Wagstaff and M. K. Parmar