Urological Survey Urological Oncology : Prostate Cancer Re : Validation of a Cell-Cycle Progression Gene Panel to Improve Risk Stratification in a Contemporary Prostatectomy Cohort

available at http://jurology.com/ Editorial Comment: There has been a strong interest in defining genetic markers that might predict disease outcome in men with early stage prostate cancer to better select those in need of treatment. Recently a number of gene panels have been reported to allow prediction of disease recurrence and progression. In this study one such panel, consisting of 33 cell cycle associated genes, was validated in a contemporary cohort of prostatectomy cases. The panel expression, called cell cycle progression score, was able to further stratify men within low and intermediate risk cohorts, as measured by Cancer of the Prostate Risk Assessment Post-Surgical score, in terms of predicting biochemical relapse. It will be important to determine if this re-segregation of risk is clinically meaningful in counseling patients. It is unclear whether a man with a 10% predicted risk of recurrence would be greatly influenced by the information that his risk is actually 2% or 20%, and the impact may vary with the individual patient. Nonetheless, the findings are particularly provocative if they translate into more reliable predictive outcomes for men considering surveillance based on biopsy alone. The issue of tumor heterogeneity and sampling efficiency (acknowledged in part by the authors) remains the most critical question. In this study tumor was sampled from the dominant tumor site, presumably defined by the largest focus. It is not intuitive that tumor genetics could be predicted accurately by random sampling of cancer at sites potentially distant from the dominant, or most aggressive, tumor component. Future studies of heterogeneity will be essential in determining the clinical usefulness in practice. Samir S. Taneja, M.D. Re: Transperineal Template-Guided Saturation Biopsy Using a Modified Technique: Outcome of 270 Cases Requiring Repeat Prostate Biopsy K. Ekwueme, H. Simpson, H. Zakhour and N. J. Parr Department of Urology, Wirral University Teaching Hospital, Wirral, United Kingdom BJU Int 2013; 111: E365eE373. Abstract available at http://jurology.com/available at http://jurology.com/ Editorial Comment: The approach to repeat prostate biopsy in clinical practice represents a major challenge for urologists in the future. The desire to identify missed cancers has to be balanced against the risk of small indolent cancers through over sampling. In this study the authors describe a modified technique of transperineal template biopsy in men requiring repeat biopsy following an 0022-5347/13/1904-1245/0 THE JOURNAL OF UROLOGY © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. http://dx.doi. org/10.1016/j.juro. 2013.06. 101 Vol. 190, 1245-1254, October 2013 Printed in U.S.A. www.jurology.com j 1245 1246 PROSTATE CANCER initial negative result in which the periurethral region is avoided to reduce morbidity. In doing so, they attempt to decrease false-negative biopsies, which secondarily might reduce the number of repeat biopsies performed. A high cancer detection rate was noted, and interestingly a number of posterior, presumably peripheral zone cancers were identified. Additionally several high grade cancers were detected. While the reported morbidity is low, and the detection rate is high, I worry that an approach of increased sampling will ultimately result in an increase in morbidity and cost. Ongoing attempts to decrease false-negative biopsies through image guided biopsy may offer an opportunity to reduce sampling error through localization rather than excessive sampling. Samir S. Taneja, M.D. Suggested Reading Igel TC, Knight MK, Young PR et al: Systematic transperineal ultrasound guided template biopsy of the prostate in patients at high risk. J Urol 2001; 165: 1575. Huo AS, Hossack T, Symons JL et al: Accuracy of primary systematic template guided transperineal biopsy of the prostate for locating prostate cancer: a comparison with radical prostatectomy specimens. J Urol 2012; 187: 2044. Re: Use of Testosterone Replacement Therapy in the United States and its Effect on Subsequent Prostate Cancer Outcomes A. L. Kaplan and J. C. Hu Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California Urology 2013; Epub ahead of print. Abstract available at http://jurology.com/available at http://jurology.com/ Editorial Comment: The authors compared men receiving testosterone replacement to those not receiving testosterone replacement at prostate cancer diagnosis and found low rates of testosterone replacement, no worsening of pathology or clinical outcome, and improved cancer specific survival among men undergoing frequent prostate specific antigen testing. The conclusions of this study should be considered with caution. It has previously been suggested that men who are hypogonadal at prostate cancer diagnosis have higher grade, more advanced stage disease and worse clinical outcomes than men who are eugonadal at diagnosis. The influence of testosterone replacement in these men with occult high grade cancers cannot really be ascertained from this study. Several points should be considered. It is unknown how many men with hypogonadism underwent biopsy before consideration of testosterone supplementation and, therefore, were excluded from testosterone replacement. Removal of cases of high risk cancer before testosterone replacement shifts the population to lower risk disease. It is also unclear from the study how long men received testosterone before diagnosis and how many of these men had a negative biopsy before initiation of testosterone. Previous negative biopsy shifts a population to lower volume disease at detection. In clinical practice men on testosterone supplementation are monitored frequently for prostate cancer and biopsied at increase (often slight). Earlier biopsy shifts a population to lower disease volume at detection. As such, improved cancer outcomes and favorable disease pathology likely represent a selection bias in this group, partly because of previous biopsy and partly because of lower biopsy threshold. I do not believe the article offers sufficient information to influence clinical practice. Samir S. Taneja, M.D.