Thwarting high-risk prostate cancer: The right treatments for the right patients

EUROPEAN UROLOGY 61 (2012) 1107–1109 available at www.sciencedirect.com journal homepage: www.europeanurology.com Platinum Priority – Editorial Referring to the article published on pp. 1096–1106 of this issue Thwarting High-risk Prostate Cancer: The Right Treatments for the Right Patients Matthew R. Cooperberg * Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, Box 1695, 1600 Divisadero St, A-624, San Francisco, CA 94143-1695, USA Age-adjusted prostate cancer mortality rates have fallen roughly 40% in the United States since the advent of prostate- specific antigen (PSA)–based screening two decades ago [1]. Notwithstanding widely acknowledged problems with over- treatment of low-risk disease and controversies surrounding optimal screening strategies, the preponderance of evidence suggests that this favorable trend in mortality rates can be attributed in large part to some combination of earlier detection and better management of high-risk prostate cancer. In fact, many of the challenges going forward in prostate cancer research and clinical care might be summa- rized in the quandary of how to continue driving mortality rates downward while minimizing both overtreatment and the collateral impacts of treatments when they are required. Greater acceptance of active surveillance and ongoing technical refinements will continue to support the latter half of this equation; the former will depend on better management—identification and treatment—of high-risk disease. The timely and comprehensive review by Bastian et al. [2] covers many important issues within the broad topic of high-risk prostate cancer, the majority of which boil down to two critical questions: How should high-risk prostate cancer be defined? And by what approach should it best be managed initially? The review impartially summarizes many of the com- monly cited definitions of high risk but does not comment as to which may be more or less suitable [2]. Various definitions will vary in terms of precision, discrimination, calibration, and ease of calculation. The venerable D’Amico classification and its variants are easy to determine with a glance at a medical record but yield highly heterogeneous groups [3]: By this definition, a man with a low-volume, Gleason 8, PSA 4 tumor may be placed in the same group as a man with a PSA 32, Gleason 9 tumor in multiple cores. A specific drawback of this definition is the inclusion of cT2c as a determinant of high risk. In one analysis of the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry, 24% of men in contemporary practice were classified as high risk, but >40% of these were in the high-risk group only because of stage cT2c; in fact, these patients had lower recurrence rates after surgery than those classified as intermediate risk [4]. As pointed out in the review [2], variations of the D’Amico classification are endorsed by guidelines on both sides of the Atlantic; however, definitions based on a multivariable analysis of pretreatment risk factors, such as the Cancer of the Prostate Risk Assessment (CAPRA) score or various published nomograms, are preferable for predicting tumors with uniformly aggressive biology. One drawback to nomograms in this setting is the lack of consistent score thresholds accepted to define high risk [5]. A stricter definition of high risk will naturally identify a smaller proportion of all diagnosed men, but given the relative numbers of men diagnosed with versus dying of prostate cancer in screened populations, it is appropriate to focus the most intense therapeutic efforts on a relatively small proportion of men. A point worth emphasizing is that in screened populations, men with high-risk disease tend to be older and frequently are not offered potentially curative local therapy (see [6]). However, older men with high-grade disease, even those diagnosed in their 80s, face a substantial risk of cancer-specific mortality in the absence of local therapy [7]. Treatment decisions should reflect tumor risk characteristics and patient comorbidity rather than age per se. DOI of original article: 10.1016/j.eururo.2012.02.031 * Tel. +1 415 885 3660; Fax: +1 415 885 7443. E-mail address: mcooperberg@urology.ucsf.edu. 0302-2838/$ – see back matter # 2012 Published by Elsevier B.V. on behalf of European Association of Urology. doi:10.1016/j.eururo.2012.03.037