Should Treatment with Radiation and Androgen Deprivation Therapy be Considered the 'Gold Standard' for Men with Unfavourable Intermediate- to High-risk and Locally Advanced Prostate Cancer?

Clinical Oncology 28 (2016) 475e478 Contents lists available at ScienceDirect Clinical Oncology journal homepage: www.clinicaloncologyonline.net Editorial Should Treatment with Radiation and Androgen Deprivation Therapy be Considered the ‘Gold Standard’ for Men with Unfavourable Intermediate- to High-risk and Locally Advanced Prostate Cancer? M. Roach, III Department of Radiation Oncology, University of California San Francisco (UCSF), Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA Received 7 March 2016; accepted 29 March 2016 The ‘gold standard’ for treating prostate cancer should be based on: (i) the degree to which there is level I evidence (from prospective phase III randomised trials) supporting its efﬁcacy; (ii) sound biological physical principles under- lying the treatment; (iii) generalisability, reproducibility and applicability to most of the patients diagnosed with localised prostate cancer and (iv) there are no competing therapeutic options that are proven to be more effective. Based on the ﬁrst three criteria, a very strong argument can be easily made that deﬁnitive radiotherapy [combined with androgen deprivation therapy (ADT) when appropriate] should be considered the ‘gold standard’ for managing clinically localised unfavourable intermediate- to high-risk prostate cancer [1]. For the fourth criteria there is contro- versy and that is the focus of this editorial. Although some studies focusing on biochemical [prostate-speciﬁc antigen (PSA)] control suggest that radiation-based treatments are as good or better than radical prostatectomy, different PSA failure deﬁnitions are used after these treatments so this area remains controversial [2e4]. Thus, I will focus my attention on overall survival and cause-speciﬁc survival (CSS) and use data from prospective phase III trials to justify appropriate care [1]. In the last 5 years there has been a substantial increase in the use of radical prostatectomy compared with radio- therapy for men with locally advanced disease, probably due to the belief by many urologists that ‘there is good evidence’ from population-based studies that radical pros- tatectomy offers a better survival rate than radiotherapy Author for correspondence: M. Roach III, Department of Radiation Oncology, University of California San Francisco (UCSF), Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, Suite H 1031, San Francisco, CA 94143-1708, USA. Tel: þ1-415-353-7181; Fax: þ1-415-353- E-mail address: mroach@radonc.ucsf.edu [5,6]. Space does not allow me to address these studies in detail, so I encourage readers to see our critical review of this topic [7]. An example of substantial bias found in these population-based studies is readily made obvious by a recent meta-analyses conducted by Wallis and colleagues [6,8]. In their ﬁrst ‘meta-analysis’, they assessed survival end points and asserted that 90% of the studies included in their meta-analysis had a ‘low risk of bias’ [6]. There seems to be a lack of relevance to what they meant by a ‘low risk of bias’ and what I mean by ‘bias’. Table 1 highlights a few examples of the shortcomings of their study, with addi- tional criticisms previously made [9]. Some of their biases included the fact that they systematically ignored the ﬂaws of poorly designed studies favouring radical prostatectomy while omitting higher quality studies that favoured radio- therapy. There are numerous other problems with many of these population-based studies comparing outcomes after radical prostatectomy and radiotherapy-based treatments. For example, the Surveillance Epidemiology and End Results (SEER) data used by many of these studies is unre- liable for comparing outcomes between radical prostatec- tomy and radiotherapy because before 2010 biopsy Gleason score was only available for radiotherapy patients, whereas pathological Gleason score was available for radical pros- tatectomy patients and accurate PSA data were not available [20]. In addition experts have reported that, using SEER data, major residual biases persisted, creating ‘improbable results’ and concluded ‘ . the results from observational studies of treatment outcomes should be viewed with caution’ [21]. Furthermore, adjustments based on Charlson co-morbidity index also seem to be inadequate, being best applied when populations are relatively homogeneous, such as those limited to a co-morbidity index score of 0 [22]. Also of great concern, in a number of studies a death was classiﬁed ‘due to prostate cancer’ if this diagnosis was listed http://dx.doi.org/10.1016/j.clon.2016.04.037 0936-6555/O 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.