Surgery Provides Better Oncologic Outcomes than Radiation for the Treatment of Prostate Cancer.

Opposing Views Surgery Provides Better Oncologic Outcomes than Radiation for the Treatment of Prostate Cancer CON “It is not what you don’t know that gets you into trouble, It’s what you know for sure, that just ain’t so.” dMark Twain M ANY urologists seem to “know” that radical pros- tatectomy (RP) provides greater survival than radiotherapy (RT), and as a result there has been an increase in the performance of surgery for high risk prostate cancer in the last 5 years. 1 This hypothesis is supported by literature consisting of (flawed) retrospective studies. 2 Space does not allow me to address these studies in detail but virtually all of them would be characterized as providing a “low level of confidence” using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) Cochrane type approach. 3 Many of these studies are prone to a huge risk of attribu- tion bias because a death was classified “due to prostate cancer” if this diagnosis was listed on any of the top 3 lines of the death certificate. 4 Since patients treated with RT are more likely to die of other causes, they are at greater risk for death to be attributed to prostate cancer even if they did not die of this disease. This risk is magnified by the large size of these population based studies (eg 20,000) such that an attribution bias error of 2% could translate into increased hazard ratios that would result in statistically significant dif- ferences. Also, many studies used SEER (Sur- veillance, Epidemiology and End Results) data that are unreliable for such comparative studies because before 2010 biopsy Gleason score was used for RT cases but pathological Gleason score was used for RP cases. Furthermore, accurate prostate specific antigen data were not available. 5 Other reasons for doubting the usefulness of these studies are discussed in our recent critical anal- ysis of this topic. 3 Despite the many shortcomings of these popula- tion based studies, in a recent meta-analysis Wallis et al asserted that approximately 90% had a low risk of bias. 2 A careful review of these studies THE JOURNAL OF UROLOGY ® O 2016 by A MERICAN U ROLOGICAL A SSOCIATION E DUCATION j www.jurology.com AND R ESEARCH , I NC . reveals major differences between the patients treated with RP and those treated with RT (bias), thus completely discrediting their assertion and the conclusions of their study. Using a novel approach based on a respect for treatment with RT combined with androgen deprivation therapy (ADT), sup- ported by level I evidence and accounting for various types of bias, we reached different conclu- sions than Wallis et al. Based on the most reliable studies comparing RP to RT with or without ADT, when men were treated in accordance with the current standard of care, the median difference in 10-year cause specific survival (CSS) was 1% (95% CI 2% to 7%, p¼0.24). 3 We concluded that this residual 1% CSS difference favoring RP over RT could easily be explained by failure to adjust for several factors associated with a worse outcome. 3 We further concluded that the results with dose escalated image guided RT might be superior to those expected with RP for men with high risk prostate cancer, if long-term ADT was used in accordance to NCCNO guidelines. 3 The only major trial establishing the efficacy of RP compared to “watchful waiting” showed that the benefits appeared to be limited to men younger than 65 years. In contrast, multiple phase III trials have shown that for men who need treatment the most, RT is highly beneficial, even for those with T3 dis- ease and those older than 70 years. The fact that several studies have shown that older men would be expected to have more advanced disease than younger men supports the hypothesis that there may be unique biological interactions between ADT and RT in older men. 3 In conclusion, although limited data from a single phase III trial suggest the benefits of RP exist only for men younger than 65 years, there is a robust body of phase III trials, dating back 30þ years, mostly populated by men older than 65 years, providing level I evidence of the benefit of RT. 3 The best data, based on current standards of care, suggest that the 10-year CSS rates from prostate cancer are essentially identical following http://dx.doi.org/10.1016/j.juro.2016.05.007 Vol. 196, 308-311, August 2016 Printed in U.S.A.