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1131 EUROPEAN UROLOGY 63 (2013) 1128–1133 A total of 731 men agreed to participate in the trial; 364 were randomized to RP, and 367 were randomized to observation. At median follow-up of 10.0 yr, RP provided no benefit with respect to ACM (hazard ratio [HR]: 0.88; 95% confidence interval [CI], 0.71–1.08; p = 0.22; absolute risk reduction, 2.9 percentage points) or PCSM (HR: 0.63; 95% CI, 0.36–1.09; p = 0.09; absolute risk reduction, 2.6 percentage points). For men with PSA >10 ng/ml, subgroup analysis demonstrated that RP was associated with decreased ACM (HR: 0.67; 95% CI, 0.48–0.94) and PCSM (HR: 0.36; 95% CI, 0.15–0.89). overall and PCa-specific survival. The study also demonstrated higher rates of non-PCSM than had been previously suggested by other studies over similar time frames [2]. Such information is crucial when counseling men about the benefits of treatment. This study adds to mounting evidence that low-risk tumors may safely be observed and high-risk tumors should be treated. Conflicts of interest: The authors have nothing to disclose. References Experts’ comments: This study is truly pivotal because it is the first randomized trial to assess the impact of RP versus observation in the PSA era, an issue that remains important and unclear >17 yr after the study first opened. A prior Scandinavian trial largely performed in the pre-PSA era demonstrated improved PCa-specific survival [1] and, with longer follow-up, improved overall survival [2] in patients who received RP. However, the generalizability of this Scandinavian trial has been questioned because >80% of study participants were diagnosed by digital rectal examination. Although the PIVOT study is flawed (accrual goals were not met, and the investigators failed to account for differences in outcomes based on provider [3]), Wilt et al. report their results with 10 yr of median follow-up and demonstrate clearly that men with lower-risk cancers do not benefit from RP, a finding that is largely consistent with active surveillance trials [4]. Although this result is not surprising, several important findings are worth noting. Men with higher-risk PCa benefited from RP. Bone metastases were lower in the RP group than in the observation group, and patients with PSA >10ng/ml had improved Re: Postoperative Radiotherapy After Radical Prostatectomy for High-risk Prostate Cancer: Long-term Results of a Randomised Controlled Trial (EORTC Trial 22911) Bolla M, van Poppel H, Tombal B, et al. Lancet 2012;380:2018–27 Experts’ summary: This paper reports on the third large randomized trial exploring the value of adjuvant radiotherapy following radical prostatectomy for prostate cancer [1,2]. A total of 1005 patients from 37 European institutions were randomized. Eligible patients had pT2N0M0 or pT3N0M0 disease after surgery and at least one of the following additional risk factors: extracapsular extension, positive surgical margins, or seminal vesicle invasion. In total, 502 patients were assigned to immediate irradiation (60 Gy). For the 503 patients in the wait-andsee group, irradiation was deferred until biochemical progression had occurred. After 10 yr, 227 patients (45.1%) remained biochemically and clinically recurrence-free. Only [1] Holmberg L, Bill-Axelson A, Helgesen F, et al. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 2002;347:781–9. [2] Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011;364:1708–17. [3] Vickers AJ, Bianco FJ, Serio AM, et al. The surgical learning curve for prostate cancer control after radical prostatectomy. J Natl Cancer Inst 2007;99:1171–7. [4] Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010;28:126–31. Jonathan L. Silberstein*, James A. Eastham Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA *Corresponding author. Memorial Sloan-Kettering Cancer Center, Urology Service, Department of Surgery, 1275 York Ave., New York, NY 10021, USA. E-mail address: [email protected] (J.L. Silberstein). http://dx.doi.org/10.1016/j.eururo.2013.03.020 155 patients (30.8%) received salvage irradiation. Biochemical progression was more common in the wait-and-see group than the immediate irradiation group (61.8% compared with 39.4%), but this reduced risk did not translate into a survival benefit, as the two treatment groups did not differ with respect to progression-free survival (PFS), distant metastasis–free survival, or overall survival. Experts’ comments: It is already apparent that this important paper will be interpreted in two quite opposite ways. Radiation oncologists will highlight the improved biochemical-free survival in the immediate irradiation group and argue in favor of adjuvant therapy for patients with high-risk features after radical prostatectomy. Urologists will point to the lack of improvement in overall survival, clinical PFS, or distant metastasis, as well as the higher rate of late adverse effects in the patients randomized to immediate irradiation. What are we to conclude? Clearly, there is a population of patients who will benefit from early administration of radiotherapy after radical prostatectomy, that is, patients with extracapsular disease and positive margins. However, 1132 EUROPEAN UROLOGY 63 (2013) 1128–1133 if the prostate-specific antigen (PSA) remains undetectable, then a period of surveillance in this cohort may also be reasonable, especially as patients continue their functional recovery after surgery. In the era of ultrasensitive PSA testing, there may be a considerable period during which early salvage radiotherapy (eg, PSA 0.3 ng/ml) will provide the same survival outcome as adjuvant radiotherapy. Most important, Bolla et al. have shown us that many patients with these high-risk features do perfectly well with observation and do not require further intervention. At 10-yr follow-up, more than half of the patients (272 patients, 54% in the wait-and-see group) had no additional treatment. This is a population of patients who would have been overtreated had they undergone immediate irradiation, and therefore they avoided the inconvenience, expense, and morbidity of this intervention [3]. For now, many urologists (the gatekeepers for referral to radiation oncology) will interpret this study as showing no survival advantage for immediate irradiation and will observe high-risk patients after radical prostatectomy with a view to early salvage radiotherapy instead. That will certainly be our practice. References Conflicts of interest: The authors have nothing to disclose. http://dx.doi.org/10.1016/j.eururo.2013.03.021 Re: Effect of Abiraterone Acetate and Prednisone Compared with Placebo and Prednisone on Pain Control and Skeletal-related Events in Patients with Metastatic Castration-resistant Prostate Cancer: Exploratory Analysis of Data from the COU-AA-301 Randomised Trial Logothetis CJ, Basch E, Molina A, et al. events leading to discontinuation: 10% compared with 13%). The end points of the secondary analysis, on which the Lancet Oncology article is based, were occurrence of skeletal-related events and pain care. With a median follow-up of 20.2 mo, the combination of abiraterone acetate and prednisone favorably affected disease-related symptoms (ie, pain palliation, delay in pain progression, and delay to skeletal-related events) compared with placebo and prednisone. Abiraterone acetate and prednisone resulted in significantly more pain palliation (45% compared with 28.8%; p = 0.0005) and faster pain palliation (median time to palliation: 5.6 mo compared with 13.7 mo; p = 0.0018) than placebo and prednisone. Median time to occurrence of the first skeletal-related event was significantly longer with abiraterone acetate and prednisone compared with placebo and prednisone (25 mo compared with 20.3 mo; delay: 4.7 mo; p = 0.0001). Lancet Oncol 2012;13:1210–7 Experts’ summary: Logothetis et al. performed a secondary analysis of the landmark placebo-controlled phase 3 trial that led the US Food and Drug Administration to approve abiraterone acetate for use in the postchemotherapy setting (COU-AA-301). The study was designed as an international, multicenter, prospective, randomized trial comparing the survival effect of abiraterone acetate and prednisone with that of placebo and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one or two lines of chemotherapy (one of which was docetaxel-based) [1,2]. Eligible patients were randomly assigned (2:1) to receive either abiraterone acetate and prednisone (n = 797) or placebo and prednisone (n = 398) with an intention-to-treat purpose. Overall survival was the primary end point of this trial. Patients were encouraged to continue treatment until disease progression (on the basis of radiographic findings, clinical findings, or change in serum prostate-specific antigen [PSA] levels). Compared with placebo, abiraterone acetate significantly improved overall survival (14.8 mo compared with 10.9 mo; hazard ratio: 0.65), had a better PSA response (38% compared with 10%), and was better tolerated (grade 3–4 adverse [1] Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009;181:956–62. [2] Wiegel T, Bottke D, Steiner U, et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96–02/AUO AP 09/95. J Clin Oncol 2009;27:2924–30. [3] Abdollah F, Suardi N, Cozzarini C, et al. Selecting the optimal candidate for adjuvant radiotherapy after radical prostatectomy for prostate cancer: a long-term survival analysis. Eur Urol 2013; 63:998–1008. James B. Duthiea, Declan G. Murphya,b,* a Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia b Australian Prostate Cancer Research Centre, Epworth Healthcare, Richmond, Australia *Corresponding author. Division of Cancer Surgery, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia. E-mail address: [email protected] (D.G. Murphy). Experts’ comments: Prostate cancer (PCa) is the most commonly diagnosed cancer among men in the industrialized world. Metastatic bone disease is the most common cause of PCa pain and of serious skeletal-related events, defined as pathologic fractures, spinal cord compression, bone pain requiring palliative radiotherapy, and orthopedic surgery. Both bone metastases and skeletal-related events are associated with unfavorable prognosis and greatly affect quality of life. Numerous new drugs have been approved for patients with mCRPC, with variable efficacy on overall survival and secondary end points such as bone pain and skeletal-related events. This study provides convincing evidence that abiraterone acetate