Prostate Cancer Screening and Surgical Management of Localized Disease

Highlights From the 27th Annual Congress of the European Association of Urology

Meeting Review Prostate Cancer Screening and Surgical Management of Localized Disease Highlights From the 27th Annual Congress of the European Association of Urology, February 24-28, 2012, Paris, France [ Rev Urol. 2012;14(3/4):87-89 doi: 10.3909/riu0556] ® © 2013 MedReviews , LLC KEY WORDS Prostate-specific antigen • Prostate biopsy • Radical prostatectomy T he 27th Annual European Association of Urology (EAU) Congress was held in Paris, France, from February 24-28, 2012. There were many exciting presentations on prostate cancer screening and the surgical management of localized disease. Screening Prostate-specific antigen (PSA)-based screening continues to generate significant controversy, in light of the seemingly divergent data from randomized trials.1-3 However, these differences might be explained by differences in study design between the European Randomized Study of Screening for Prostate Cancer (ERSPC), Göteborg populationbased randomized screening trial, and Prostate, Lung, Colorectal and Ovarian cancer screening trials. Reviewed by Stacy Loeb, MD, Department of Urology, New York University, New York, NY. Zhu and colleagues highlighted this issue using data from 2 different centers participating in the ERSPC.4 In Göteborg, randomization to the screening and control arms occurred prior to informed consent (effectiveness trial), whereas in Rotterdam, informed consent preceded randomization (efficacy trial). Correspondingly, a “healthy participant” bias was seen in Rotterdam, wherein both the screening and control arms had lower overall and prostate cancer-specific mortality rates than expected based on life tables. By contrast, in Göteborg, the screening arm had a greater prostate cancer-specific mortality benefit, and observed disease-specific mortality in the Göteborg control group was similar to expected data. These results highlight the importance of control group characteristics in interpreting screening trial results. Beyond total PSA levels, numerous presentations looked at other screening tests. For example, Heijnsdijk and colleagues used modeling to examine the performance of the Beckman Coulter Vol. 14 No. 3/4 • 2012 • Reviews in Urology • 87 40041700002_RIU0556.indd 87 12/02/13 2:29 PM 27th Annual Congress of the EAU continued Prostate Health Index (PHI) in a European male population aged 50 to 75 years undergoing screening every 4 years.5 The model predicted that using PHI in addition to the total PSA level would reduce negative biopsies by 29%, along with a 6% increase in quality-adjusted life-years and 12% increase in cost effectiveness. Several other studies looked at prostate cancer antigen 3 (PCA3), a urinary-based molecular test that recently received approval from the US Food and Drug Administration to help determine the need for repeat prostate biopsy. Accordingly, there was substantial discussion whether PCA3 may also have a future role in helping to guide initial prostate biopsy decisions. A presentation by Auprich and associates demonstrated how PCA3 cutoffs have different performance characteristics in the initial and repeat biopsy settings.6 There was also discussion about a possible role for imaging to help assess the need for prostate biopsy in the future. Ahmed and colleagues described the upcoming Patient Reported Outcomes Measurement Information System (PROMIS) study, which plans to enroll at least 500 men from multiple centers to undergo multiparametric magnetic resonance imaging (MRI) prior to a recommended prostate biopsy.7 This study will help to determine whether MRI picks up clinically significant lesions, and will provide important data on the costeffectiveness of incorporating MRI into screening protocols. Additional studies evaluated whether imaging could be used in combination with other markers to help determine the need for repeat biopsy in men with a prior negative biopsy. For example, among men with a prior negative biopsy, Di Silverio and colleagues reported that the combination of magnetic resonance spectroscopic imaging and PCA3 had better discrimination of repeat biopsy results compared to either test alone.8 Radical Prostatectomy With regard to treatment, BillAxelson and associates previously reported that radical prostatectomy improved survival over watchful outcome.11 In a novel presentation, Trinh and colleagues used decisioncurve analysis to examine the impact of hospital volume and surgeon volume on postoperative outcomes after radical prostatectomy based on data from Surveillance Epidemiology and End Results Medicare.12 Both hospital volume and surgeon volume were At the EAU Congress, new data were presented from the ERSPC Rotterdam demonstrating significantly higher progression-free, metastasis-free, and prostate cancer-specific survival rates after radical prostatectomy in men from the screening arm versus the control arm. waiting in a randomized trial of men with clinically localized disease.9 Because the majority of patients in that trial were diagnosed clinically, less has been published regarding the long-term outcomes of radical prostatectomy in men diagnosed through screening. At the EAU Congress, new data were presented from the ERSPC Rotterdam demonstrating significantly higher progressionfree, metastasis-free, and prostate cancer-specific survival rates after radical prostatectomy in men from the screening arm versus the control arm.10 Interestingly, reduced tumor volume in the screening arm appeared to be an important determinant of improved radical prostatectomy outcomes. These results suggested that screening and treat- significantly associated with the likelihood of postoperative complications, blood transfusions, urinary incontinence, and erectile dysfunction. Interestingly, Trinh and associates showed that the impact of hospital volume on these outcomes was more informative for older patients with comorbidities who have a greater baseline risk of complications, whereas hospital volume was less critical for young healthy patients at lower risk for perioperative complications.12 The same authors also compared robotic and open approaches with radical prostatectomy using data from the Nationwide Inpatient Sample (October 2008-December 2009).13 Overall, 61% of prostatectomies during this period were performed robotically, providing In addition to the benefits of early detection through screening, prior studies have also demonstrated a strong association between surgical volume and prostatectomy outcome. ment are complementary, in that screening enables more effective treatment through a reduction in tumor volume at diagnosis. In addition to the benefits of early detection through screening, prior studies have also demonstrated a strong association between surgical volume and prostatectomy useful data on contemporary trends in utilization. They also showed that robotic procedures tended to be concentrated at high-volume centers. After matching with propensity scores, robotic prostatectomy was associated with fewer transfusions and inpatient perioperative complications compared 88 • Vol. 14 No. 3/4 • 2012 • Reviews in Urology 40041700002_RIU0556.indd 88 12/02/13 2:29 PM 27th Annual Congress of the EAU with open prostatectomy. However, important data, including tumor features and long-term functional outcomes, were not available. Also, due to the retrospective nature of the study, there may have been other important differences between the groups. Indeed, Briganti and associates showed the problems associated with nonrandomized comparisons of open and robotic prostatectomy.14 They found that patients undergoing open prostatectomy were significantly older with more preoperative erectile dysfunction and higher rates of nonorganconfined disease than in a robotic prostatectomy population. Additionally, the performance and extent of pelvic lymph node dissection were significantly greater in open cases, which could also have an impact on outcomes. Overall, it will be difficult to rigorously assess the long-term comparative effectiveness of these two approaches in the absence of prospective, randomized data. 7. 8. References 1. 2. 3. 4. 5. 6. 9. Andriole GL, Crawford ED, Grubb RL 3rd, et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst. 2012;104:125-132. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360: 1320-1328. Hugosson J, Carlsson S, Aus G, et al. Mortality results from the Göteborg randomised populationbased prostate-cancer screening trial. Lancet Oncol. 2010;11:725-732. Zhu X, Van Leeuwen P, Holmberg E, et al. Efficacy vs. effectiveness study design within the European Randomized study of Screening for Prostate Cancer: consequences for prostate cancer incidence, overall mortality and disease-specific mortality. Eur Urol Suppl. 2012;11:e269. Heijnsdijk E, Huang J, Denham D, De Koning H. The cost-effectiveness of prostate cancer detection using Beckman Coulter Prostate Health Index. Eur Urol Suppl. 2012;11:e260. Auprich M, Haese A, De La Taille A, et al. Development of novel PCA3 cut-offs for initial and repeat 10. 11. 12. 13. 14. biopsy using different statistical approaches within a US-European multi institutional cohort. Eur Urol Suppl. 2012;11:e263. Ahmed H, Gabe R, Kaplan R, et al. Multi-parametric magnetic resonance imaging in the diagnosis and characterization of prostate cancer prior to first biopsy in men at risk: the PROMIS study. Eur Urol Suppl. 2012;11:e824. Di Silverio F, Salciccia S, Busetto GM, et al. Is prostate biopsy still necessary? Eur Urol Suppl. 2012;11:e261. Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011;364:17081717. Loeb S, Zhu X, Schröder F, Roobol M. Long-term radical prostatectomy outcomes among participants from the ERSPC Rotterdam. Eur Urol Suppl. 2012;11:e682. Vesey SG, McCabe JE, Hounsome L, Fowler S. UK radical prostatectomy outcomes and surgeon case volume: based on an analysis of the British Association of Urological Surgeons Complex Operations Database. BJU Int. 2012;109:346-354. Trinh Q-D, Shariat S, Sammon J, et al. The effect of hospital vs. surgical volume on outcomes after radical prostatectomy: a head-to-head comparison using decision-curve analyses. Eur Urol Suppl. 2012;11:e677. Trinh Q-D, Sammon J, Ghani K, et al. Perioperative outcomes of robot-assisted radical prostatectomy vs. open radical prostatectomy. Eur Urol Suppl. 2012;11:e679. Briganti A, Gallina A, Suardi N, et al. Why the outcomes of initial cases of open and robotic surgeons cannot be compared? Importance of patients selection. Eur Urol Suppl. 2012;11:e784. Vol. 14 No. 3/4 • 2012 • Reviews in Urology • 89 40041700002_RIU0556.indd 89 12/02/13 2:29 PM