New Findings in Prostate Cancer

8. RIU0455_10-22.qxd 10/22/09 4:29 PM Page 169 MEETING REVIEW New Findings in Prostate Cancer Highlights From the 24th Annual Congress of the European Association of Urology, March 17–21, 2009, Stockholm, Sweden [Rev Urol. 2009;11(3):169-172 doi:10.3909/riu0455] © 2009 MedReviews®, LLC Key words: Prostate cancer • Staging • Urinary incontinence • Erectile dysfunction • Pelvic lymph node dissection • European Randomized Study of Screening for Prostate Cancer (ERSPC) he 24th Annual Congress of the European Association of Urology (EAU) took place in Stockholm from March 17 to 21, 2009. Almost 11,000 participants were offered over 1000 abstracts, over 40 video sessions, and over 40 courses on contemporary issues. Major topics concerning prostate cancer included basic research, prognostic factors, surgical and functional outcome, and management of postoperative urinary leakage and erectile dysfunction. Important new research was presented on diagnosis, prognostic factors, therapy modalities, and surgical approaches. T Reviewed by Franklin E. Kuehhas, MD, Department of Urology, Medical University of Vienna, Vienna, Austria; Bob Djavan, MD, PhD, Department of Urology, New York University School of Medicine, New York, NY. Diagnosis Interesting data regarding the importance of the ratio of free to total prostate-specific antigen (f/t PSA) for prostate cancer detection were presented by the Swedish branch of European Randomized Study of Screening for Prostate Cancer (ERSPC). The f/t PSA ratio has been claimed useful in selecting men at a higher risk for prostate cancer. A low ratio has been advocated as a diagnostic tool to select men for biopsy, especially men with slightly elevated (3-10 ng/mL) or normal (1-3 ng/mL) serum PSA levels. The study evaluated the risk of later developing prostate cancer in men with a serum PSA level between 1 and 2.99 ng/mL related to the f/t ratio. A total of 2239 men were included in the analysis. The authors concluded that even if men with a low f/t PSA ratio have a higher risk for being diagnosed with prostate cancer, the results from this study do not support selective screening of men with serum PSA levels of 1 to 3 ng/mL.1 In ERSPC, men with an initial PSA value lower than 3.0 ng/mL were not biopsied (with very few exceptions). Considering the prostate cancer detection rate reported by the Prostate Cancer Prevention Trial for men with these low serum PSA values, the main question is whether applying a threshold leads to delaying or missing diagnosis that subsequently could lead to more potentially incurable prostate cancer cases or prostate cancer deaths. Roobol and colleagues presented data from the ERSPC trial that showed that in the cohort of men with a serum PSA level lower than 3.0 ng/mL, 5% of all men have prostate cancer after a mean follow-up of 9 years, and 0.07% died of their disease. The lowest rate of prostate cancer deaths was observed in men with a VOL. 11 NO. 3 2009 REVIEWS IN UROLOGY 169 8. RIU0455_10-22.qxd 10/22/09 4:29 PM Page 170 24th Annual Congress of the EAU continued serum PSA level of 2.0 to 2.9 ng/mL; the most likely explanation for this is the more rapid progression to a biopsy indication. The highest rate of death is observed in the group of patients with the lowest PSA values. The present data suggest that a very unfavorable number of men need to be biopsied to find 1 missed prostate cancer or to detect 1 deadly prostate cancer. Although we lack more specific tests to detect these rare cases in a curable phase, a PSA cutoff for prostate biopsy seems justified.2 Suspicious serum PSA levels after an initial negative biopsy result in a permanent burden for patients and urologists. The decreasing probability of positive results in re-biopsies involves 10% to 30% of tests. Therefore, Lunacek and colleagues3 combined magnetic resonance tomography (MRT) and magnetic resonance spectroscopy (MRS) prior to contrast-enhanced ultrasound-targeted and systemic grayscale biopsies to increase rates of positive re-biopsies. The conclusion of this analysis was that a combination of these imaging modalities may increase cancer detection rates in patients undergoing subsequent rebiopsy. Additionally, it was shown that this algorithm should be used in patients with suspicious serum PSA values and positive family history. Furthermore MRT and MRS can serve as an additional tool in following patients with watchful waiting. Staging Bökeler and coworkers4 presented data on a new method of lymph node dissection. Radioisotope-guided lymph node dissection has been shown to provide a better sensitivity in detecting lymph node metastases compared with the standard lymphadenectomy of the obturatory region. The presented data demonstrated the efficacy of intraoperative sentinel lymph node (SLN) mapping 170 VOL. 11 NO. 3 2009 with a  probe for detecting lymph node metastases. Four hundred one patients with prostate cancer underwent SLN dissection using either an isolated laparoscopic staging procedure or during open retropubic prostatectomy. A transrectal ultrasound-guided injection of 99mTc nanocolloid was performed 16 to 24 hours prior to surgery. During surgery, the lymph nodes in the obturator fossa were routinely dissected, and, in addition, remaining SLNs were identified with the help of intraoperative  probing and subsequently removed. Of 401 patients, 9 patients that would not have been detected by standard lymphadenectomy had lymph node metastases. SLN resection can be seen as a valid tool for an exact prostate cancer staging and might help reduce morbidity compared with extended field lymph node resection without reducing sensitivity. An interesting contribution by Walz and colleagues5 was the headto-head comparison of nomograms predicting the probability of lymph node invasion in patients undergoing extended pelvic lymph node dissection. The Briganti nomogram was compared with the updated Partin tables and Cagiannos nomogram. Of the 173 patients who underwent radical prostatectomy combined with extended pelvic lymph node dissection, 12 had lymph node invasion (6.9%). The Briganti nomogram achieved a receiver operating characteristic (ROC) curve of 0.88 versus the Partin tables (0.85) and the Cagiannos nomogram (0.83). The Briganti nomogram and the Partin tables provide highly accurate predictions of probability of lymph node invasion during radical prostatectomy. Therefore, these 2 tools should be used to identify those patients in whom pelvic lymph node dissection can be safely spared. REVIEWS IN UROLOGY Therapy Modalities Robot-assisted prostatectomy (RAP) has been gaining widespread acceptance worldwide and is now the most common treatment modality for localized prostate cancer in the United States. Studies have shown that experienced surgeons have a learning curve of around 50 RAP procedures before obtaining proficiency. However, the learning curve of a minimally invasive fellowship–trained surgeon has not been assessed. Cheetham and colleagues6 showed that there is no learning curve after comprehensive fellowship training in robotic surgery. Urologic surgeons who receive fellowship training in robotic surgery can perform RAP and other robotic procedures as safely and efficiently as experienced surgeons. A group from the Karolinska University Hospital (Stockholm, Sweden) presented its data on the development of inguinal hernia after RAP compared with open radical retropubic prostatectomy.7 The literature shows that 15% to 20% of patients who undergo radical prostatectomy with open technique through a lower midline incision develop postoperative inguinal hernia. This study, however, showed that the cumulative incidence of postoperative inguinal hernia in the RAP group was 5.5% at 48 months compared with 16.7% in the group of patients who underwent open surgery. The incidence of postoperative inguinal hernia formation can be significantly reduced by using robot-assisted surgery. The use of high intensity focused ultrasound (HIFU) as a primary therapy for localized prostate cancer is gaining acceptance. New data on the postintervention outcome after HIFU were presented at this year’s EAU congress. In a multi-institutional study, 763 patients with localized prostate cancer (T1-2) treated with curative intent and who underwent 8. RIU0455_10-22.qxd 10/22/09 4:29 PM Page 171 24th Annual Congress of the EAU no intervention prior to HIFU were included in the analysis. KaplanMeier analysis was performed to determine biochemical survival with failure defined according to both the 2006 Phoenix definition (nadir 2) and the Stuttgart definition (nadir 1.2), which is a new definition with good sensitivity (78%) and specificity (79%) in predicting clinical failure following HIFU. The authors concluded that HIFU provides encouraging biochemical control in patients not treated with hormone therapy. Five-year biochemical survival predicted by the Phoenix definition was 85%; the Stuttgart definition predicted an average of 70% of patients free of clinical failure after HIFU.8 Postoperative Urinary Incontinence and Erectile Dysfunction Along with erectile dysfunction, urinary incontinence is one of the major drawbacks of radical prostatectomy due to temporary or prolonged deficiency of the rhabdomyosphincter (RS). The current literature shows that anatomic reconstruction of the posterior aspects of RS goes along with a faster recovery of urinary continence following radical prostatectomy. New data demonstrated clearly that early continence was significantly improved in the group of patients who underwent the anatomic reconstruction of the posterior RS.9 The physiologic explanation of this result could be fixation of the urethra in the pelvis, tension-free anastomosis due to a posterior support, and reconstruction of a musculofascial plate, including Denonvilliers fascia, the posterior median raphe, and the dorsal wall of the RS. The musculofascial plate is a dynamic suspensory system for the postmembranous urethra. Following radical prostatectomy, a remarkable number of patients suffer from stress urinary incontinence (SUI). Different therapy modalities have been described to help patients deal with this problem. Seibold and colleagues10 presented their data on the injection of bulking agents as a minimally invasive treatment option for SUI. The injected agent was dextranomer/hyaluronic acid copolymer (DEFLUX®; Oceana Therapeutics, Inc., Edison, NJ), which has good biocompatibility and no tendency to migrate. After a mean follow-up of 30.7 months, all 21 patients were interviewed. Before DEFLUX injection, all patients had a mean of 3.3 pads/day. In the long-term follow-up, 2 patients (9.5%) reached the goal of no pads/day and were defined continent. However, 19 patients (90.5%) showed no improvement postinjection. The authors concluded that the injection of bulking agents is a minimal treatment option for SUI with a low complication rate; however, the costs for the amount of used substance and the very low success rate make this treatment modality advisable only in selected cases. Surgical treatment modalities for post–radical prostatectomy urinary incontinence should start after 24 months. Studies have shown that continence rates increase within this period and that no significant improvement should be expected after 24 months. The AdVance™ Male Sling System (retrourethral sling; American Medical Systems, Minnetonka, MN) offers for the first time a nonobstructive functional therapeutic approach for the major drawback of urinary incontinence. The 12-month results showed that the retrourethral sling is a safe and noninvasive treatment option for male incontinence. The results are better in patients with only mild to medium stress incontinence than for patients with severe incontinence. Even after radiotherapy, the functional retrourethral sling is a safe and minimally invasive treatment option. For good postoperative outcome, a good preoperative evaluation of the patient’s incontinence with an extensive assessment of the sphincter region is required.11 Prognostic Factors Controversy remains about the relationship between obesity and prostate cancer. The current literature, predominantly from the United States, suggests that an increased body mass index (BMI) is a significant predictor of adverse pathologic findings in patients treated with open radical prostatectomy. An analysis to determine whether an increased BMI is a predictor of advanced pathology in European men included 1538 patients who underwent open radical prostatectomy.12 The results of the study clearly show that BMI was not related to extracapsular extension, seminal vesical invasion, lymph node invasion, and positive surgical margin. The authors concluded that obese patients who are candidates for open radical prostatectomy should not expect worse pathologic findings after surgery than nonobese men. Differences in patient weight and height between North America and Europe may explain the lack of adverse effect of elevated BMI in this cohort of European men. Phosphodiesterase type 5 inhibitors (PDE5i) are an established treatment option for erectile dysfunction (ED) following radical prostatectomy. Several studies in men with ED and lower urinary tract symptoms (LUTS) with benign prostatic hyperplasia (BPH) suggest that PDE5i could improve both erectile function and urinary bother symptoms. Gacci and coworkers13 presented data on the role of vardenafil in continence recovery after bilateral nerve-sparing radical prostatectomy. In this placebocontrolled study, it was demonstrated VOL. 11 NO. 3 2009 REVIEWS IN UROLOGY 171 8. RIU0455_10-22.qxd 10/22/09 4:29 PM Page 172 24th Annual Congress of the EAU continued that vardenafil can improve continence recovery after nerve-sparing surgery. The daily use of vardenafil seems to provide better continence rates, although it does not seem to influence the time needed to achieve full continence. This year’s 24th annual EAU Congress in Stockholm presented a great opportunity for urologists to present their newest data on contemporary issues. The information and the results presented were very promising. Barcelona is host to the 25th annual EAU Congress from April 16 to 20, 2010. 2. 3. 4. 5. 6. References 1. 172 Carlsson S, Aus G, Hugosson J, et al. The risk of being diagnosed with potentially incurable prostate cancer in men with PSA 1-3 ng/mL is not related to the ratio of free PSA. Eur Urol Suppl. 2009;8:163. Abstract 171. VOL. 11 NO. 3 2009 7. REVIEWS IN UROLOGY Roobol MJ, Aus G, Auvinen A, et al. How to screen for prostate cancer after 2008? PSA as a biopsy indicator, part II. Eur Urol Suppl. 2009;8:191. Abstract 284. Lunacek A, Simon J, Bernt R, et al. Increased rates of positive re-biopsies using a combination of MR-tomography and spectroscopy prior to contrast enhanced ultrasound targeted and systematic grey-scale biopsies—a retrospective analysis. Eur Urol Suppl. 2009;8:354. Abstract 935. Bökeler UW, Hennenlotter J, Kruck S, et al. Critical re-evaluation of a modified sentinel guided pelvic lymph node resection in prostate carcinoma: review of 401 consecutive cases. Eur Urol Suppl. 2009;8:125. Abstract 17. Walz J, Bladou F, Rousseau B, et al. A head to head comparison of nomograms predicting the probability of lymph node invasion in patients undergoing extended pelvic lymph node dissection. Eur Urol Suppl. 2009;8:125. Abstract 20. Cheetham PJ, Lee DJ, Natalin R, Badani KK. Does robotic surgery fellowship training eradicate the learning curve for robotic prostatectomy? Eur Urol Suppl. 2009;8:350. Abstract 919. Stranne CJ, Carlsson S, Johansson EM, et al. Inguinal hernia after robot assisted radical prostatectomy as compared to open radical retropubic prostatectomy for prostate cancer. Eur Urol Suppl. 2009;8:352. Abstract 925. 8. 9. 10. 11. 12. 13. Blana A, Brown SCW, Chaussy C, et al. Primary prostate HIFU without pretreatment hormone therapy: biochemical survival of 763 patients tracked with the @-registry. Eur Urol Suppl. 2009;8:333. Abstract 850. Salvaggio A, Granata AM, Gregori A, et al. Early continence recovery after laparoscopic radical prostatectomy with or without restoration of posterior rhabdosphincter: results of a randomized trial. Eur Urol Suppl. 2009;8:221. Abstract 403. Seibold J, Werther M, Amend B, et al. Stress urinary incontinence after radical prostatectomy: long term effects of endoscopic injection with dextranomer/hyaluronic acid copolymer. Eur Urol Suppl. 2009;8:338. Abstract 870. Bauer RM, Mayer ME, Soljanik I, et al. AdVance sling: results after 12 months. Eur Urol Suppl. 2009;8:336. Abstract 863. Isbarn H, Jeldres C, Budäus L, et al. The effect of body mass index on histopathological parameters; results of a large European contemporary consecutive open radical prostatectomy series. Eur Urol Suppl. 2009;8:363. Abstract 971. Gacci M, Ierardi A, Delle Rose A, et al. Vardenafil can improve continence recovery after bilateral nerve sparing prostatectomy: a double blind placebo-controlled trial. Eur Urol Suppl. 2009;8:363. Abstract 972.