Innovative Strategies Proposed at the Western AUA Meeting

75th Annual Meeting, Western Section, American Urological Association

MEETING REVIEW Innovative Strategies Proposed at the Western AUA Meeting Highlights From the Annual Meeting of the Western Section of the American Urological Association September 26-30, 1999, Monterey, California [Rev Urol. 2000;2(1):4-10] Key words: Androgens • Cancer, prostate • Benign prostatic hyperplasia (BPH) • Carcinoma, renal cell • Carcinoma, transitional cell • Transplantation • Imaging techniques • Erectile dysfunction M ore than 500 physicians attended the 75th Annual Meeting of the Western Section, American Urological Association, a meeting that has grown substantially since 1925, when only three papers were presented. Abstracts were submitted under several categories, including adrenal gland, bladder, calculi, infections, neurourology, kidney, urethra, pediatrics, penis, incontinence, prostate, testis, and ureter. This meeting review will focus on the important contributions made on these major topics. Faculty are listed on page 10. Prostate Cancer Androgens. The winner of the coveted Joseph F. McCarthy/Circon ACMI Essay Contest this year was entitled “Antisense TRPM-2 oligodeoxynucleotides delay progression to androgen-independence after castration and enhance chemosensitivity in the androgen-dependent Shionogi tumor model.” TRPM-2 was initially reported as an androgen-repressed gene upregulated in prostate cells after castration; however, its functional role in apoptosis has been poorly defined. The Reviewed by Allan J. Pantuck, MD, and Arie S. Belldegrun, MD, FACS, University of California, Los Angeles, School of Medicine. investigators sought to characterize changes in TRPM-2 gene expression following androgen ablation and during progression to androgen independence, to define its functional role in apoptosis, and to investigate the effects of antisense TRPM-2 oligodeoxynucleotide therapy and its ability to delay time to androgen-independent recurrence using the androgendependent Shionogi tumor model. The provocative data presented suggest that TRPM-2 is an apoptosis-associated cell survival gene up-regulated by androgen ablation that confers resistance to both hormone therapy and chemotherapy and is not an androgen-repressed gene. The expression of TRPM-2 was found to accelerate lymph node prostate cancer tumor progression to an androgen and chemoresistant phenotype following castration. Furthermore, using antisense therapy to block TRPM-2 mRNA expression, the authors were able to enhance castration- and paclitaxel-induced cell death and to delay time to androgen independence. Moreover, the combination of antisense TRPM-2 therapy with antisense Bcl-2 oligodeoxynucleotides synergistically enhanced these cytotoxic effects. These findings provide a strong rationale for clinical trials using antisense/gene therapy combi- nation targeting of these and other antiapoptotic genes for patients with advanced and recurrent prostate cancer. [Dr Gleave] Using a strategy of intermittent androgen suppression for patients with prostate cancer, a total of 87 patients requiring long-term androgen withdrawal therapy were treated since February 1987 with combined androgen blockade. Treatment was continued for a minimum of 6 months until a serum prostate-specific antigen (PSA) nadir was observed. Treatment was then stopped until a serum PSA of 10 to 20 ng/mL was reached. Treatment cycles were then repeated until androgen independence was noted. The authors found only a 26% rate of androgen independence at 48 months, and they conclude that intermittent ablation is an acceptable approach for controlling prostate cancer for this cohort of patients while offering improved quality of life during the “off-therapy” phase and reducing treatment toxicity and cost. Interestingly, the authors found that with each advancing cycle, the average time to nadir increased while the length of cycle and percent of time off treatment decreased, suggesting a declining response to treatment over time. The optimal time to continued on page 7 4 REVIEWS IN UROLOGY WINTER 2000 AUA Meeting continued from page 4 start therapy and duration of treatment are key elements of intermittent therapy, but they remain poorly defined. In vitro and in vivo data from UCLA suggest that longer treatment cycles that continue until a PSA nadir has been reached may, in fact, hasten progression to androgen independence. We eagerly await the results of randomized, prospective trials that are currently under way in Vancouver and elsewhere to determine whether intermittent androgen deprivation affects survival in an adverse or beneficial way. [Dr Goldenberg] Further evidence to support the idea that shorter cycles may be beneficial was presented. The results of hip and spine bone mineral density studies suggest a trend toward diminished bone density in prostate cancer patients as duration of androgen deprivation therapy increases, placing them at increased risk for fracture. The author recommends bisphosphonate supplementation for patients on prolonged androgen deprivation. [Dr Terris] Screening. Although the PSA level remains one of the best screening modalities for malignancy, problems still remain with its lack of sensitivity and specificity. Measurement of complexed PSA (cPSA) and percent free PSA (%fPSA) may be used for men with a total PSA (tPSA) of less than 4.0 ng/mL to determine which men below the standard cutoff for PSA level are at risk for carcinoma. [Dr Brawer] Some investigators found that PSA transition zone density was the best of the PSA modifications for predicting cancer in the PSA gray zone of 4 to 10 ng/mL. Although transition zone density performed better than PSA density, the increased sensitivity was small and of questionable clinical significance. [Dr McRae] Prostate volume criteria to determine the optimal strategy for each patient were suggested. For men with small prostates (less than 30 g), the authors found that PSA performed as well as other derivatives. For men with midsize prostates (30 to 60 g), PSA density performed better than PSA alone, and for men with large prostates (larger than 60 g), %fPSA outperformed both PSA and PSA density. They found no added value in determining transition zone PSA density. [Dr Fagelson] Biopsy. While there were many abstracts presented that proposed new strategies for performing prostate biopsy (such as including extreme lateral and transition zone biopsies), there was only one that proposed a new way of interpreting prostate biopsies. The role of detecting telomerase activity in prostate biopsy specimens in the diagnosis of prostate cancer was examined. In this small series, a higher number of biopsy cores taken from radical prostatectomy specimens were positive for cancer based on telomerase activity than when based on histology. [Dr Ramin] Benign Prostatic Hyperplasia Several papers reviewed new and developing technologies using minimally invasive surgery for benign prostatic hyperplasia (BPH). One investigator presented data on his experience using interstitial laser coagulation with the Indigo diode laser as well as with transurethral needle ablation (TUNA), which uses radiofrequency energy to deliver thermal energy to the prostate. Early 6-month data suggest that both technologies are clinically effective in the treatment of patients with symptomatic BPH and can be performed in an ambulatory setting using local prostate block and monitored intravenous sedation. [Dr Yew] An animal study using a thermal prostatic stent showed that this temporary, nitinol-based endoluminal stent is capable of delivering thermal energy to the prostate while maintaining patency of the urethral lumen postoperatively. [Dr Gill] Much-needed, updated outcomes data for the gold-standard transurethral radical prostatectomy (TURP) in the 1990s were shared. This contemporary series showed decreases in transfusion requirements, hospital stay, catheter time, and both early and late complications when compared with historical series, making TURP more competitive with some of the newer, less invasive surgical technologies. [Dr Borboroglu] Renal Cell Carcinoma Information from two excellent posters may impact how we manage renal cell carcinoma (RCC) surgically. Electrocautery in conjunction with intraoperative ultrasonography was used to define the borders of small, intraparenchymal lesions during partial nephrectomy. Surface eschar marks using electrocautery could delineate intraparenchymal tumor boundaries because of the posterior shadowing the eschar produces on ultrasonography. This technique will be helpful for locating and excising small, centrally located lesions, making them amenable to nephron sparing. [Dr M. Feng] Attendees heard an argument against the routine performance of adrenalectomy during radical nephrectomy. He presented data on 511 patients undergoing radical nephrectomy for renal cell carcinoma at UCLA. Although the majority of these patients had advanced-stage RCC, only 29 patients had ipsilateral adrenal metastasis. Review of preoperative CT scans demonstrated a specificity of 99.6% and a negative predictive value of 99.4%, suggesting that if the CT scan is negative, adrenalectomy should not be performed routinely. [Dr Tsui] continued on next page WINTER 2000 REVIEWS IN UROLOGY 7 AUA Meeting continued Imaging The impact of technologic advances in imaging was evident in areas as diverse as female urology and pediatrics. The use of dynamic MRI for the evaluation and grading of pelvic prolapse and pelvic floor relaxation was discussed. In this series of 164 consecutive female patients presenting with pelvic or urethral pain, dynamic MRI was found to provide a comprehensive visualization of the female pelvis and to be more accurate than physical examination alone in the diagnosis of pelvic prolapse. In addition to being less invasive, dynamic MRI was touted as being cost-effective, since it obviates the need to perform cystourethrography, pelvic ultrasonography, and intravenous urography in the evaluation of the female pelvis. [Dr Comiter] Spiral CT imaging can provide renal parenchymal volume measurements. Calculated volumes were compared with true swine kidney volumes determined by water displacement. This technique may form the basis for providing an objective means to assess and clinically manage pediatric hydronephrosis. [Dr W. Feng] These papers by Dr Comiter and Dr Feng won 3rd place in the Joseph McCarthy and 2nd place in the Miley B. Wesson essay contests, respectively. Transplantation Is there a difference in renal allograft function if live donor nephrectomy is performed laparoscopically or with an open surgical procedure? In the realm of transplant, much interest was evident concerning the use of laparoscopic versus open live donor nephrectomy. By all parameters monitored, including serum creatinine, postoperative acute tubular necrosis, need for hemodialysis, and allograft rejection, laparoscopy performed as well as open surgery. However, the laparoscopic approach did result in Main Points • Combined antisense/gene therapy targeting antiapoptotic genes may be useful for patients with advanced and recurrent prostate cancer. • To determine whether men whose prostate-specific antigen (PSA) level is below the standard cutoff are at risk for prostate cancer, measuring complexed and percent free PSA may be helpful. • Both interstitial laser coagulation and transurethral needle ablation are effective in the management of symptomatic BPH. • Telomerase activity in prostate biopsy specimens can aid in the diagnosis of prostate cancer. • Dynamic MRI is more accurate than physical examination alone in the diagnosis of pelvic prolapse. increased warm ischemia time, which remains a concern. [Dr Novotny] Antegrade balloon endopyelotomy in eight renal transplant patients who developed persistent ureteral stenosis was examined. This approach was successful in 75% of patients, which is better than that obtained by balloon dilation and less morbid than open surgical revision. Mean followup, however, was only 10 months. Clearly, long-term patency needs to be evaluated. [Dr Bretan] needed that better control important variables such as etiology of erectile dysfunction and age. [Dr Ito] Two presentations provided data on the efficacy of sildenafil (Viagra) following radical prostatectomy. Presenters agreed that sildenafil appears to benefit patients after either unilateral or bilateral nerve-sparing prostatectomy but not following non– nerve-sparing procedures. [Dr M. Feng, Dr Dalkin] Transitional Cell Carcinoma Erectile Dysfunction A placebo-controlled study looked at the effects of Arginmax in 41 patients with mild to moderate erectile dysfunction. Arginmax is a natural dietary supplement whose proposed biochemical actions include up-regulation of the nitric oxide pathway. The supplement is a combination of ginkgo biloba, American and Korean ginseng, L-arginine, multivitamins, zinc, and selenium. Of the treatment participants, 89% reported improvement in the ability to maintain an erection during intercourse, and 75% reported improved satisfaction in their sex life, as measured by the International Index of Erectile Function (compared with only 18% in the placebo group for improvement in both function and satisfaction). The two groups, however, were not well described, and larger studies are Investigators at the University of Southern California looked at urethral tumor recurrence following cystectomy for transitional cell carcinoma with different types of urinary diversion. The results of 694 male patients were evaluated. Urethral recurrence developed in 7% of patients, with prostatic urethral and stromal involvement presenting the greatest risk of recurrence. However, urethral recurrence developed in only 2% of patients undergoing orthotopic diversion. This was statistically significant and was particularly evident in the high-risk patients (those who had prostatic stromal tumor involvement). Although patients in the orthotopic group had less median follow-up than those with cutaneous diversions, all patients with fewer than 2 years’ follow-up were excluded from evaluation. It is unclear why the orthotopic continued on page 10 8 REVIEWS IN UROLOGY WINTER 2000 AUA Meeting continued Other Contributors group should do better, although it may be that maintaining the urethra’s function as a urinary conduit or that a substance secreted by the ileum is somehow protective. [Dr Stein] Bladder Trauma Criteria for CT cystography in evaluating patients for bladder injury were proposed. For patients with blunt trauma, CT cystography should be performed on all patients with either gross hematuria or a combination of microscopic hematuria and pelvic fracture. No injuries have been missed using this approach. [Dr. Ullrich] From the audience, Dr McAninch suggested that in order to diagnose bladder injuries accurately, retrograde filling of the bladder with contrast is necessary. One cannot rely on antegrade filling from intravenous contrast. ■ In addition to the Medical and Contributing Editors, the following authors contributed to this issue: Anurag K. Das, MD, FACS Associate Professor of Surgery/Urology Albany Medical College Albany, NY Jonathan L. Giddens, MD Fellow, Endourology New York University School of Medicine New York Alan J. Pantuck, MD Fellow, Urological Oncology University of California, Los Angeles, School of Medicine Penelope A. Longhurst, PhD Faculty for the 75th Annual Meeting of the Western Section of the American Urological Association Prodromos Borboroglu, MD, Naval Medical Center, San Diego Michael Brawer, MD, Northwest Prostate Institute, Seattle Peter Bretan, MD, University of California, San Francisco Craig Comiter, MD, University of California, Los Angeles Bruce Dalkin, MD, University of Arizona Health Sciences Center, Tucson James Fagelson, MD, University of Texas Southwest Medical Center, Dallas Mark Feng, MD, Kaiser Permanente, Los Angeles Waldo Feng, MD, University of California, Los Angeles Harcharan Gill, MD, Stanford University, Stanford, Calif Martin Gleave, MD, University of British Columbia, Vancouver S. Larry Goldenberg, MD, University of British Columbia, Vancouver Thomas Ito, MD, Honolulu Jack W. McAninch, MD, University of California, San Francisco Simon McRae, MD, Stanford University, Stanford, Calif Michael Novotny, MD, University of California at Davis, Sacramento S. Ramin, MD, Loma Linda Medical Center, Loma Linda, Calif John Stein, MD, University of Southern California, Los Angeles Martha Terris, MD, Stanford University, Stanford, Calif Ke-Hung Tsui, MD, University of California, Los Angeles Nathan Ullrich, MD, Harborview Medical Center, Seattle Jay Yew, MD, Kaiser Permanente, Los Angeles Associate Professor of Surgery/Urology Albany Medical College Research Associate Professor of Pharmacology Albany College of Pharmacy Albany, NY Kiarash Michel, MD Chief Resident, Department of Urology University of California, Los Angeles, School of Medicine Belur Patel, MD Postdoctoral Fellow/Clinical Instructor Department of Urology University of California, Los Angeles, School of Medicine Steven R. Potter, MD Resident The Brady Urological Institute The Johns Hopkins Hospital Baltimore Farhang Rabbani, MD, FRCSC Department of Urology Memorial Sloan-Kettering Cancer Center New York Mark D. White, MD Assistant Professor of Surgery/Urology Albany Medical College Albany, NY Scott I. Zeitlin, MD Assistant Clinical Professor of Urology University of California, Los Angeles, School of Medicine Amnon Zisman, MD Fellow in Urological Oncology University of California, Los Angeles, School of Medicine 10 REVIEWS IN UROLOGY WINTER 2000