Introduction

INTRODUCTION LHRH Agonists: Contemporary Issues Michael K. Brawer, MD Northwest Prostate Institute, Northwest Hospital, Seattle, WA [Rev Urol. 2004;6(suppl 8):S1-S2] © 2004 MedReviews, LLC ith the exception of skin cancer, prostate cancer is the most common malignancy among men in the United States. It remains the second leading cause of cancer deaths, accounting for approximately 10% of all cancer-related mortality in US men.1 Since the early 1990s, the epidemiology and management of prostate cancer has profoundly changed, both in the United States and in other developed countries, due in part to the development and widespread use of the prostate-specific antigen (PSA) screening test.1,2 Each year increasing numbers of men are diagnosed with prostate cancer in general, and early-stage disease in particular, and the age at diagnosis continues to decrease.1-4 Currently, more than two-thirds of men are diagnosed with clinically localized disease, and the rate of men presenting with advanced disease continues to decrease.5-8 Between 1992 and 2001 the incidence rate of prostate cancer increased 3.2% (P < .05) among men under age 65 and decreased 4.4% (P < .05) among those over age 65.9,10 Thus the pool of younger men who have been treated for localized prostate cancer and who may develop disease recurrence is increasing.10 Surgery and radiation remain the primary treatment modalities for early stage prostate cancer. Radical prostatectomy rates have increased but the median age of patients treated with this surgery has decreased concomitant with the changing epidemiology of the disease.10 As more and more men are diagnosed earlier, their longevity is increasing, which allows for the possibility of disease recurrence and the need to determine the appropriate therapy for metastatic disease. Androgen W VOL. 6 SUPPL. 8ºº2004ººººREVIEWS IN UROLOGYººººS1 Introduction continued deprivation has been shown to be effective in a number of clinical settings. Luteinizing hormone-releasing hormone (LHRH) agonists alone or in combination with an antiandrogen have become the treatment of choice for androgen ablation in patients with advanced prostate cancer and have been associated with significant therapy improvements. Although some treatment options remain controversial, it is clear that much progress has been made in the successful identification of disease states amenable to various new and evolving treatment regimens. In September 2004, a roundtable was held in Chicago, Illinois, to discuss contemporary issues surrounding the use of LHRH agonists for patients with prostate cancer. Five leading experts in the field with knowledge of the clinical aspects of the disease and of the scientific literature met to share their expertise on prostate cancer, the current state of the art in hormone therapy for localized and advanced prostate cancer, and issues of reimbursement and managed care. The following supplement is based on the presentations from that meeting. I begin the supplement with an overview of the development and changing methods of androgen deprivation therapy (ADT) for patients with high-risk and advanced prostate cancer. The improvement in the management of such patients treated with ADT is discussed with the conclusion that both in the adjuvant and neoadjuvant setting, early ADT for patients with more aggressive prostate cancer may increase the cure rate of conventional therapy. Judd W. Moul, MD, follows with a discussion of the need for and ways in which to broaden the definition of “advanced” prostate cancer in view of the changing epidemiology of the disease. It is suggested that a more contemporary definition should include patients with stages C and D1 (T3, T4, and any T N1) in addition to those with widespread osteoblastic or softtissue metastases or stage D2 disease. Treatment alternatives are outlined and the importance of stratifying the risk of progression is stressed relative to treatment options. The developmental history and the efficacy of a new class of compounds called antiandrogens is then critically reviewed by Gerald W. Chodak, MD. The availability of these compounds presents a nonsurgical way to achieve maximal androgen blockade (MAB) by interfering with the production of androgen by the testes and the adrenal gland. Results of individual and meta-analyses of clinical trials of MAB are evaluated in terms of survival and time to progression. Dr. Chodak suggests that MAB should be included as a reasonable option for the treatment of patients with metastatic prostate cancer. Next, the biologic rationale for administering hormonal therapy and radiotherapy for men with localized prostate cancer is evaluated by Mack Roach, III, MD. Using data from 7 completed randomized clinical trials of neoadjuvant hormonal therapy (NHT) administered with external beam radiotherapy (EBRT), Dr. Roach concludes that the preponderance of data supports the use of NHT with EBRT for men with intermediate risk whereas high-risk patients require additional longer-term hormonal therapy. Yet to be determined, however, is the optimal time and duration of hormone therapy for these men. S2ººººVOL. 6 SUPPL. 8ºº2004ººººREVIEWS IN UROLOGY And finally, M. Ray Painter, MD, describes the changing face of urology from a business standpoint. What the practicing urologist can expect in 2005 and 2006 based on current and proposed legislation, and recommendations about how to ensure full payment for all services provided are presented. In addition, Dr. Painter provides a practical and detailed guide to implementing new electronic medical records for documentation, billing, and coding patient information. I thank all my colleagues for their excellent contributions to this supplement and for sharing their expertise in this challenging era of prostate cancer treatment. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8-29. Moul JW. Treatment options for prostate cancer: part I-stage, grade, PSA, and changes in the 1990’s. Am J Manag Care. 1998;4:1031-1036. D’Amico AV, Moul J, Carroll PR, et al. Cancerspecific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era. J Clin Oncol. 2003;21:2163-2172. Catalona WJ, Smith DC, Radiff TL, et al. Detection of organ-confined prostate cancer is increased through prostate-specific antigenbased screening. JAMA. 1993;270:948-954. Newcomer LM, Stanford JL, Blumenstein BA, Brawer MK. Temporal trends in rates of prostate cancer: declining incidence of advanced stage disease, 1974 to 1994. J Urol. 1997;158:1427-1430. Stephenson RA. Population-based prostate cancer trends in the PSA era: data from the Surveillance, Epidemiology, and Ed Results (SEER) Program. Monogr Urol. 1998;19:3-19. Farkas A, Schneider D, Perrotti M, et al. National trends in the epidemiology of prostate cancer, 1973 to 1994: evidence for the effectiveness of prostate-specific antigen screening. Urology. 1998;52:444-448. Moul JW. Treatment of metastatic prostate cancer. Braz J Urol. 2000;26:132-145. Ries LAG, Eisner MP, Kosary CL, et al. SEER Cancer Statistics Review 1975-2001. National Cancer Institute. Bethesda, MD, 2004. Moul JW, Wu H, Sun L, et al. Epidemiology of radical prostatectomy for localized prostate cancer in the era of prostate-specific antigen: an overview of the Department of Defense Center for Prostate Disease Research national database. Surgery. 2002;132:213-219.