Introduction: Update on the Treatment of Prostate Cancer

INTRODUCTION Update on the Treatment of Prostate Cancer: The Role of Adjuvant Hormonal Therapy Michael K. Brawer, MD Supplement Editor, Update on the Treatment of Prostate Cancer: The Role of Adjuvant Hormonal Therapy Northwest Prostate Institute at Northwest Hospital, Seattle, WA [Rev Urol. 2004;6(suppl 2):S1-S2] © 2004 MedReviews, LLC n the last two decades there have been numerous changes in the treatment of prostate cancer. With advances in early detection, primarily driven by prostate-specific antigen (PSA) measurement, improvements in therapeutic approaches for clinically localized disease and earlier utilization of androgen deprivation therapy have been widely adopted. Both the incidence of and, more recently, the rate of mortality from prostatic carcinoma in the United States have declined. Although it is too early to state definitively, the drop in mortality may be related to earlier diagnosis and aggressive, effective therapy. Despite these encouraging data, our most common approaches to clinically localized disease result too frequently in failure, which initially manifests as a biochemical recurrence. For example, the 10-year PSA recurrence rate following radical prostatectomy has been reported anywhere between 27% and 53%.1–5 Other therapeutic approaches, such as external beam radiation therapy and brachytherapy, also have unacceptably high failure rates. Stamey and associates6 eloquently demonstrated that the extent of Gleason grade 4 and 5 carcinoma was the best predictor of failure following radical prostatectomy. Indeed, these authors demonstrated that other predictors of failure include advanced clinical stage and PSA levels greater than 10.0 ng/mL. The role of adjuvant therapy is to increase the cure rate of traditional therapies, such as surgery or radiation. By definition, adjuvant therapy is utilized prior to the documentation of persistent disease. That is, it is administered either before (neoadjuvant), concomitant with, or soon after the primary therapeutic strategy, I ‘Casodex’ and ‘Nolvadex’ are trademarks of the AstraZeneca group of companies. VOL. 6 SUPPL. 2 2004 REVIEWS IN UROLOGY S1 Introduction continued without evidence (such as an elevated PSA level) of recurring disease. The argument for adjuvant therapy is that it extends the therapeutic margin of conventional therapy, which may be achieved by obliterating either microscopic deposits of cancer outside the surgical/radiation field or subclinical metastatic disease. Adjuvant or neoadjuvant therapy for prostate cancer primarily treated with surgery has not been shown to be effective, but efficacy has been demonstrated in men treated with radiation therapy. Bolla and colleagues7 and Pilepich and associates8 have demonstrated significant enhancement in disease-free survival, and in many cases, in overall survival in men treated with hormonal therapy as an adjunct to radiation therapy. Advantages of adjuvant therapy have been best demonstrated in carcinoma of the breast. Numerous studies and meta-analyses have demonstrated that adjuvant therapy, primarily with tamoxifen, results in significant reduction of tumor recurrence and mortality as compared to local therapy alone.9 For example, in a meta-analysis of 55 trials of women treated with tamoxifen (Nolvadex) S2 VOL. 6 SUPPL. 2 2004 for 5 years in an adjuvant setting, recurrence decreased 47% and mortality was 26% lower than with local therapy alone. These two fundamental observations, the impressive results from androgen deprivation as an adjuvant to radiation therapy and the established role of adjuvant hormonal therapy in breast cancer, provide the basis for widespread trials in prostate cancer. Bicalutamide (Casodex), an oral, nonsteroidal anti-androgen, represents an ideal candidate for such investigations. AstraZeneca has undertaken the largest prostate cancer trial in history, investigating the role of bicalutamide in an adjuvant setting. This international, prospective, randomized, placebo-controlled trial involves over 8,000 men undergoing radical prostatectomy, radiation therapy, and watchful waiting as primary therapies. This supplement to Reviews in Urology, made available by an educational grant from AstraZeneca, updates our readership with the rationale for, design of, and results from this major investigation. I am indebted to my colleagues, all leaders in their field, for providing REVIEWS IN UROLOGY an excellent summary of this important investigation. References 1. 2. 3. 4. 5. 6. 7. 8. 9. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591-1597. Zincke H, Oesterling JE, Blute ML. Long-term (15 years) results after radical prostatectomy for clinically localized (stage T2c or lower) prostate cancer. J Urol. 1994;152:1850-1857. Trapasso JG, deKernion JB, Smith RB, Dorey F. The incidence and significance of detectable levels of serum PSA after radical prostatectomy. J Urol. 1994; 152:1821-1825. Ohori M, Goad JR, Wheeler TM. Can radical prostatectomy alter the progression of poorly differentiated prostate cancer? J Urol. 1994; 152:1843-1849. Catalona WJ, Smith DS. Cancer recurrence and survival rates after anatomic radical retropubic prostatectomy for prostate cancer. J Urol. 1998; 160:2428-2434. Stamey TA, McNeal JE, Yemoto CM, et al. Biological determinants of cancer progression in men with prostate cancer. JAMA. 1999; 281:1395-1400. Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med. 1997;337:295-300. Pilepich MV, Caplan R, Byhardt RW, et al. Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol.1997;15:1013-1021. Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1992;339:1-14.