Prostate Cancer

News and Views from the Literature

RIU0382_06-17.qxd 6/17/08 4:39 PM Page 171 Prostate Cancer 100 Percentage 80 60 40 Motility Viability 20 Membrane Integrity Morphology (Head) Morphology (Tail) 0 0 1 2 3 Days 4 5 6 7 Figure 1. Motility, viability, morphology, and membrane integrity patterns exhibited by spermatozoa in culture for 7 days. Values represent the mean  standard error of 11 samples for each parameter at each time point. Reproduced with permission from Hossain AM et al, Fertil Steril. 2008;89:237-238. partner. For urologists harvesting sperm in such a situation, this can play havoc with their daily routine and schedule. Extended Culture of Human Spermatozoa in the Laboratory May Have Practical Value in the Assisted Reproductive Procedures Hossain AM, Osuamkpe CO, Nagamani M. definitely make life easier for those of us who have to rearrange our schedules on an almost daily basis when an egg retrieval is imminent. Prostate Cancer Fertil Steril. 2008;89:237-238. In an attempt to determine whether sperm function is impacted by keeping them in culture for an extended period after retrieval, Hossain and colleagues took 11 semen samples from supposedly normal men and kept them in culture for 7 days. They observed that the only function that significantly decreased after 24 hours was sperm motility, but even this parameter only demonstrated a decrease of approximately 20% (Figure 1). Sperm viability did not significantly decrease, which suggests that the majority of sperm that eventually became nonmotile at 24 hours in culture were still viable. Therefore, this pilot study suggests that sperm harvested from normal patients can be successfully retrieved and stored in culture for at least 24 to 48 hours or possibly longer before egg retrieval without significantly compromising their viability. Although the overall motility of the sperm did decrease after 24 hours, this was by only 20%, with the majority of the sperm still motile by that time. What obviously needs to be confirmed now is whether sperm from oligospermic patients behave in a similar manner. Such an observation in oligospermic men would Weighing the Risks: Prostate Cancer Versus Cardiovascular Disease Reviewed by Danil V. Makarov, MD, and Alan W. Partin, MD, PhD The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD [Rev Urol. 2008;10(2):171-173] © 2008 MedReviews, LLC he treatment of prostate cancer can be a very casespecific decision. Although it is clear that surgery provides a cure for some patients, there can be negative side effects that would make it the wrong therapeutic option for others. Some patients who are older and have low-volume prostate cancer may be excellent candidates for the expectant management of prostate cancer, whereas this would certainly be the wrong choice for a T VOL. 10 NO. 2 2008 REVIEWS IN UROLOGY 171 RIU0382_06-17.qxd 6/17/08 4:39 PM Page 172 Prostate Cancer continued younger, healthier man who could tolerate the side effects of active treatment. Radiotherapy also has proven efficacy for the treatment of prostate cancer. Although the addition of androgen deprivation therapy (ADT) to surgery has not demonstrated any therapeutic benefit, there is a sizable literature describing the improved prostate cancer–specific survival enjoyed by patients treated with a combination of ADT and radiotherapy. Recently a group from Brigham and Women’s Hospital in Boston has published several very important articles that add a caveat to the widely accepted notion that the addition of ADT in the treatment of prostate cancer is beneficial and benign. The first of these studies examined whether men with localized prostate cancer treated with ADT had an increased risk of cardiovascular-related mortality. not associated with a statistically significantly increased risk of cardiovascular mortality, although an overall increase was observed. The investigators conclude that use of ADT in patients undergoing prostatectomy increases the risk of cardiovascular mortality, which seems to supersede any potential benefit this treatment may have with regard to the treatment or control of prostate cancer. Androgen Deprivation Therapy for Localized Prostate Cancer and the Risk of Cardiovascular Mortality This article further explored the previous hypothesis that treatment for prostate cancer, including ADT, may exacerbate comorbidities, which may impact on a patient’s longterm outcome. It is an examination of the long-term follow-up of a trial randomizing men receiving radiotherapy to either receive 6 months of adjuvant ADT or not. This trial enrolled 206 men between the years 1995 and 2001 who had localized but unfavorable-risk prostate cancer (prostate-specific antigen  10 ng/mL, biopsy Gleason score  6, or evidence of extraprostatic extension on magnetic resonance imaging). Since their previously published work on this cohort,1 the median follow-up has reached 7.6 years (range, 0.511.0 years), with 74 deaths having occurred. The investigators confirmed their previous findings and report a significant increase in the risk of all-cause mortality (44 vs 30 deaths; HR 1.8; 95% CI, 1.1-2.9; P  .01) in men randomized to radiotherapy compared with those receiving radiotherapy and ADT. An analysis was also performed to determine whether the benefits of ADT changed depending on a patient’s comorbidity. In men with low comorbidity, the investigators found an increased risk in all-cause mortality when radiotherapy was performed without ADT (31 vs 11 deaths; HR 4.2; 95% CI, 2.1-8.5; P  .001). However, when men with moderate or severe comorbidity were examined, there was no significant difference in the risk of all-cause mortality (13 vs 19 deaths; HR 0.54; 95% CI, 0.27-1.10; P  .08). The investigators conclude that the addition of 6 months of ADT to radiotherapy results in an overall survival benefit but that this benefit seems to be limited to a subset of men who have low comorbidity. The implication of this finding is that the benefits of ADT in men with significant comorbidity are outweighed by the known dangers of this therapy. In healthy men without risk factors for cardiovascular disease the addition of ADT Tsai HK, D’Amico AV, Sadetsky N, et al. J Natl Cancer Inst. 2007;99:1516-1524. A group of 4892 patients were identified from the Cancer of the Prostate Strategic Urologic Research Endeavor database, a collection of patient outcomes from physicians in the community. Patients were not randomized to any treatment, but the data are thought to be reflective of actual community practice patterns. Of these 4892 patients, 3262 had been treated with radical prostatectomy, and 1630 had been treated with either radiotherapy (including external beam and brachytherapy) or cryotherapy for localized prostate cancer. ADT was defined as treatment with either a gonadotropin-releasing hormone agonist and/or an antiandrogen immediately before or within 6 months of the initiation of primary therapy. Among the men who received ADT, the median length of treatment was 4.1 months. The median follow-up for the entire group was 3.8 years. The investigators used competing risk analyses to assess simultaneously patients’ risk of mortality from prostate cancer, cardiovascular disease, or all-cause mortality. Use of ADT (adjusted hazard ratio [HR] 2.6; 95% confidence interval [CI], 1.4-4.7; P  .002) and age (adjusted HR 1.07; 95% CI, 1.02-1.1; P  .003) were associated with increased risk of mortality from cardiovascular causes in patients undergoing radical prostatectomy. In this same cohort of postprostatectomy patients, use of ADT was also associated with increased risk of all-cause mortality (adjusted HR 2.2; 95% CI, 1.4-3.5; P  .001), as were older age, diabetes, and Gleason score 8 or higher. In patients treated with radiation, brachytherapy, or cryotherapy the use of ADT was 172 VOL. 10 NO. 2 2008 REVIEWS IN UROLOGY Androgen Suppression and Radiation vs Radiation Alone for Prostate Cancer: A Randomized Trial D’Amico AV, Chen MH, Renshaw AA, et al. JAMA. 2008;299:289-295. RIU0382_06-17.qxd 6/17/08 4:39 PM Page 173 Prostate Cancer is so unlikely to cause added morbidity that the ADT shows a benefit because of the cancer control it provides. Although in the past a significant number of men with prostate cancer have been treated with ADT because this was thought to be noninvasive (and therefore safe) therapy,2 the scientific community has increasingly become aware of the deleterious effects of long-term ADT.3 The 2 studies discussed here further inform this discussion; clearly, ADT may not be beneficial for every patient. Therefore, although there maybe older, less healthy men in whom ADT would be appropriate, we must be careful to exercise great discretion and consider the potential harm we may do with this therapy. References 1. 2. 3. D’Amico AV, Manola J, Loffredo M, et al. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA. 2004;292:821-827. Cooperberg MR, Broering JM, Litwin MS, et al. The contemporary management of prostate cancer in the United States: lessons from the cancer of the prostate strategic urologic research endeavor (CapSURE), a national disease registry. J Urol. 2004;171:1393-1401. Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA. 2005;294:238-244. VOL. 10 NO. 2 2008 REVIEWS IN UROLOGY 173