Prostate Cancer
Reviewing the Literature
RIU0288_11-20.qxd 11/20/06 2:50 PM Page 232 Pediatric Urology continued Retractile Testis—Is It Really a Normal Variant? 2. Agarwal PK, Diaz M, Elder JS. 3. Hack WW, Meijer RW, Van Der Voort-Doedens LM, et al. Previous testicular position in boys referred for an undescended testis: further explanation of the late orchidopexy enigma? BJU Int. 2003;92:293-296. Wyllie GG. The retractile testis. Med J Aust. 1984;140:403-405. J Urol. 2006;175:1496-1499. The investigators examined 204 retractile testes (40 unilateral, 82 bilateral) in 122 boys. A retractile testis was defined as a testis above the scrotum that could be manipulated easily into the scrotum and remain there without traction until the cremasteric reflex was induced. Most boys were followed annually, except in cases with an undescended testis and contralateral retractile testis. A scrotal orchiopexy was performed on the retractile testis to avoid the need for long-term follow-up and to prevent future ascending testes. All boys in this study had a minimum follow-up of 1 year. Of the 204 retractile testes, 61 (30%) descended (mean age, 6.6 years), 66 (32%) became undescended, and 77 (38%) remained retractile. Of the 62 retractile testes with an inelastic spermatic cord, 35 (56%) became undescended. A processus vaginalis was found in 8 of 61 orchiopexies (13%). A fibrous remnant of the processus vaginalis was found in the majority of the patients. Prostate Cancer Conflicting Insights Into the Role of Watchful Waiting in the Management of Adenocarcinoma of the Prostate Reviewed by Danil V. Makarov, MD, Alan W. Partin, MD, PhD The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins Medical Institutions and Hospital, Baltimore, MD [Rev Urol. 2006;8(4):232-234] © 2006 MedReviews, LLC In boys 7 years or older, the testis had a 19% chance of remaining retractile, compared with a 44% chance in boys younger than 7. Agarwal and colleagues found that a retractile testis would more likely descend in a boy older than 7 years than in a boy younger than 7. In boys 7 years or older, the testis had a 19% chance of remaining retractile, compared with a 44% chance in boys younger than 7. If a boy had 1 retractile testis and 1 descended testis at the start of the study, then 69% of the retractile testes descended, and only 32% required an orchiopexy. On the other hand, those with 1 retractile testis and 1 undescended testis at the start of the study had a greater likelihood of the retractile testis requiring an orchiopexy for the undescended testis. This study is important because it demonstrates that the retractile testis is not a normal variant; it has a significant risk of undergoing ascent and residing outside of the scrotum. These findings highlight the need for long-term follow-up in boys with retractile testes, given that 32% of these retractile testes become ascending testes. The risk is greater in boys younger than 7 years and in those with an inelastic spermatic cord. References 1. 232 Fenton EJM, Woodward AA, Hudson IL, Marschner I. The ascending testis. Pediatr Surg Int. 1990;5:6-9. VOL. 8 NO. 4 2006 REVIEWS IN UROLOGY pproximately 20% to 30% of men undergoing prostate-specific antigen (PSA) testing in referral and screened populations will have well- to moderately differentiated (Gleason score 6) and small volume ( 0.5 cm3) tumors. These tumors are thought to be less significant than larger, higher-grade tumors and demonstrate a long natural history.1-3 Expectant management of prostate cancer is based on the assumption that therapy (as well as potential complications) in these A The results of two important studies with differing conclusions regarding the expectant management of localized prostate cancer have recently been released. patients can be deferred without adverse consequence until it is no longer necessary (patient becomes old enough that prostate cancer is unlikely to be the cause of mortality) or until changes in the characteristics of the tumor warrant immediate treatment. Expectant management can be an active curative treatment approach if patients are treated aggressively upon follow-up determination of pathological progression.2,4 The results of two important studies with differing conclusions regarding the expectant management of localized prostate cancer have recently been released. RIU0288_11-20.qxd 11/20/06 2:50 PM Page 233 Prostate Cancer Treatment of Localized Prostate Cancer: A Survival Analysis of SEER-Medicare Data Wong Y, Wan F, Montagnet C, et al. Abstract (#271) presented at the 2006 American Society of Clinical Oncology (ASCO) Prostate Cancer Symposium, February 24–26, 2006. Wong and colleagues from the Fox Chase Cancer Center (Philadelphia, PA) presented some very provocative data at the 2006 ASCO Prostate Cancer Symposium. Because of increasing interest in expectant management and the dearth of randomized data comparing immediate treatment with deferred treatment, they examined patients with clinically localized prostate cancer from the Surveillance, Epidemiology, and End Results (SEER) Medicare database. They wanted to determine whether there was a demonstrable difference between the outcomes of men undergoing immediate treatment for clinically localized prostate cancer and those managed with observation. The researchers examined a cohort of 49,375 men between the ages of 65 and 80 years who had been diagnosed with clinically localized prostate cancer in the period from April 1991 to September 1999. The men had to have survived for at least 1 year after diagnosis. The primary endpoint examined was overall survival, defined as the time from diagnosis to Medicare date of death. Data were available on clinical stage (which they called “tumor size”), dichotomized into T1 to T2a versus T2b to T2c, and on tumor grade, dichotomized into well differentiated (Gleason score 2-4) versus moderately differentiated (Gleason 5-7). Poorly differentiated tumors were excluded. Treatment was defined as having a claim for either radical prostatectomy or radiation therapy (with or without androgen deprivation therapy) within 6 months of diagnosis. Men without Medicare claims for either of these procedures were considered to be undergoing observation. Men treated with androgen deprivation alone were excluded from analysis. Median age at diagnosis was 72 years. Median survival for the observation group was 133 months, whereas median survival was not reached for the treatment group. Controlling for known predictors of treatment using propensity scores, the hazard ratio for the risk of death for the overall observation group (n 12,468) compared with the treatment group (n 36,907) was 1.24 (95% confidence interval [CI], 1.18-1.30). Several interesting subgroups also demonstrated statistically significantly improved Cox proportional hazard ratios in the treatment versus observation groups: African Americans 1.37 (95% CI, 1.20-1.25), those with clinical stage T1 to T2a and welldifferentiated pathology 1.13 (95% CI, 1.02-1.25), and the elderly (diagnosed at 75-80 years of age) 1.41 (95% CI, 1.31-1.51). Also fascinating was that the hazard ratio for surgery versus observation was 2.33 (95% CI, 2.13-2.55) and for radiation versus observation was 1.09 (95% CI, 1.051.55). A comparison between surgery and radiation was not reported, though such numbers might imply an advantage to surgery over radiation. As might be expected, an interaction was observed in the full cohort between the clinical stage (“size”) of a tumor and its likelihood of treatment, as well as between biopsy grade and treatment (P .0005). A sensitivity analysis of the full cohort demonstrated that, to eliminate the advantage of treatment versus observation, an unknown confounder would need to be unequally distributed between the groups or increase the hazard ratio for death by at least 50% in both, implying that within this data set the described relationships are robust. The researchers concluded that their study supports the immediate treatment of men diagnosed with prostate cancer. These results are indeed very surprising and generated a great deal of media coverage upon release. Surprising was that such a study—in an older group of men with a short follow-up, examining overall survival (not prostate cancer–specific survival), and having a very inclusive definition of “observation” (men in this group could still have received treatment as it occurred 6 or more months after diagnosis)—would come out so strongly in favor of treatment. Although those factors work against the demonstration of treatment benefit, several ambiguities in the definition of the observation group could conspire to make the benefit in treatment seem greater than it actually is. The first is pathology; the well differentiated group with Gleason grade 2 to 4 would no longer exist today, as many pathologists no longer diagnose Gleason 2 to 4 on needle biopsy.5 In addition, the second group contains a wide variety of varying Gleason grades. Does this imply that some men with Gleason 7 tumors are not receiving treatment for their prostate cancer? Is the observation group enriched for Gleason 7 tumors? Lacking also are data on pretreatment PSA level in these patients. A significant difference in PSA levels between the groups (higher in the observation group) could be driving some of the benefit. Most importantly, the data do not describe the follow-up routine for the observation group, and, therefore, cannot exclude patients who were simply lost to follow-up. These results, although provocative and most certainly true in many populations, contain ambiguities that make them difficult to generalize to all men with prostate cancer. Delayed Versus Immediate Surgical Intervention and Prostate Cancer Outcome Warlick C, Trock BJ, Landis P, et al. J Natl Cancer Inst. 2006;98:355-357. VOL. 8 NO. 4 2006 REVIEWS IN UROLOGY 233 RIU0288_11-20.qxd 11/20/06 2:50 PM Page 234 Prostate Cancer continued Warlick and colleagues from Johns Hopkins wanted to answer a slightly different question than the previous group. An active expectant management approach is rarely used in men diagnosed with prostate cancer, so as not to lose the window of opportunity for early cure. Rather than compare survival among patients who had been treated versus those who had been observed, they wished to determine whether there was a difference in pathologic outcomes among men undergoing radical prostatectomy in an expectant management protocol as compared with those undergoing immediate surgery. Between January 1, 1995 and February 1, 2005, 320 men had been enrolled in the expectant management program at Johns Hopkins. This program is offered to any man who has had a new diagnosis of prostate cancer made by a 12 core needle biopsy that demonstrates cancer with Gleason score 6 or less involving fewer than 3 cores and less than 50% of any individual core. At entry these men must have had PSA density (PSAD) less than 0.15 ng/mL/g. Thirtyeight patients from the expectant management program (median age, 61 years) who had ultimately undergone radical prostatectomy were compared with 150 men (median age, 61 years) matched for age and PSA level who had undergone immediate surgery. Delayed surgical intervention took place at a median of 26.5 months (95% CI, 17-32 months; range, 12-73 months) after diagnosis, whereas the immediate surgery group underwent surgical intervention at a median of 3 months (95% CI, 2-4 months; range, 1-9 months) after diagnosis. “Noncurable cancer” was defined as pathology associated with a less than 75% chance of remaining free of prostate cancer at 10 years after surgery. Noncurable cancer was diagnosed in 9 (23%) of the 38 patients from the expectant management group and in 24 (16%) of the 150 men in the immediate intervention group. After adjustment for age and PSAD in a Mantel-Haenszel analysis, the risks of noncurable cancer associated with delayed and immediate intervention were not statistically significantly different (relative risk 1.08; 95% CI, 0.55-2.12; P .819, twosided Cochran-Mantel-Haenszel statistic). Age, PSA level, and PSA density were all statistically significantly associated with the risk of noncurable cancer (P .030, .013, and .008, respectively). The researchers concluded that delayed prostate cancer surgery for patients with small, lower-grade prostate cancers followed expectantly does not seem to compromise the surgical curability of these cancers. Wong and colleagues come out for the immediate treatment of low-grade, clinically localized prostate cancer, whereas Warlick and colleagues advocate watchful waiting as a potential option for the same disease. One might justifiably wonder how these two groups could arrive at such 234 VOL. 8 NO. 4 2006 REVIEWS IN UROLOGY different conclusions. One could argue that the Johns Hopkins group does not assess the survival outcomes of these patients, and thus presents immature data that might in time demonstrate a survival advantage to immediate intervention. However, what is more likely is that the Johns Hopkins group presents the results of a study in which patients were carefully selected and followed according to a defined algorithm. Although expectant management is not a good management strategy for all prostate cancer, it clearly can be applied in the setting of low-grade and low-stage disease in patients who will be carefully followed. References 1. 2. 3. 4. 5. Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA. 1994;271:368-374. Bastian PJ, Mangold LA, Epstein JI, Partin AW. Characteristics of insignificant clinical T1c prostate tumors. A contemporary analysis. Cancer. 2004;101: 2001-2005. Humphrey PA, Keetch DW, Smith DS, et al. Prospective characterization of pathological features of prostatic carcinomas detected via serum prostate specific antigen based screening. J Urol. 1996;155:816-820. Allaf ME, Carter HB. Update on watchful waiting for prostate cancer. Curr Opin Urol. 2004;14:171-175. Epstein JI. Gleason score 2-4 adenocarcinoma of the prostate on needle biopsy: a diagnosis that should not be made. Am J Surg Pathol. 2000;24:477-478. Overactive Bladder Health Care Usage, Botulinum Toxin for Overactive Bladder Reviewed by Akira Furuta, MD, PhD, Michael B. Chancellor, MD Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA [Rev Urol. 2006;8(4):234-235] © 2006 MedReviews, LLC lthough overactive bladder (OAB) is ranked among the 10 most common chronic medical conditions in the United States, the level of OAB-associated medical treatment remains largely unknown. Investigators at the Florida International University School of Public Health asked a simple but relevant question: How many patients with OAB actually seek medical help? A