The Journal of Urology
Volume 180, Issue 5 , Pages 1873-1875, November 2008

This Month in Adult Urology

published online 22 September 2008.

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Degarelix for the Treatment of Prostate Cancer 

Gonadotropin-releasing hormone (GnRH) agonists have been valuable in the treatment of prostate cancer for more than a decade but few data are available on the use of luteinizing hormone-releasing hormone (LHRH) antagonists. In this randomized, open-label, dose finding study by Gittelman et al (page 1986) 127 patients received 200 mg of the novel GnRH receptor blocker degarelix followed by 12 doses of maintenance therapy with either 60 or 80 mg. Advantages of LHRH antagonists such as degarelix are fast suppression of gonadotropin secretion and the absence of an androgen flare response. With the 200 mg dose more than 80% of the patients reached testosterone levels of 0.5 ng/ml or less after 1 month. Serum testosterone levels after 1 year were less than 0.1 ng/ml for those on the 60 and 80 mg maintenance dose. The authors conclude that although 200 mg degarelix resulted in fast suppression of testosterone levels and that 80 mg was a satisfactory maintenance dose, they recommend testing a higher starting dose previously shown to achieve better castrate levels of testosterone. Whether GnRH antagonists have other advantages compared to LHRH agonists remains to be seen.

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Radiation Therapy for Prostate Cancer Increases Subsequent Risk of Bladder and Rectal Cancer 

In a multi-institutional study Nieder et al (page 2005) analyzed the SEER (Surveillance, Epidemiology and End Results) database to identify 243,082 men who underwent either radical prostatectomy or radiotherapy for prostate cancer between 1988 and 2003. They calculated the incidence of bladder and rectal cancer in both groups and found that the relative risk of bladder cancer was 1.88 after external beam radiotherapy (EBRT), 1.52 after brachytherapy, and 1.85 after combination external beam and brachytherapy radiation versus radical prostatectomy. The relative risks of rectal cancer after these treatments were 1.26, 1.08 and 1.21, respectively. The authors conclude that EBRT does increase the relative risk of bladder and rectal cancer compared to radical prostatectomy and that patients should be counseled accordingly. A limitation of generalizing such data is the development of newer modalities to deliver EBRT.

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Immunotherapy for Biochemical Prostate Cancer Recurrence 

Recent studies have suggested that therapy based on recruitment of dendritic cells may be effective for the treatment of prostate cancer. An alternate strategy is to develop human prostate cancer cells modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) and then administer this cellular immunotherapy. In this phase I-II multi-institutional safety study by Urba et al (page 2011) immunotherapy was well tolerated by 19 patients with no serious adverse effects using cells derived from PC-3 and LNCaP cell lines modified to secrete GM-CSF. A negative deflection of the prostate specific antigen (PSA) slope was seen in 84% of patients and there was an increase in median PSA doubling time from 28.7 weeks before treatment to 57.1 weeks after treatment. These patients exhibited increased production of antibodies to PC-3 in general and PC-3 associated filamin-B protein in particular. The authors conclude that GM-CSF immunotherapy has a favorable toxicity profile and may be of benefit for hormone refractory cancer.

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Nephron Sparing Surgery is Feasible for T1a Renal Cell Carcinoma in Kidney Transplant Recipients 

Currently the incidence of renal cell carcinoma (RCC) is increasing in the general population, probably due to increased detection by common imaging modalities such as ultrasound and computerized tomography. However, the incidence of RCC in kidney transplant recipients is similar to that of patients 20 to 30 years older without a transplanted kidney. Due to an increase in the age of donors and renal graft survival, urologists will see an increase in RCC in renal grafts. Chambade et al (page 2106) from Paris, France analyzed data on the treatment of RCC in transplant recipients. Of 2,050 kidney recipients between 1984 and 2006, 7 were diagnosed with RCC in the allograft, and 5 with T1a tumors smaller than 60 mm were included in the study. No postoperative complications were observed. Immunosuppressive therapy was not modified after surgery. No deterioration in renal function was noted at a mean followup of 17.4 months. The authors conclude that open nephron sparing surgery can be safely performed in kidney allograft recipients. The increase in donor age and reorganization of the criteria for kidney donors will probably lead to an increase in such surgeries.

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Testicular Pain After Laparoscopic Renal Surgery 

Testicular pain is one of the potential adverse effects of laparoscopic surgery that is not well reported. Gjertson and Sundaram (page 2037) from Connecticut and Indiana performed a prospective study of 64 male patients scheduled for laparoscopic kidney and adrenal surgery (68 procedures) starting in January 2006 to determine the incidence of testicular pain. Interestingly, there was a 55% incidence of ipsilateral testicular pain after donor nephrectomy and a 20% incidence after laparoscopic radical nephrectomy. The gonadal vein was preserved in 29 cases, and testicular pain developed in only one of these cases. The authors postulate that obstruction of the gonadal vein might potentially be the etiology. On a pain scale of 1 to 10, median intensity was 4. Preservation of the gonadal vein may be protective. The incidence of testicular pain after donor nephrectomy can be as high as 50% and it can occur after radical nephrectomy. The authors suggest alerting patients undergoing donor or radical nephrectomy of this potential adverse effect.

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Microsurgical Varicocelectomy for Isolated Asthenospermia 

Varicocele is the most common cause of male factor infertility and reduced fertility. The degree to which varicocelectomy improves pregnancy rates is open to debate. Boman et al (page 2129) from Montreal, Quebec, Canada performed a retrospective review of the records of 118 consecutive infertile couples in which the man presented with varicocele and isolated asthenospermia (less than 50% motile sperm) and either chose or refused varicocelectomy. Total sperm counts were similar in both groups. Mean sperm motility and mean total motile sperm count were significantly higher after varicocelectomy. The spontaneous pregnancy rate was also significantly higher in the varicocelectomy group compared to the control group (65% versus 32%). This study supports the use of varicocelectomy to treat infertile men with varicocele and isolated asthenospermia.

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Interstitial Cystitis/Painful Bladder Syndrome and Sexual Abuse 

Epidemiological data continue to show that a substantial proportion of patients with overactive bladder as well as interstitial cystitis/painful bladder syndrome have a history of sexual abuse. In this study by Seth and Teichman (page 2029) from Vancouver, BC, Canada 119 subjects had a history of sexual abuse greater than that of the general prevalence in society. When compared to subjects without a history of abuse, mean daytime frequency and nocturia were less while voided volumes were greater in the group with prior abuse. Female sexual function index scores were worse for all domains for subjects with a history of abuse as well as reports of tenderness and pain. The authors conclude that abused patients as a group present with fewer voiding problems but more pain versus those who were not abused.

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Does Normal Preoperative Urodynamic Testing Predict Postoperative Voiding Dysfunction? 

In a multi-institutional secondary outcome study from a prospective randomized controlled trial, Lemack et al (page 2076) evaluated whether data from preoperative urodynamics were predictive of voiding dysfunction 6 weeks after surgery or reoperation for takedown of a Burch suspension or pubovaginal sling. Among the 655 study cases voiding dysfunction developed in 57, including 8 in the Burch colposuspension group and 49 in the pubovaginal sling group. All 19 women who underwent surgical takedown were in the pubovaginal sling group. Statistical analysis of urodynamic parameters showed that no findings were associated with increased risk of voiding dysfunction in either group, including voiding pressure and degree of abdominal straining. The authors warn that this was a carefully selected group of patients, and those with higher residual urine volumes were not included in the study. Nevertheless the results suggest that videourodynamics cannot be routinely and nonselectively used to predict postoperative voiding dysfunction after these 2 procedures. The authors indicate that their findings may not be generalizable to other anti-incontinence surgeries.

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Office Dilation of the Female Urethra 

Dilation of the female urethra was historically thought to be of value in the treatment of a wide range of urinary symptoms such as recurrent urinary tract infections, pain and incomplete bladder emptying. Use of urethral dilation to treat urinary symptoms in the absence of urethral stricture has lost any scientific backing, and contemporary reports state that there is no value to this procedure for treating urgency or frequency in the absence of stricture. Santucci et al (page 2068) from Michigan and California used the National Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey and Healthcare Cost and Utilization Project-Nationwide Inpatient Sample databases from 1992 to 2000 to assess the extent to which practitioners still perform this office procedure. Using specified diagnostic procedure codes, they found that female urethral dilation is still common (roughly 929/100,000 patients). The overall costs of treatment exceeded $61 million annually. The authors warn that this is a claims based analysis with specific limitations. Yet while the diagnosis of genuine female urethral stricture is rare, with no more than 40 reports in recent literature, the number of female urethral strictures reported in claims databases is astonishingly in the hundreds of thousands, suggesting that urethral dilation is still being performed by many urologists to treat lower urinary tract symptoms in the absence of evidence of efficacy.

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Deficits in Urological Knowledge 

Mishail et al (page 2140) administered a questionnaire to attendings, residents, fellows and medical students at Stony Brook Medical Center in New York to determine how they treat patients with common urological complaints. The response rate was 50% (150/300 surveys). The questionnaire examined the urological education of third and fourth year medical students. Knowledge with regard to common conditions including hematuria, age specific PSA abnormality and overactive bladder was low for all groups. Answers indicated poor medical knowledge and a low likelihood of requesting a urological evaluation for these conditions. The authors conclude that general urological knowledge in the primary care setting is inadequate, and lack of medical knowledge of urological disorders has considerable negative impact on patient care when medical students have not received urological education. Future studies such as this are needed to correct what may be an increasing lack of knowledge about urological disease and proper management as well as referral. The authors did note that 20% of United States medical schools require clinical rotations in urology. The implications of this lack of urological knowledge for the general public are unclear.

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Best Practice Statement on Cryosurgery for the Treatment of Localized Prostate Cancer 

When the AUA guideline on the Management of Clinically Localized Prostate Cancer: 2007 Update was published, insufficient information was available to include cryosurgery in the data analysis. Therefore, the AUA convened a panel to develop the next level of evidence, a best practice statement, regarding the treatment of localized prostate cancer using cryosurgery. A best practice statement includes published data and expert opinion but a formal meta-analysis of the literature is not performed. Babaian et al (page 1993) reached a consensus that primary cryosurgery is an option for men who have clinically organ confined prostate cancer of any grade with negative metastatic evaluation. However, they note that case selection is a primary factor. Larger prostates may make it more difficult to uniformly achieve cold enough temperatures and previous transurethral resection may be a contraindication. Cryosurgery is a minimally invasive option for men who either do not want to undergo or are not good candidates for radical prostatectomy because of comorbidities such as obesity or history of pelvic surgery. The authors also made recommendations for maximizing the results of cryosurgery, such as using rapid freezing thermocouples to monitor temperature and a double freeze cycle, and obtaining a nadir temperature of −40C. Complications are outlined based on the available literature. Clinicians using cryosurgery are advised to review this best practice statement.

PII: S0022-5347(08)02069-7

doi:10.1016/j.juro.2008.08.010

The Journal of Urology
Volume 180, Issue 5 , Pages 1873-1875, November 2008

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