This Month in Adult Urology

Article Outline

• Long Acting Testosterone Undecanoate Therapy for Hypogonadism
• Impact of Seminal Vesicle Invasion at Prostatectomy
• Surveillance and Deferred Treatment for Localized Prostate Cancer
• Drug Related Genetic Polymorphisms Affecting Adverse Treatment Reactions in Patients with Urothelial Cancer
• Robotic Partial Nephrectomy for Renal Hilar Tumors
• Sclerotherapy for Simple Renal Cysts
• Clinical and Consumer Trial Performance of SpermCheck Vasectomy
• How to Avoid Clean Intermittent Catheterization in Men With Ileal Bladder Substitution
• Somatostatin Analogue to Decrease Mucus Production After Enterocystoplasty
• Prognostic Factors of Percutaneous Nephrolithotomy Morbidity
• Copyright

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Long Acting Testosterone Undecanoate Therapy for Hypogonadism 

Androgen replacement therapy for hypogonadism can be administered through a variety of routes. Although there has been a recent shift toward topical preparations, there may be a need for a longer acting depot preparation that is well tolerated, effective and safe. Morgentaler et al (page 2307) report on a 6-month single arm, open label multi-institutional study of 130 men who received a novel preparation of testosterone that allows extended dosing. A dose of 750 mg testosterone undecanoate was administered intramuscularly at 0, 4 and 14 weeks. Of the subjects 94% achieved serum concentrations within the healthy young adult male range of 300 to 1,000 ng/dl. Predictably serum hemoglobin, hematocrit and prostate specific antigen (PSA) levels increased slightly. Maximum concentrations decreased within the supraphysiological range deemed safe by the Food and Drug Administration. Thus, using a lower dose compared to that approved in Europe, the authors conclude that this long acting preparation appears to be safe and well tolerated. The advantage of testosterone undecanoate over topical preparations is that it only needs to be given 5 times a year, perhaps leading to better compliance. It will be of interest to proceed with comparator trials with existing formulations to ascertain patient preference, efficacy and tolerability in addition to long-term safety.

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Impact of Seminal Vesicle Invasion at Prostatectomy 

SWOG (Southwest Oncology Group) 8794 is a randomized, prospective trial examining adjuvant radiation therapy versus post-prostatectomy observation. It is the largest series to date to examine the influence of negative prognostic factors such as seminal vesicle invasion. While the study was not powered specifically for seminal vesicle positive disease, intriguing data could be extracted from the study. Swanson et al (page 2453) reviewed the records of patients with a mean followup of 12.2 years, and found 139 with seminal vesicle involvement with or without capsular penetration and/or positive margins. These patients had poorer 10-year biochemical failure rate (33% vs 22%, p = 0.04), metastasis-free survival (70% vs 56%, p = 0.005) and 10-year overall survival (74% vs 61%, p = 0.02) compared to 286 without seminal vesicle invasion. Patients with seminal vesicle involvement who received adjuvant radiation therapy had an improvement in 10-year biochemical failure-free survival from 12% to 36%, overall survival from 51% to 71% and metastasis-free survival rate from 47% to 66%. This study strongly suggests that patients with positive seminal vesicle involvement after prostatectomy may benefit from early radiation therapy even without waiting for biochemical failure.

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Surveillance and Deferred Treatment for Localized Prostate Cancer 

Many countries are grappling with the use of active surveillance for prostate cancer and examining outcomes. In Sweden, a country noted for more conservative management of prostate cancer, surveillance was the primary treatment for 26% of men younger than 70 years in the National Prostate Cancer Registry from 1997 to 2002 with clinical stage T1 or T2 and PSA less than 20 (page 2423). The remaining patients were treated with radical prostatectomy (48%), radiotherapy (21%) and hormonal treatment (5%). In general patients on surveillance had local disease stage, grade and PSA values, and were older. After a median surveillance time of 4 years, 34% of the men received deferred treatment, which was most often radical prostatectomy (39%). Surveillance is common in Sweden but not nearly as prevalent as might have been expected. Yet it appears that surveillance is probably more commonly used in Scandinavia than in the United States, where the prevalence of surveillance ranges from 7% to 9%. To my knowledge this is the first report of a nationwide, population based study of men with localized prostate cancer managed by surveillance. Although subtleties in patient characteristics such as tumor volume, and PSA density and velocity were not reported, the results are still reassuring since two-thirds of the men on surveillance remained untreated after 4 years.

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Drug Related Genetic Polymorphisms Affecting Adverse Treatment Reactions in Patients with Urothelial Cancer 

Chemotherapy is currently dosed based on body surface area. Advances in understanding the metabolism of patients given chemotherapy, especially the influence of genetic polymorphisms, promises to allow selective dosing. Therapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) is a standard and widely used regimen for neoadjuvant and adjuvant therapy for urothelial malignancies. Tsuchiya et al (page 2389) from Akita, Japan evaluated 40 patients with urothelial cancer who received MVAC or high dose MVAC. They examined 4 genetic polymorphisms (ABCB1, GSTP1, CYP3A5 and MTHFR) for association with the rate of adverse reactions in the first cycle of MVAC therapy. On multivariate analysis CYP3A5 A6986G phenotype and a lesser number of treatment cycles were independent risk factors associated with leukocytopenia of grade 3 or more. CYP3A5 A6986G phenotype had an odds ratio of 8.2 (95% CI 1.616 to 41.667, p = 0.011) and fewer treatment cycles had an odds ratio of 0.156 (95% CI 0.037 to 0.659, p = 0.011). Thus, the authors conclude that the A6986G polymorphism with CYP3A5, which is involved in the metabolism of vinblastine and doxorubicin, may be a genetic predictor of the severity of leukopenia. Strategies such as this offer hope of reducing adverse side effects while maximizing the therapeutic potential of chemotherapy.

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Robotic Partial Nephrectomy for Renal Hilar Tumors 

Robotic laparoscopic surgery has been increasing in frequency for the treatment of a variety of urological conditions. Rogers et al (page 2353) present a multi-institutional analysis of 11 patients who underwent robotic partial nephrectomy for localized renal hilar tumors. In these select patients mean warm ischemia time was 29 minutes, mean operating time 202 minutes, mean tumor size 3.8 cm, mean blood loss 220 ml and mean hospital stay 3 days. The authors describe the specifics of this technique and propose that for younger, less experienced laparoscopic surgeons, robotic assistance may have value for partial nephrectomy for renal tumors, especially more difficult centrally located tumors.

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Sclerotherapy for Simple Renal Cysts 

Although most patients with simple renal cysts are asymptomatic, some cysts enlarge and cause significant morbidity. In select cases sclerotherapy has been used but the optimal agent and optimal procedure have yet to be elucidated. OK-432 is a mixture of penicillin and a low virulence strain of Streptococcus pyogenes. This agent has been used as sclerotherapy for cystic hygroma and cystic lymphangioma with success in a large numbers of patients. Ham et al (page 2552) from Seoul, Republic of Korea performed a prospective nonrandomized study of 89 patients, of whom 41 received 90% alcohol sclerotherapy at least twice for 50 cysts and 48 received single session OK-432 sclerotherapy for 61 cysts. The protocol is described in detail for serial ethanol injections after aspiration of cyst fluid and replacement of 25% of the cyst volume with 99% ethanol, and for 0.1 mg OK-432 per 20 ml of aspirated cyst fluid. Patients were followed every 3 months for 1 year with ultrasound or computerized tomography, and the outcomes at 1 year are reported.

Overall success rate, defined as the absence of symptoms, complete regression of cysts, or more than 70% reduction in size on serial imaging with no serious side effects, was achieved in 84% of the ethanol group and 98% of the OK-432 group. Although there was no difference in complete resolution of cysts less than 500 cc, complete regression rate in cysts greater than 500 cc was higher in the OK-432 group. Symptom relief in the OK-432 group was also higher than in the ethanol group. Either treatment produced complete regression of cysts smaller than 200 cc. Complication rate was higher in patients receiving ethanol. OK-432 therapy appears to be a reasonable approach with a high success rate, offering the advantages of a single session and possibly great efficacy for larger cysts.

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Clinical and Consumer Trial Performance of SpermCheck Vasectomy 

Pregnancy rates are less than 1 per hundred person-years in couples in whom the male partner has sperm counts less than 1 million per ml. Thus, sperm counts of less than 250,000 per ml seems a reasonable target to achieve for detection of sperm to state whether a patient is “sterile.” Klotz et al (page 2569) from Charlottesville, Virginia take advantage of a protein expressed by human sperm called SP-10 as a biomarker for detection of sperm using monoclonal antibodies. A direct relationship exists between the number of sperm and the signal strength in enzyme linked immunosorbent assay measurements of SP-10 concentrations. The authors used this approach to develop a commercial test patients can take home that is easy and reliable for detecting sperm counts after vasectomy. Compared with hemacytometer counting, SpermCheck Vasectomy had a positive predictive value of 93% and a negative predictive value of 97%. There was 100% agreement between SpermCheck Vasectomy home results and those obtained by laboratory personnel retesting the same semen samples. Two false-positives were observed at sperm concentrations of 235,000 and 245,000 sperm per ml, and 3 false-negatives were observed with sperm concentrations of 296,000, 365,000 and 384,000 sperm per ml. Determination of low sperm counts is inaccurate using a hemacytometer, which brings the method of comparison into question. Nevertheless it appears that SpermCheck Vasectomy is reliable for determining whether patients have low sperm counts and low risk of pregnancy.

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How to Avoid Clean Intermittent Catheterization in Men With Ileal Bladder Substitution 

Incomplete emptying for men with ileal neobladders secondary to obstruction is a common complication. Thurairaja and Studer (page 2504) from Bern, Switzerland outline a methodology for minimizing this complication based on retrospective review of patients who avoided urinary retention and continuous clean intermittent catheterization. The authors stress 1) avoidance of using the funnel-shaped end of the reservoir, 2) ensuring that the pouch sits flat on the pelvic floor to avoid kinking when the bladder is full, and 3) avoiding traction and ensuing damage to the sphincter apparatus by suturing Denonvilliers' fascia. A total of 354 patients with ileal bladder substitution were followed for 5 years, of whom 12% had spontaneous voiding failure at 5 years. Of those surviving 10 years or longer 13% required de-obstructive procedures. The stricture rate using the authors' methodology was 2.2% in the first 5 years and 1.3% in years 5 to 10. Previous reports indicate stricture rates of 2.7% to 8.8%. Most of the obstruction was due to kinking. The authors stress careful attention to technique in the creation of the ileal neobladder to avoid this complication.

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Somatostatin Analogue to Decrease Mucus Production After Enterocystoplasty 

Frequent irrigations and catheter occlusion are not unusual following enterocystoplasty for neurogenic bladder. Khorrami et al (page 2501) from the Islamic Republic of Iran randomized 40 men undergoing enterocystoplasty into antibiotics and antibiotics plus Sandostatin®, a somatostatin analogue. Sandostatin was administered as 0.05 mg every 8 hours subcutaneously beginning 1 hour after the procedure for 15 days after surgery. Mucus production was 4.42 ml in the treatment group vs 42.15 ml in the control group, and irrigations during hospitalization were 0.35 for the treatment group vs 10.35 for the control group. Somatostatin analogue may be a useful adjunct for patients with problematic mucus production after enterocystoplasty.

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Prognostic Factors of Percutaneous Nephrolithotomy Morbidity 

Debate continues regarding morbidity and other outcomes when procedures are restricted to specialized high volume centers vs community or low volume centers. In a retrospective review from a single center de la Rosette et al (page 2489) from Amsterdam, Netherlands examined outcomes after percutaneous nephrolithotomy stratifying patients using the Clavien classification. The study involved 244 procedures divided into pre-2002 (group 1, 68 patients) and post-2002 (group 2, 176 patients) groups, when the institution became a dedicated endourological center. In a multivariate analysis the independent factors in terms of complications were stone size, type of lithotripsy device and whether the specialized center was used. The procedural complication rate was 56.8% in group 1 and 37.2% in group 2. Although this was not a randomized trial and patients were treated at different times, suggesting the potential for a learning curve or changes in technology, the authors infer from these data that treatment at specialized centers results in less operative time, lower complication rates and shorter hospital stays.