This Month in Clinical Urology

Article Outline

• Salvage Cryoablation of the Prostate
• Botulinum Toxin A for Idiopathic Detrusor Overactivity
• Gunshot Wound Injuries of the Prostate and Posterior Urethra
• Plasminogen Activation Inhibitor Type 1 Improves Predictive Accuracy of Prostate Cancer Nomograms
• Vitamin E and Propionyl-L-Carnitine for Early Chronic Peyronie’s Disease
• The Silence of the Stones
• Preoperative Testing and Outcomes of Sling Surgery for Incontinence
• Topical Antimicrobial Scrub and Positive Culture Rates Associated With Artificial Urinary Sphincter Placement
• Survival of Patients With Lymph Node Metastasis Treated With Surgery Only
• Positive Surgical Margin in Areas of Capsular Incision at Radical Prostatectomy
• Book Reviews
• Copyright

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Salvage Cryoablation of the Prostate 

Prostate cancer recurs locally in about a third of patients treated with radiation therapy, and there is no agreement on the optimal management of local recurrence. Treatment options with curative intent include salvage prostatectomy, brachytherapy and cryoablation. Ng et al (page 1253) from Ontario, Canada offer cryoablation as a minimally invasive treatment option, and assess the short and intermediate term efficacy of the procedure with an emphasis on finding predictive factors that will lead to improved outcome.

Cryotherapy of the prostate was performed in 187 patients with locally recurrent prostate cancer after radiotherapy. Mean followup was 39 months. Variables tested included serum prostate specific antigen (PSA) before radiation therapy, serum PSA at cryoablation, clinical stage before radiation therapy, Gleason score before radiation therapy, Gleason score at cryoablation, number of positive biopsy cores and use of neoadjuvant hormonal therapy before cryoablation. The authors observed that serum PSA at cryoablation was a predictive factor for biochemical recurrence (BCR) on univariate and multivariate analyses. Patients with pre-cryoablation PSA less than 4 ng/ml had a 5 and 8-year BCR-free survival of 56% and 37%, respectively, in contrast to patients with pre-cryoablation PSA 10 ng/ml or greater who had a 5 and 8-year BCR-free survival of only 14% and 7%, respectively. Overall 5 and 8-year survival was 97% and 92%, respectively. The authors conclude that salvage cryotherapy is a viable treatment option for patients with prostate cancer in whom radiation therapy failed, and that salvage cryoablation should be performed when serum PSA is relatively low.

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Botulinum Toxin A for Idiopathic Detrusor Overactivity 

Botulinum toxin A (BTX-A) has been shown to have therapeutic effects on detrusor overactivity of neurogenic or idiopathic etiology. It inhibits the release of acetylcholine from presynaptic nerve fibers resulting in paralysis of the adjacent muscle fibers. BTX-A injection can paralyze and reduce detrusor muscle contractility, which explains its effectiveness as a treatment of neurogenic or idiopathic detrusor overactivity (IDO). Inhibition of neurotransmitters in the suburothelial afferent fibers may have a beneficial therapeutic effect in patients with sensory urgency and idiopathic detrusor overactivity.

Kuo (page 1359) from Hualien, Taiwan assessed 45 patients with IDO refractory to antimuscarinic therapy who were randomly allocated to receive 100 U BTX-A injected into the detrusor, suburothelial or bladder base. Data collected included symptom score, urgency and incontinence episodes, and urgency severity score. A total of 15 patients were allocated to each treatment group, and a successful result at 3 months was achieved in 93% with detrusor, 80% with suburothelial and 67% with bladder base injection. The success rate in the detrusor, suburothelial and bladder base injection groups decreased with time to 67%, 47% and 13% by 6 months, and 20%, 20% and 6.7% at 9 months, respectively. Vesicoureteral reflux was not found in any patient after BTX-A injection. Urgency severity scores improved significantly in all groups. At 3 months after treatment significant increases in cystometric capacity and post-void residual compared to baseline were found in the detrusor and suburothelial but not in the bladder base group. In conclusion, intravesical injection of 100 U BTX-A by all 3 methods had a therapeutic effect on IDO. Bladder base BTX-A injection relieved urgency sensation but did not increase bladder capacity.

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Gunshot Wound Injuries of the Prostate and Posterior Urethra 

Anterior urethral involvement has been reported in 17% to 22% of male genital gunshot wounds. Tausch et al (page 1346) from Fort Sam Houston, Texas report on a multi-institutional experience with posterior urethral gunshot wound injuries, and describe the various management options and long-term outcomes. Records were retrospectively reviewed of 19 men who sustained posterior urethral gunshot wounds confirmed by retrograde urethrography and/or exploratory laparotomy. Treatment options included immediate primary repair in 2 cases, delayed reconstruction in 15 and complete prostatectomy in 2. Of the 15 patients who underwent delayed repair 86.6% demonstrated normal flow rates and lack of lower urinary tract symptoms. The 2 remaining patients experienced obliterative stricture recurrence and were treated with open surgery. Both patients who underwent immediate primary repair had normal flow rates. Of the 2 men who underwent immediate prostatectomy 1 had moderate incontinence that required absorbent pad use and the other was lost to followup. An initial management strategy based on the principles of maximizing urethral catheter drainage, with direct retropubic/urethral realignment when possible and definitive perineal reconstruction when necessary, appears to provide acceptable outcomes while minimizing the number of subsequent interventions required.

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Plasminogen Activation Inhibitor Type 1 Improves Predictive Accuracy of Prostate Cancer Nomograms 

Cancer invasion and metastasis are complex processes in which degradation of the extracellular matrix has a crucial role. This degradation is accomplished by the concerted action of several enzyme systems including generation of the serine protease plasmin by the urokinase plasminogen activator (uPA). The uPA axis has a central role in cancer invasion and metastasis, cell proliferation, chemotaxis and angiogenesis. The enzymatic activity of uPA can be rapidly neutralized by its high affinity inhibitors, PAI-1 and PAI-2. In prostate cancer increased levels of uPA family members are associated with tumor invasion and osteoblastic metastases. While circulating levels of PAI-1 have been associated with poor prognosis in several cancer models, they have not been tested in prostate cancer.

Shariat et al (page 1229) from Dallas, Texas tested whether the addition of preoperative circulating PAI-1 levels could improve the accuracy of the standard preoperative and postoperative models for the prediction of BCR in patients treated with radical prostatectomy for clinically localized disease. Preoperative PAI-1 levels were measured in 429 consecutive patients undergoing radical prostatectomy for clinically localized disease. Patients were randomly divided into a development (67%) and a split sample validation cohort (33%). In a standard univariate analysis categorically coded preoperative PAI-1 was significantly associated with BCR, and in standard preoperative and postoperative multivariate analyses preoperative PAI-1 was independently associated with BCR. In the split sample validation cohort the addition of PAI-1 increased the predictive accuracy of the preoperative multivariate model as well as the postoperative model. Preoperative circulating PAI-1 is a predictor of BCR, and enhances the accuracy of preoperative and postoperative nomograms. The nomograms may assist in clinical decisions regarding treatment choice and followup, as well as identification of patients at high risk for BCR who may benefit from neoadjuvant and/or adjuvant treatment.

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Vitamin E and Propionyl-L-Carnitine for Early Chronic Peyronie’s Disease 

Peyronie’s disease (PD) is characterized by a fibrotic plaque of the tunica albuginea which in the majority of cases involves the dorsal part of the corpus cavernosum. Many oral medications have been reported as having limited success in treating this disorder, including vitamin E, potassium aminobenzoate, tamoxifen, colchicines, orgotein, procarbazine, systemic steroids and nonspecific antihistamines. In addition to other local treatments, intralesional therapy has also been described. Previous studies have shown that the combination of propionyl-L-carnitine (PLC) and verapamil has been considered for the treatment of advanced and resistant PD. Therefore, Safarinejad et al (page 1398) from Tehran, Iran compared the efficacy and safety of oral vitamin E and/or PLC for Peyronie’s disease.

A total of 236 men with Peyronie’s disease were assigned to 4 treatment groups: group 1—300 mg vitamin E twice daily, group 2—1 gm PLC twice daily, group 3—300 mg vitamin E and 1 gm PLC orally twice daily and group 4—similar regimen of placebo. The efficacy of the 4 treatments was assessed using responses to the International Index of Erectile Function, visual analog scale for pain evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes, penile curvature, plaque size and adverse drug effects. Of the patients in groups 1 to 4 pain decreased in 60.4%, 63%, 62.3% and 59.2%; penile curvature reduction was observed in 18.9%, 20.4%, 22.6% and 18.4%; and plaque size decreased in 11.3%, 12.9%, 13.2% and 11.1%, respectively. The authors conclude that there was no significant improvement in pain, curvature or plaque size in patients with PD treated with vitamin E, PLC or vitamin E plus PLC compared to those treated with placebo.

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The Silence of the Stones 

The prevalence of nephrolithiasis is 5% to 10% in Europe and North America, and ureteral stones typically present with acute renal and ureteral colic as a result of a stone obstructing the urinary tract or during stone passage. Silent ureteral calculi have only been observed in patients with residual fragments following primary extracorporeal shock wave lithotripsy or ureteroscopy, and those on surveillance and renal function monitoring for primarily symptomatic ureteral stones. Wimpissinger et al (page 1341) from Vienna, Austria prospectively studied patients primarily presenting with asymptomatic calculi in the ureter during a 12-year period. The main objective of the study was to evaluate the mode of diagnosis of silent ureteral calculi. A total of 40 patients with asymptomatic ureteral stones were identified during this period among 3,711 patients with ureteral stones (1.1%). Mean patient age of the 33 males and 7 females was 58.3 years and the location of the stones was proximal in 19, mid in 3 and distal ureter in 18. Mean stone size was 10.0 mm. Stones were diagnosed by the presence of hydronephrosis in 10 patients (25%), microscopic hematuria in 8 (20%), randomly on other than urological examinations in 13 (32.5%) and during followup after previous nephrolithiasis in 9 (22.5%). Primary therapy was extracorporeal shock wave lithotripsy in 35 patients and ureterorenoscopic lithotripsy in 4 while 1 patient passed the stones spontaneously. (CME credit article)

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Preoperative Testing and Outcomes of Sling Surgery for Incontinence 

Slings, along with the Burch procedure, are considered by many the gold standard in the surgical treatment of female stress urinary incontinence. However, data on complication rates after sling surgery have historically been derived from retrospective studies of clinical subjects with a large focus on continence outcomes and surgical complications. To date, little is known of the effect of preoperative testing, specifically urodynamics and cystoscopy, on patient outcomes. In 1996 the Agency for Healthcare Policy and Research updated guidelines for evaluating stress incontinence in women, and it was recommended that those with uncomplicated stress incontinence undergo a detailed history and physical examination, urinalysis, provocative stress test and measurement of post-void residual urine volume. Urodynamic testing was only recommended in patients with complicated factors and comorbidities.

Because of concern that inaccurate diagnoses may be made in women who do not undergo urodynamics, resulting in inappropriate treatment in up to a third with stress incontinence symptoms, Anger et al (page 1364) from Los Angeles, California analyzed 1999 to 2001 Medicare claims data and a 5% national random sample of beneficiaries. Women who underwent sling procedures between July 1, 1999 and December 31, 2000 were identified on the basis of the presence of CPT-4 code 57288 (sling operation for stress incontinence). Subjects were tracked for 6 months before surgery to identify the type of preoperative studies performed and for 12 months after surgery to assess short-term complications. Patients who underwent preoperative urodynamic study were more likely to be newly diagnosed with urge incontinence after surgery and those who underwent preoperative cystoscopy were significantly more likely to be diagnosed with or treated for outlet obstruction postoperatively than those who did not. Multivariate analysis revealed that patients who underwent preoperative urodynamics were significantly less likely to undergo postoperative urodynamics than those who did not. The authors conclude that the findings of worse outcomes in women who underwent preoperative testing may be due, in part, to case selection. Women who underwent preoperative urodynamics were only a third as likely to undergo postoperative urodynamics as those who did not support preoperative urodynamics. However, the true effect of urodynamics on sling outcomes remains controversial. (CME credit article)

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Topical Antimicrobial Scrub and Positive Culture Rates Associated With Artificial Urinary Sphincter Placement 

Artificial urinary sphincter (AUS) implantation is an effective and durable treatment for intrinsic sphincter deficiency following radical prostatectomy and transurethral resection of the prostate. One of the most significant complications of AUS implantation is infection, typically requiring explantation and delayed reimplantation. The use of chlorhexidine gluconate for surgical hand scrubs has been shown to produce a log scale reduction in quantity of cutaneous bacteria. Residual antimicrobial activity is noted with chlorhexidine, which further reduces microbial counts when applied for 5 days. Magera et al (page 1328) from Rochester, Minnesota prospectively studied the ability of a 5-day topical chlorhexidine scrub to suppress abdominal and perineal cutaneous bacteria in 100 consecutive AUS implants between May 2003 and November 2005. Comparisons were made between 50 men who performed preoperative topical antimicrobial scrub (TAS) with 4% chlorhexidine to the abdominal and perineal sites and 50 men who used normal hygiene (soap and water). All men received povidone-iodine skin disinfection before incision. Bacterial cultures of the abdominal and perineal sites were collected immediately after skin disinfection and after AUS implantation. Overall 140 of the 400 cultures were positive with only 37% of the positive cultures observed with TAS. For the perineal site the only factor affecting preoperative culture status was TAS, and a positive postoperative culture was predicted by a positive preoperative perineal and abdominal culture. Preoperative TAS resulted in a 4-fold reduction in the preoperative perineal colonization rate and overall reduction in positive surgical site cultures. Given the low cost, safety and efficacy, TAS should be considered before AUS placement. (CME credit article)

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Survival of Patients With Lymph Node Metastasis Treated With Surgery Only 

Early studies report 16% to 33% long-term survival for patients with 1 or 2 microscopic pelvic lymph node metastases after radical cystectomy and extended pelvic lymph node dissection to the distal aorta for bladder cancer. More recently radical cystectomy with extended pelvic lymph node dissection was reported to improve survival by 21% compared to standard lymphadenectomy for patients with bladder cancer confined to the bladder wall. To assess the role of extended lymphadenectomy Steven and Poulsen (page 1218) from Herlev, Denmark report the survival of patients after radical cystectomy with lymph node involvement above the bifurcation of the common iliac vessels treated with surgery alone. Between 1993 and June 2005 a total of 336 consecutive patients underwent radical cystectomy and pelvic lymphadenectomy without preoperative or postoperative chemotherapy. Pelvic lymph node dissection began at the distal aorta, including the common and external iliac lymph nodes, and the periaortic, presacral and obturator fossa nodes.

The 5-year overall and recurrence-free survival rates in the entire study population were 68% and 69%, respectively. Overall 19% of patients had lymph node metastases of whom 34.4% had lymph node involvement above the bifurcation of the common iliac vessels outside the template of the standard lymph node dissection. Lymph node involvement proved a significant adverse prognostic factor with a 5-year probability of survival of 39% vs 76%. The overall 5-year survival rates were similar in patients with lymph node involvement above the bifurcation of the common iliac vessels (37%) compared to the entire population with lymph node metastasis (41%) and to those with lymphatic metastases in the true pelvis below the bifurcation of the common iliac vessels (42%). The survival rate was significantly higher in patients with 5 or less involved lymph nodes (50% vs 13%) and in those with lymph node density less than 20% (25% vs 47%) but it did not relate to the total number of retrieved lymph nodes. Overall 34% of patients with lymph node metastases had nodal involvement in the common iliac, periaortic and presacral regions, and extended dissection not only provided the most accurate staging but also offered the best chance of survival. The authors support the contention that the benchmark for radical cystectomy is extended pelvic lymph node dissection with anatomical boundaries including the common iliac and presacral nodes. (CME credit article)

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Positive Surgical Margin in Areas of Capsular Incision at Radical Prostatectomy 

The controversy surrounding the importance of capsular incision in men with organ confined disease has been brought into focus with the increased interest in less invasive approaches to radical prostatectomy. However, when the majority of men have organ confined disease, failure to remove all of the tumor may occur when there is iatrogenic incision into tumor that is confined to the prostate. Chuang et al (page 1306) from Baltimore, Maryland investigated the impact of capsular incision into cancer on biochemical-free survival. Inclusion criteria were positive margin in an area of capsular incision, no extraprostatic extension (EPE), negative seminal vesicles and lymph nodes, entire prostate submitted for examination and no neoadjuvant therapy. Postoperative progression in 135 cases of radical prostatectomy with capsular incision (1.3% of radical prostatectomies from 1993 to 2004) was compared to that of 10,311 radical prostatectomies without capsular incision. Mean tumor length at the incision was 2.6 mm, and the incision was posterolateral in 61.5% of cases, posterior in 18.5%, anterior in 8.9%, lateral in 8.1% and apical in 3%.

The 5-year actuarial freedom from BCR for tumors with capsular incision was worse (71.3%) than organ confined, margin negative tumors (96.7%) and focal EPE margin negative disease (89.7%), yet better than that of extensive EPE margin positive tumors (58.5%). The risks of progression for men with capsular incision, focal EPE margin positive and extensive EPE margin negative disease were not statistically different. The 5-year risks of biochemical progression were 20.0% and 55% for less than 3 mm and 3 mm or more of tumor cut, respectively. Isolated capsular incision into tumor is uncommon in radical prostatectomy. However, isolated capsular incision has a higher recurrence rate than organ confined or focal extraprostatic extension margin negative disease, yet a lower recurrence rate than extensive EPE margin positive tumor, and a worse prognosis with greater extent of capsular incision. (CME credit article)

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Book Reviews 

On page 1555 Schellhammer reviews Surviving Prostate Cancer and on page 1554 Siegel reviews Abdominal-Pelvic MRI, 2nd ed.