The Journal of Urology
Volume 181, Issue 3 , Pages 935-937, March 2009

This Month in Adult Urology

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Adjuvant Radiotherapy for Prostate Cancer Reduces Risk of Metastases and Improves Survival 

This landmark multi-institutional study by Thompson et al (page 956) provides extremely useful information on the treatment of patients after radical prostatectomy. For most clinicians the most common strategy for extraprostatic disease and detectable postoperative prostate specific antigen (PSA) is to monitor the PSA and initiate therapy at the time of biochemical recurrence. In this study immediate adjunctive therapy (214) was compared to radiation therapy at the time of disease recurrence after PSA failure (211) in 425 men with pT3N0M0 disease. Metastasis-free survival was significantly higher in the men treated with adjuvant radiation at the time of surgery. While earlier data suggested that biochemical failure was reduced, this study revealed improved survival with a median 1.7-year survival benefit. This survival benefit may apply to more than 30,000 men per year in the United States. To put this in perspective, the authors note that improved survival with docetaxel, the only treatment proven to improve survival, is only 1.9 to 2.3 months. This information should be shared with patients in an effort to help counsel them about the role of radiation therapy, especially if pT3 disease is detected in the surgical specimen.

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New Vision for the Study of Benign Prostate Disease 

Benign prostatic hyperplasia and chronic prostatitis/chronic pelvic pain syndrome are common urological conditions affecting men, which cause tremendous morbidity and loss of productivity, and account for several billion dollars in annual health care costs. Yet many complex and unresolved issues regarding the development and treatment of these conditions mandate a need to better define the cellular pathology, and translate laboratory and clinical findings into the development of improved therapies.

The National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) organized a prostate research planning committee composed of thought leaders in basic and clinical sciences and epidemiology to define current deficits in the understanding and management of these disorders. According to Mullins from the NIDDK and Kaplan from New York (page 963) the NIDDK Prostate Research Strategic Plan was the product of multiple meetings over several years. High priorities for basic research included the creation of new models of disease, a better understanding of the signal transduction and cellular communication in the prostate, development of targeted therapies, application of new technological and imaging modalities to study disease, and examination of the consequences of aging. Epidemiological directives highlighted the need for better classifications and definitions, data and tissue resources, and clinical trials. Translational imperatives focused on investigation of the relationship of histological changes and disease in addition to identification of biomarkers. Overreaching goals included better data dissemination and training, and multidisciplinary team research.

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Intravesical Mycobacterial Cell Wall-DNA Complex for Carcinoma In Situ of the Bladder 

It has been recognized that mycobacterial cell wall extract, which is a cell wall composition from Mycobacterium phlei, has anticancer activity and demonstrates efficacy in 30% to 40% of patients in whom bacillus-Calmette Guerin (BCG) fails. A previous mycobacterial cell wall extract emulsion contained thimerosal, an organomercurial preservative known to be associated with adverse events. Morales et al (page 1040) from Kingston, Ontario, Canada assessed the clinical efficacy of a replacement mycobacterial cell wall DNA complex (MCC) which does not contain thimerosal and showed promising results. A total of 55 men received 4 or 8 mg doses of MCC after previous treatment with BCG. The complete response rate was 27.3% in the 4 mg group at 12 and 26 weeks and 46.4% in the 8 mg group at the same time points. The nonresponders tolerated the doses well. Thus, MCC has shown antineoplastic activity in patients with less toxicity than that associated with BCG. MCC seems promising for the treatment of carcinoma in situ of the bladder.

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Urinary Tract Infections Among Women With Type 1 Diabetes Mellitus 

Debate continues whether diabetic women are at a higher risk for urinary tract infections than nondiabetic females. In a multi-institutional study Czaja et al (page 1129) analyzed data from the EDIC (Epidemiology of Diabetes Interventions and Complications) study cohort to compare the prevalence of cystitis with a nondiabetic subset of female participants in the NHANES III (National Health and Nutrition Examination Survey III). Most studies have shown that type 2 diabetes is associated with a higher risk of urinary infections with more virulent organisms or more complicated infections. The current study of 550 women with type 1 diabetes showed a prevalence of cystitis and pyelonephritis during the preceding 12 months of 15% and 3%, respectively. The adjusted prevalence of cystitis among the women in the EDIC study was 19.1% compared to 23.1% of those in the NHANES III group, indicating no significant difference. Pyelonephritis was too rare an event to analyze. The authors conclude that the prevalence of cystitis in diabetic and nondiabetic women was similar. It remains to be shown whether the prevalence of upper urinary tract infection is higher in this population.

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Oral Thalidomide vs Placebo for Androgen Dependent Prostate Cancer 

The search continues for nonhormone based therapies for patients with advanced prostate cancer. Figg et al (page 1104) examined 159 patients in a multi-institutional double-blind randomized trial to determine if thalidomide can improve the efficacy of gonadotropin receptor hormone agonist (GnRH-A) therapy in hormone responsive patients with increasing PSA after primary definitive therapy for prostate cancer. Patients were randomized to 6 months of GnRH-A followed by 200 mg thalidomide a day or placebo. At the time of PSA progression GnRH-A was restarted for an additional 6 months. Patients were then crossed over and treated until PSA progression. The median time to progression for the thalidomide group was 17.1 months vs 6.6 months with placebo. The authors indicate that thalidomide in patients placed simultaneously on GnRH agonist did not render any benefit. However, when disease becomes hormone refractory it appears that thalidomide has an added benefit. To my knowledge this is the first study to demonstrate that thalidomide used intermittently with hormone therapy has promise for adoption into the wider population.

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Nomograms for Predicting Graft Function and Survival in Living Donor Kidney Transplantation 

Tiong et al (page 1248) from Cleveland, Ohio designed 3 nomograms to predict 1-year glomerular filtration rate (GFR) and 5-year graft survival after living donor kidney transplantation. The first nomogram predicts GFR based on donor and recipient information known at the time of surgery. The second nomogram predicts 5-year graft survival using the same information. A third nomogram predicts 5-year survival based on additional information that becomes available 6 months after transplantation. The authors demonstrated that these nomograms based on the UNOS (United Network for Organ Sharing) registry were validated for predicting 1-year GFR and 5-year survival. While the predictive value of first year GFR (r2 =0.13) was of modest value this set of nomograms may be useful. The authors illustrate their usefulness with a hypothetical case for patient counseling, especially for selecting between 2 different donors. They warn that there is a potential for abuse of these nomograms by encouraging patients to shop around for the best possible donor.

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How Useful and Realistic is the Virtual Reality Simulator 

The search is continuing for the best way to train surgeons using virtual devices to avoid animal vivisection similar to those used in other technical industries. In this study by Schout et al (page 1297) from the Netherlands 104 urologists and urology residents performed transurethral resection of the prostate and transurethral resection of a bladder tumor on the Storz Uro Trainer, and rated its usefulness and realism using a 10-point scale. Measured against criteria from other validation studies, the face and content validity of this simulator appear to be unsatisfactory. The authors recommend modification of the simulator before other validation studies are begun. While novice performers rated the Uro trainer more highly, experienced surgeons questioned its usefulness.

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A Scoring System to Improve the Selection of Upper Ureteral Stones for Shock Wave Lithotripsy 

Ng et al (page 1151) from Hong Kong recruited 94 patients for a study using non-contrast computerized tomography (CT) scans to predict outcomes of shock wave lithotripsy. Logistic progression showed that stone volume, stone density and skin-to-stone distance were potential predictors. From receiver operator curves (ROC) the optimum cut-off points for predicting treatment outcomes for stone volume, stone density and skin-to-stone distance were 0.2 cc, 593 HU and 9.2 cm, respectively. A simple scoring system was developed to correlate the stone-free rate for patients having 0, 1, 2 or 3 factors as 17.9%, 48.4%, 73.3% and 100%, respectively, using linear-bilinear association testing. A scoring system such as this could be useful in advising patients of relative stone-free rates. However, the study was performed in a small number of patients and these data need to be confirmed by a larger multi-institutional trial.

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The Number of Positive Cores on Initial Biopsy is Associated With Prostate Cancer on Second Biopsy 

Controversy exists whether high grade prostatic intraepithelial neoplasia (HGPIN) is premalignant and whether its presence mandates repeat prostate biopsy. Previous studies suggest there might be some predictive value in HGPIN but these studies were based on 6-core biopsies. Therefore, with the standard 12-core biopsy there is some question whether this is still useful. De Nunzio et al (page 1069) from Rome, Italy evaluated 650 patients with increased PSA or abnormal digital rectal examination of whom 147 (22%) had HGPIN. Of the 147 patients 19% with HGPIN on first biopsy had prostate cancer on second biopsy. Gleason score was 6 in 14 patients, 7 in 7 and 8 in 1. The presence of HGPIN on 4 or more cores in the first biopsy was significantly associated with prostate cancer on second biopsy. While this seems to indicate the usefulness of repeat biopsy, the limitations of this study include the small number of patients and the 6-month interval between biopsies. Perhaps using the 12-core biopsy, repeat biopsy may not be necessary.

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Outcome Analysis of Urethral Wall Stent Insertion With Artificial Urinary Sphincter Placement 

Magera et al (page 1236) from Rochester, Minnesota reviewed the quality of life in a series of 25 consecutive men who underwent urethral wall stent (UWS) placement for severe bladder neck contracture after radical prostatectomy despite previous aggressive transurethral resections. Before UWS stress incontinence was present in 92% of the patients. Contracture stabilization occurred in 52% with insertion of 1 UWS. Another 24% of cases were salvaged by additional UWS insertions and 24% failed to obtain patency. Several patients suffered severe morbidity including subsequent renewal of the contracture and osteomyelitis. While the authors have shown that UWS improved quality of life for most patients, counseling is needed regarding the potential for serious morbidity and the necessity for multiple UWS insertions. A technical video accompanies this article.

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Modified York-Mason Technique for Iatrogenic Rectourinary Fistula 

Rectourinary fistula (RUF) is a devastating complication after radical retropubic prostatectomy or focal therapies. Kasraeian et al (page 1178) from Paris, France reviewed the records of 12 patients who underwent a RUF repair using a modified York-Mason technique at their institution. The 2 o'clock rather than the 9 o'clock position was used to avoid resection of the coccyx. RUF developed after radical prostatectomy in 10 cases and after high frequency focused ultrasound in 2. Six patients were initially treated with fecal diversion. After a median followup of 22 months the fistula completely resolved in all 12 patients, although 3 patients required multiple York-Mason procedures to achieve complete resolution. All patients reported fecal continence. The authors conclude that the York-Mason procedure offers a simple, safe and effective approach to repair of small, iatrogenic RUF.

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Natural History of Residual Fragments After Percutaneous Nephrostolithotomy 

Raman et al (page 1163) from Dallas, Texas report on 728 patients who underwent percutaneous nephrostolithotomy at a single medical center. Of these patients 42 (8%) had a documented residual fragment and were followed for at least 6 months. The primary study end point was a stone related event involving growth of the fragment or an emergency room visit. Of the 42 patients 18 (43%) experienced a stone related event at a median of 32 months after nephrostolithotomy. Only stone size larger than 2 mm, or location in the renal pelvis or ureter independently predicted a stone event on univariate analysis. Thus, larger fragments and fragments retained in the pelvis or ureter are more likely to require intervention.

PII: S0022-5347(08)03346-6

doi:10.1016/j.juro.2008.12.024

The Journal of Urology
Volume 181, Issue 3 , Pages 935-937, March 2009

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