Incontinence

REVIEWING THE LITERATURE News and Views from the Literature Prostate Cancer High-Grade Prostatic Intraepithelial Neoplasia on a Prostate Biopsy— What Does It Mean? Reviewed by Alan W. Partin, MD, PhD Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD [Rev Urol. 2002;4(3):157–158] © 2002 MedReviews, LLC nvestigators in the field of urology, oncology, and pathology have been attempting to unravel the mystery of early diagnosis, treatment, and monitoring of men with prostate cancer for several decades. Recently a great deal of attention has been focused on obtaining a better understanding, both pathologically as well as clinically, of the pre-malignant lesion of prostatic intraepithelial neoplasia. Although not diagnostic of prostate cancer on a needle biopsy, many morphologic, molecular, histopathological, I epidemiological, and genetic studies have offered strong evidence that high-grade prostatic intraepithelial neoplasia (HGPIN) is in fact a precursor lesion to development of invasive prostatic adenocarcinoma. Early studies in the literature that first characterized this relationship suggested that histologic evidence of HGPIN on a prostate biopsy predicted a nearly 50% risk of finding prostate cancer on a subsequent prostate biopsy. Through the years, much larger, prospective, population-based studies have suggested that this likelihood is more in the range of 25% to 30%. Knowing that the likelihood of finding prostate cancer after a “negative prostate biopsy" ranges between 10% and 25% if a repeat biopsy were performed brings into question the need or clinical utility of recommending immediate repeat prostate biopsy when HGPIN is seen on initial prostate biopsy. Kronz and associates from the Department of Pathology at the Johns Hopkins Hospital in Baltimore, Maryland have recently published their work investigating how various HGPIN-related factors other than clinical and pathological variables can be used for cancer prediction following an initial diagnosis of HGPIN on a needle biopsy. This important research, published in The American Journal of Surgical Pathology this year, should be required reading for all urologists performing and interpreting the results of prostate needle biopsies within their practice. VOL. 4 NO. 3 2002 REVIEWS IN UROLOGY 157 Urologic Oncology continued Kronz JD, Allan CH, Shaikh AA, Epstein JI. Am J Surg Pathol. 2001;25:1079–1085. Kronz, Epstein, and colleagues questioned the dogma of the need for repeat prostate biopsy following an initial diagnosis of HGPIN. In their retrospective analysis of 245 men in whom the only abnormal finding on the initial prostate biopsy was HGPIN and who had at least one follow-up biopsy, they found that repeat prostate biopsy identified cancer in 32.2% of the men overall. In men in whom only one follow-up biopsy had been performed, only 24.5% of the men were found to have cancer. The only independent histologic predictor of prostate cancer diagnosis on a subsequent biopsy was “the number of cores with HGPIN." The risk of prostate cancer increased as the number of cores found to have HGPIN on the initial biopsy increased. Those men with 1 to 2 cores had a 30% chance of having cancer on a subsequent biopsy, whereas men with 3 or more than 3 cores The only independent histologic predictor of prostate cancer diagnosis on a subsequent biopsy was “the number of cores with HGPIN." with a diagnosis of HGPIN had a 40% and 75% chance of having cancer on a subsequent biopsy, respectively (see Figure 1). Several variables (eg, number of HGPIN glands, maximum percentage of glands involved by HGPIN, nucleolar prominence, percentage of cells with prominent nucleoli, pattern of high HGPIN, digital rectal examination findings, transrectal ultrasound findings, family history of prostate cancer, prostate-specific antigen [PSA] levels at the time of initial prostate biopsy, and the rate of change in serum PSA) demonstrated no predictive value in whether or not a subsequent prostate biopsy would have cancer. The authors conclude that HGPIN does in fact carry with it a clinically significant likelihood of finding cancer in a subsequent prostate biopsy (30% overall), and that with increasing number of cores with HGPIN the likelihood of finding prostate cancer increases (to as much as 75% when more than three cores are found to have this histologic abnormality). They also caution that if cancer is not found on the first two follow-up biopsies after the initial diagnosis of HGPIN, it is unlikely that cancer will be found with subsequent biopsies, and the patient should be followed appropriately with yearly 158 VOL. 4 NO. 3 2002 REVIEWS IN UROLOGY 80 70 Percent Probability Predicting Cancer Following a Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia on Needle Biopsy: Data on Men with More than One Follow-Up Biopsy 60 50 40 30 20 10 0 1 Core All cases 2 Core 3 Core > 3 Cores Cases with multiple biopsies Figure 1. Risk of cancer on subsequent biopsy by number of cores with high-grade prostatic intraepithelial neoplasia. Data from Konz JD, Allen CH, Shaikh AA, Epstein JI. Predicting cancer following a diagnosis of high-grade prostatic intraepithelial neoplasia on needle biopsy. Am J Surg Pathol. 2000;25:1079–1085. exams and PSA testing. Figure 1 graphically demonstrates the likelihood of having prostate cancer on a subsequent biopsy for all cases within this study, as well as those cases in which multiple prostate biopsies were performed after the initial diagnosis of HGPIN. This study highlights the importance of recognizing HGPIN on prostate biopsies and the associated risk of finding adenocarcinoma on subsequent biopsies, which ranges between 30% and 75%, depending on how much HGPIN was seen on the initial biopsy. These results should be analyzed keeping in mind the known false-negative prostate biopsy rates, which can range between 10% and 25%, depending on the number of cores and the biopsy template used. In summary, although the finding of HGPIN places an individual man at a higher risk of having cancer on subsequent biopsy than if the biopsy were benign, the increased risk overall is only 30% and not that much different than the risk of finding prostate cancer on a repeat biopsy if his biopsy were benign (in some studies it is as great as 25%). Additional factors are obviously needed to completely determine if there are subgroups of men with HGPIN who are clearly at a higher risk for subsequent diagnosis of prostate cancer, requiring immediate repeat prostate biopsy. This important study was the first to document that the volume of HGPIN (eg, number of cores involved) carries with it important risk stratification information. If these findings are validated in future prospective and/or multiinstitutional studies, a more rational re-biopsy strategy for men with HGPIN on additional prostate biopsy may be needed. Prostate Cancer Incontinence Antibiotic Prophylaxis for Urodynamics and Estrogen Therapy for Urinary Incontinence Reviewed by Shing-Hwa Lu, MD, PhD, Tracy W. Cannon, MD, Michael B. Chancellor, MD Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA acquired a new UTI after urodynamics. One major and one minor adverse reaction to the antibiotic were reported. The most disappointing section of this study was that the power of the sample size was too small to draw conclusions as to the efficacy of prophylaxis. The study design is good but the early interruption, with suboptimal sample size, constitutes a major limitation. The study did give some idea of the occurrence of infection after urodynamic studies, on the occurrence of asymptomatic The diagnosis of genuine stress incontinence and detrusor instability requires urodynamic evaluation. [Rev Urol. 2002;4(3):159–160] © 2002 MedReviews, LLC hould you give antibiotic prophylaxis for an urodynamic study? Should you prescribe estrogen to treat urinary incontinence and voiding dysfunction? The two articles that we review below will try to shed some light on these two common but difficult questions. S Antibiotic Treatment to Prevent Urinary Tract Infections after Urodynamic Evaluation bacteriuria with a negative dipstick, and on the low incidence of complications after testing, even in patients with untreated bacteriuria. The study also brings attention to the risks of repeat prophylactic antibiotic usage with no proven benefit. Serious anaphylactic reactions and the development of antibiotic resistance should always be considered before the indiscriminate use of antibiotics. At the University of Pittsburgh Urodynamic Laboratory, we generally prophylax with a single pill of antibiotic after the urodynamic evaluation in patients without cardiac risk factors. Peschers UM, Kempf V, Jundt K, et al. Int Urogynecol J. 2001;12:254–257. Should you give antibiotic prophylaxis for an urodynamic study? Urinary tract symptoms, including frequency, urgency, urge incontinence and stress incontinence are common in women. The diagnosis of genuine stress incontinence and detrusor instability requires urodynamic evaluation. Prophylactic administration of antibiotics after urodynamics is used in many institutions to reduce the incidence of de novo urinary tract infection (UTI) after urodynamic testing. The few studies available on the subject could not demonstrate an advantage of routine antibiotic treatment. This study was initiated to determine the efficacy of antibiotic (cotrimoxazole) administration after urodynamic testing to prevent UTI. In a single, blind, prospective, randomized study, 94 women who underwent an urodynamic evaluation were included. All the patients were prescreened to rule out UTI. After multichannel urodynamic testing, including two catheterizations, the women received a single dose of cotrimoxazole or placebo. One week after the urodynamics, a clean-catch urine specimen was tested for UTI. Seventy women returned a urine specimen after 1 week: 2 of 37 (5.4%) in the treatment group and 2 of 33 (6.1%) in the placebo group had The Role of Estrogen Supplementation in Lower Urinary Tract Dysfunction. Hextall A, Cardozo L. Int Urogynecol J. 2001;12:258–261. Should you prescribe estrogen to treat urinary incontinence and voiding dysfunction? The rationale for its use is that estrogen has an important physiological effect on the female lower urinary tract and its deficiency is often an etiological factor in lower urinary tract dysfunction. Urinary symptoms may therefore develop during the menstrual cycle, in pregnancy, and following menopause. Hormone replacement therapy does appear to treat postmenopausal irritative urinary symptoms. A survey of 937 women registered with a rural general practice found the prevalence of incontinence to be most common in the 45–55-year age group, a period which in most cases includes the climacteric. Of 2200 women with mean age of 61 years, 49% had some lower urinary tract VOL. 4 NO. 3 2002 REVIEWS IN UROLOGY 159 Prostate Cancer continued symptoms, and 70% of these patients related the onset of their urinary leakage to their final menstrual period. Estrogen deficiency, particularly when prolonged, is associated with a wide range of urogenital complaints, including frequency, nocturia, incontinence, UTI, and the “urge syndrome." Estrogen supplementation subjectively improves urinary stress incontinence, but there is no objective benefit when given alone; however, estrogen given in combination with phenylpropanolamine may be clinically more useful. This has been reported in the literature but is no longer clinically relevant, as phenylpropanolamine has been shown to be associated with increased risks of cerebral vascular accidents. Therefore phenylpropanolamine is relatively contraindicated for clinical use. Of 166 articles published in English since 1969 on the use of estrogen to treat incontinence, only 6 were reports on controlled trials, and 17 reported on uncontrolled series. The results of a meta-analysis showed that there were significant subjective improvements for all Estrogen supplementation subjectively improves urinary stress incontinence, but there is no objective benefit when given alone. patients and for those with genuine stress incontinence. However, assessment of the objective parameters revealed that there was no change in the volume of urine lost. There is valid clinical evidence accumulated over the past 30 years that hormone replacement therapy does appear to treat postmenopausal irritative urinary symptoms such as frequency and urgency, possibly by reversing urogenital atrophy, and there is also evidence to suggest that estrogens can provide prophylaxis against recurrent UTI. Further studies are required to determine the optimal type of estrogen, route of administration, and duration of therapy. In our practice at the University of Pittsburgh, we generally do not prescribe oral estrogen therapy but would work in conjunction with the patient’s primary physician or the obstetrics/gynecology department when considering hormonal replacement. We do prescribe short courses of topical estrogen therapy preoperatively for stress incontinence and pelvic prolapse surgeries. 160 VOL. 4 NO. 3 2002 REVIEWS IN UROLOGY Prostate Cancer Assessing Quality of Life Following Radiotherapy Reviewed by Herbert Lepor, MD, FACS Department of Urology, New York University School of Medicine, New York, NY [Rev Urol. 2002;4(3):160–161] © 2002 MedReviews, LLC electing a therapy for localized prostate cancer represents a balance between the risks and benefits of the treatment options. The benefits of treatments are the prevention of metastases and increased survival. In the hands of experts, the immediate risks associated with a radical prostatectomy and radiation therapy, which are the accepted treatments for clinically localized prostate cancer, are quite low. The complications that may occur following treatment are related primarily to quality of life issues. It is well recognized that the appropriate methodology for assessing quality of life outcomes following treatment of localized prostate cancer is the use of validated, direct patient questionnaires. One of the deficiencies of the radiotherapy outcomes literature is the lack of long-term assessment of quality of life outcomes using direct patient assessment with standardized assessment tools. S Long-Term Treatment Related Complications of Brachytherapy for Early Prostate Cancer: A Survey of Patients Previously Treated Talcott JA, Clark JA, Stark PC, et al. (J Urol. 2001;166:494-499) Talcott and colleagues reported on the long-term, treatment-related complications of brachytherapy for early prostate cancer. The study included 105 men with at least 2 years, 9 months of follow-up after brachytherapy with or without external beam irradiation. Of these 105 men, 72 underwent seed implantation alone and 33 underwent seed implantation and external beam radiation therapy. Of those men who underwent seed implantation alone, 15% Prostate Cancer indicated that they had fairly frequent diarrhea, passing of mucous per rectum, and/or rectal bleeding following therapy. Such bowel symptoms do not occur following radical prostatectomy. Fifty-five percent of the men undergoing seed implantation alone reported urine leakage; however, only 18% wore an absorptive pad. This result is comparable to the outcome following radical prostatectomy. Only 27% of the men undergoing seed implantation alone had erections firm enough for penetration without manual assistance. In the hands of experts, preservation of sexual function appears to be more likely following radical prostatectomy. The survey did not capture the effect of brachytherapy on lower urinary tract symptoms. The authors attributed the higher-than-expected symptom frequencies to increased reporting by patients with the direct patient survey technique. The direct patient survey technique used by Talcott and associates should become the standard for assessing quality of life complications following radiation therapy. An evidence-based approach should be utilized when counseling men with localized prostate cancer regarding treatment options. This very timely and important paper puts the expectations of brachytherapy into perspective as they relate to quality of life. VOL. 4 NO. 3 2002 REVIEWS IN UROLOGY 161