Survival and secondary interventions following treatment for locally-advanced prostate cancer.

INTRODUCTION: The utility of radical prostatectomy (RP) for locally-advanced prostate cancer remains unknown. Retrospective data has shown equivalent oncologic outcomes compared to radiation therapy (RT). RP may provide local tumor control and prevent secondary interventions from local invasion, and may decrease costs. MATERIALS AND METHODS: Using SEER-Medicare data from 1995-2011 we identified men with locally-advanced prostate cancer undergoing RP or RT. Rates of post-treatment diagnoses and interventions were identified using ICD-9 and CPT codes. Skeletal related events (SRE), androgen deprivation therapy (ADT) utilization, all-cause mortality, prostate cancer-specific mortality, and costs were compared. RESULTS: A total of 8367 men with locally-advanced prostate cancer were identified (6200 RP, 2167 RT). RT was associated with increased urinary obstruction, hematuria, infection, and cystoscopic intervention while RP was associated with increased urethral stricture intervention and erectile dysfunction. Compared to RT, RP was associated with decreased all-cause mortality (3.1 versus 5.2 deaths/100-person-years, p < 0.001), prostate cancer-specific mortality (0.8 versus 2.0 deaths/100-person-years, p < 0.001), SREs (2.0 versus 3.4 events/100 person-years, p < 0.001), and ADT utilization overall (7.4 versus 33.8 doses/100-person-years, p < 0.001) and > 3 years after treatment (3.6 versus 4.6 doses/100-person-years, p < 0.001). Overall and cancer specific costs were significantly lower for RP versus RT. CONCLUSIONS: RT for locally-advanced prostate cancer has a higher incidence of mortality, secondary diagnoses and interventions, SRE, and ADT utilization compared to RP. This may lead to increased costs and have implications for quality of life. Our findings support the utility of RP in appropriately selected men with locally-advanced prostate cancer given the possible decreased morbidity and survival benefit.

Use of surveillance imaging following treatment of small renal masses.

PURPOSE: With the increasing incidence of small renal masses, there is greater use of ablation, nephron sparing surgery and surveillance compared to radical nephrectomy. However, patterns of care in the use of posttreatment imaging remain uncharacterized. The purpose of this study is to determine the rate of posttreatment imaging after various treatments for small renal mass. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology and End Results)-Medicare data during 2005 to 2009, we identified 1,682 subjects diagnosed with small renal mass and treated with open partial nephrectomy (330), minimally invasive partial nephrectomy (160), open radical nephrectomy (404), minimally invasive radical nephrectomy (535), thermal ablation (212) and surveillance (42). Use of imaging was compared within 24 months of treatment and multivariate regression models were constructed to identify factors associated with increased imaging use. RESULTS: On adjusted analyses thermal ablation was associated with almost eightfold greater odds of surveillance imaging compared with open radical nephrectomy (OR 7.7, 95% CI 1.01-59.4). Specifically, thermal ablation was associated with increased computerized tomography (OR 5.28) and magnetic resonance imaging (OR 2.19) use and decreased ultrasound use (OR 0.59). Minimally invasive partial nephrectomy (OR 3.28) and open partial nephrectomy (OR 3.19) were also associated with increased computerized tomography use to a lesser extent. CONCLUSIONS: Subjects undergoing nephron sparing surgery undergo more posttreatment imaging compared to open radical nephrectomy. Although possibly associated with lower morbidity, thermal ablation is associated with significantly greater use of imaging compared to other small renal mass treatments. This may increase costs and radiation exposure, although further study is needed for confirmation.

Outcomes of Robotic Simple Prostatectomy After Prior Failed Endoscopic Treatment of Benign Prostatic Hyperplasia.

Background: We compared outcomes of robot-assisted simple prostatectomy (RASP) in patients with and without a history of prior prostate surgery for management of symptomatic benign prostatic hyperplasia (BPH). Methods: We retrospectively reviewed our multi-institutional database for all consecutive patients who underwent RASP between May 2013 and January 2021. Postoperatively, urinary function was assessed using the American Urological Association symptom score (AUASS) and quality of life (QOL) score. Results: Overall, 520 patients met inclusion criteria. Among the 87 (16.7%) patients who underwent prior prostate surgery, 49 (56.3%), 26 (29.9%), 8 (9.2%), 3 (3.4%), and 1 (1.1%) patients underwent transurethral resection of the prostate, photoselective vaporization of the prostate, transurethral microwave therapy, prostatic urethral lift, or water vapor thermal therapy, respectively. There was no difference in mean prostate volume (p = 0.40), estimated blood loss (p = 0.32), robotic console time (p = 0.86), or major 30-day postoperative (Clavien >2) complications (p = 0.80) between both groups. With regard to urinary function, the mean improvement in preoperative and postoperative AUASS (p = 0.31), QOL scores (p = 0.11), and continence rates was similar between both groups. Conclusion: For management of patients with BPH and lower urinary tract symptoms, RASP is associated with an improvement in urinary function outcomes and a low risk of postoperative complications. Perioperative outcomes of RASP are similar in patients who underwent prior prostate surgery vs those that did not undergo prior prostate surgery.

Alvimopan provides rapid gastrointestinal recovery without nasogastric tube decompression after radical cystectomy and urinary diversion.

INTRODUCTION: Radical cystectomy is associated with significant morbidity, with rates of gastrointestinal complications as high as 30%. Alvimopan is a mu opioid receptor antagonist that has been shown in randomized control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis. We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan. MATERIALS AND METHODS: Between January 2008 and August 2011, 50 consecutive patients underwent radical cystectomy with urinary diversion at our institution. The first 27 patients in our study did not receive alvimopan preoperatively. The latter 23 patients received perioperative alvimopan and were without postoperative nasogastric decompression. Return of bowel function, initiation of diet, and gastrointestinal complications were evaluated. RESULTS: Times to first flatus (3.1 versus 5.6 days, p < 0.001, 95% CI 1.66-3.26) and bowel movement (3.8 versus 6.0 days, p < 0.001, 95% CI 1.35-2.99) were significantly shorter in those patients who received alvimopan. Additionally, the initiation of clear liquid diet (4.1 versus 6.3 days, p < 0.001, 95% CI 1.20-3.12), regular diet (5.7 versus 7.3 days, p = 0.023, 95% CI 0.57-2.63) and hospital discharge (7.4 versus 9.5 days, p = 0.04, 95% CI 0.03-4.21) were accelerated in the alvimopan cohort. There were no incidences of prolonged ileus in patients who received perioperative alvimopan (0% versus 25.9%, p = 0.012). CONCLUSION: In our experience, the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge, eliminates the need for nasogastric tube decompression, and reduces the incidence of postoperative ileus in patients following radical cystectomy and urinary diversion.

The effects of chronic 5-alpha-reductase inhibitor (dutasteride) treatment on rat erectile function.

INTRODUCTION: Numerous clinical series have reported an association between 5-alpha-reductase inhibitors (5ARIs) and sexual dysfunction, but there are limited preclinical data available. AIM: To further investigate the mechanisms of erectile dysfunction (ED) related to 5ARI therapy using a rat model. MAIN OUTCOME MEASURES: Outcome measures include serum dihydrotestosterone (DHT), relaxant and contractile properties of cavernosal muscle, and nitric oxide synthase expression. METHODS: Twenty adult male Sprague-Dawley rats were randomized into control (N = 10) and dutasteride (0.5 mg/rat/day, in drinking water, N = 10) groups. Serum samples were obtained at baseline, from which DHT was measured after 30 days of treatment via radioimmunoassay (Beckman Coulter, Fullerton, CA, USA). Before the terminal blood draw, erectile response was measured using cavernosal nerve stimulation. The relaxant and contractile properties of cavernosal muscle strips were evaluated in tissue baths, and immunohistochemical (IHC) staining for nitric oxide synthase (NOS) and collagen deposition was performed. RESULTS: Mean serum DHT was suppressed by 86.5% (range 64.2-94.8%) after 30 days of 5ARI treatment and was statistically significant (P = 0.0024). In vivo erectile response in the dutasteride treated group decreased significantly compared with control (P < 0.001). While electrical field stimulation (EFS)-induced and acetylcholine-induced relaxation was decreased, EFS-induced and phenlyephrine-induced adrenergic contraction was significantly enhanced in the dutasteride group (P < 0.01). IHC studies demonstrated increased collagen deposition in the treatment arm as well as altered expression of neuronal NOS (nNOS) and inducible NOS (iNOS). CONCLUSIONS: The 5ARIs, as demonstrated in these rat cavernosal smooth muscle studies, have a detrimental effect on erectile function. Enhanced iNOS expression may protect penile smooth muscle from fibrosis. The effect of 5ARIs on human sexual function warrants further investigation.

Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil.

STUDY TYPE: Aetiology (case control) Level of Evidence 3b OBJECTIVE To evaluate the effect of N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)-5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L-NAME induces NO-deficient HT. MATERIALS AND METHODS: Thirty-six adult Sprague-Dawley male rats were divided into three groups, i.e. a control, L-NAME-HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil-treated L-NAME-HT (1.5 mg/rat/day sildenafil, by oral gavage concomitantly with L-NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ-bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: The erectile response was diminished in the HT group. Nitrergic and endothelium-dependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L-NAME-treated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels. CONCLUSIONS: Sildenafil treatment did not correct the ED in L-NAME-treated HT rats. Under sustained high blood pressure, up-regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium-dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT.

Superior mesenteric artery syndrome.

Superior mesenteric artery (SMA) syndrome is defined as compression of the third part of the duodenum secondary to a narrowing of the angle between the SMA and aorta. It is an uncommon disease. We present a patient who suffered from bowel obstruction and eventually perforation of the duodenum and discuss associated imaging findings.

5-alpha reductase inhibitors and erectile dysfunction: the connection.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a common problem affecting middle-aged and elderly men. First-line medical therapy includes alpha 1blockers and 5alpha-reductase inhibitors (5ARIs), such as finasteride and dutasteride. 5ARI use has been associated with adverse sexual outcomes, including erectile dysfunction (ED), ejaculatory dysfunction (EjD), and decreased libido. AIM: To clarify the association between sexual adverse effects (AEs) and 5ARIs through review of literature concerning 5ARIs and to review the proposed mechanisms of these effects. METHODS: A comprehensive literature review, using MEDLINE and PUBMED search engines, was conducted for all publications concerning 5ARIs and sexual AEs. MAIN OUTCOME MEASURE: Sexual adverse effects, such as ED, EjD, and decreased libido, were the measured outcomes of this literature review. RESULTS: Sexual AEs are reported in clinical trials at rates of 2.1% to 38%. The most common sexual AE is ED, followed by EjD and decreased libido. These effects occur early in therapy and attenuate over time. A proposed mechanism for sexual dysfunction involves decreased nitric oxide synthase activity due to decreased dihydrotestosterone. CONCLUSIONS: The connection between 5ARIs and sexual dysfunction is apparent upon review of the literature. Though theories have been proposed, little is known about the exact mechanisms behind 5ARI-related sexual dysfunction. Since the connection between 5ARIs and sexual AEs is established in the literature, future research should be directed toward deciphering the pathophysiologic mechanisms. When more basic science knowledge is attained in this area, the focus can shift toward prevention and treatment.

Prior video game utilization is associated with improved performance on a robotic skills simulator.

Laparoscopic surgery and robotic surgery, two forms of minimally invasive surgery (MIS), have recently experienced a large increase in utilization. Prior studies have shown that video game experience (VGE) may be associated with improved laparoscopic surgery skills; however, similar data supporting a link between VGE and proficiency on a robotic skills simulator (RSS) are lacking. The objective of our study is to determine whether volume or timing of VGE had any impact on RSS performance. Pre-clinical medical students completed a comprehensive questionnaire detailing previous VGE across several time periods. Seventy-five subjects were ultimately evaluated in 11 training exercises on the daVinci Si Skills Simulator. RSS skill was measured by overall score, time to completion, economy of motion, average instrument collision, and improvement in Ring Walk 3 score. Using the nonparametric tests and linear regression, these metrics were analyzed for systematic differences between non-users, light, and heavy video game users based on their volume of use in each of the following four time periods: past 3 months, past year, past 3 years, and high school. Univariate analyses revealed significant differences between heavy and non-users in all five performance metrics. These trends disappeared as the period of VGE went further back. Our study showed a positive association between video game experience and robotic skills simulator performance that is stronger for more recent periods of video game use. The findings may have important implications for the evolution of robotic surgery training.

The role of extended pelvic lymphadenectomy with radical prostatectomy for high-risk prostate cancer.

INTRODUCTION: The role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer (PCa) is controversial. Despite extensive research in both patterns of lymphatic drainage and the clinical effect of lymph node involvement, the exact role of PLND in PCa is yet to be defined. METHODS: A systematic search of the MEDLINE database was performed, and all relevant articles were reviewed in depth. RESULTS: We included 84 relevant articles in our review and subdivided the information into the following categories: preoperative patient evaluation, procedure/extent of dissection, complications, and robotic surgery era. Most authors agree that the greatest benefit is seen in patients with high-risk PCa undergoing RP. Multiple imaging modalities have been evaluated for assistance in patient selection, but the use of preoperative nomograms appears to be the most helpful selection tool. The role of limited PLND vs. extended PLND (e-PLND) is yet to be defined, though many authors agree that e-PLND is preferred in the setting of high-risk PCa. Although PLND is associated with a higher incidence of complications, especially lymphocele formation, it is unclear whether e-PLND leads to more complications than limited PLND. The introduction of minimally invasive surgery may have had a negative effect on implementation of PLND in the appropriate patients undergoing RP. CONCLUSION: Despite a lack of prospective, randomized trials evaluating PLND in RP, there does appear to be a consistent benefit in patients with high-risk disease.

Oncocytic Adrenocortical Neoplasm Diagnosed after Robot-Assisted Adrenalectomy.

Oncocytic tumors, composed of eosinophilic, mitochondria-rich cells, can occur in several locations throughout the body. These tumors can occur in the adrenal cortex and are rarely malignant. We report a case of a patient presenting with an incidental adrenal mass which was later diagnosed as a oncocytic adrenocortical neoplasm (OAN). The patient is a 53-year-old man found to have a 7.2 cm right adrenal mass, incidentally found by computed tomography (CT). After metabolic workup was negative, a right robotic adrenalectomy (RA) was performed. Pathologic analysis revealed clusters of large cells with abundant eosinophilic and granular cytoplasm, consistent with OAN. This pathology is rare, with only about 150 cases described in the literature. It occurs in females 2.5 times more frequently and more commonly on the left side. Diagnosis is usually made by imaging criteria, typically with CT or magnetic resonance imaging (MRI). Treatment is generally surgical, since OAN can be malignant in some cases. Differentiation between benign and malignant OAN is done based on the Lin-Weiss-Bisceglia criteria and can be difficult. If malignancy is diagnosed, recurrence is common and close surveillance should be performed.

Collecting Duct Renal Cell Carcinoma Found to Involve the Collecting System During Partial Nephrectomy: A Case Report.

Collecting duct carcinoma (CDC) is a rare and aggressive form of renal cell carcinoma (RCC) arising from the principal cells of the collecting duct. One third of cases present with metastatic disease, but many present in a manner similar to conventional RCC or urothelial carcinoma (UC). We discuss a case of CDC which presented as a small mass at the cortico-medullary junction, and was discovered at robotic partial nephrectomy (RPN) to be grossly involving the collecting system. A 62-year-old man presented with a small renal mass suspicious for RCC, which was found on computed tomography (CT) after an episode of gross hematuria. After thorough workup, RPN was attempted; however, intraoperatively the mass was found to be involving the collecting system. Radical nephroureterectomy was performed, and the pathology report revealed CDC. CDC is a rare and aggressive form of RCC. While many cases are metastatic at diagnosis, most patients present with the incidental finding of a small renal mass. There are no reports of a CDC involving the collecting system at RPN after negative ureteroscopy preoperatively. The adjuvant therapeutic options for CDC are limited, and long term survival is poor.

Perioperative Outcomes of Robotic and Laparoscopic Simple Prostatectomy: A European-American Multi-institutional Analysis.

BACKGROUND: Laparoscopic and robotic simple prostatectomy (SP) have been introduced with the aim of reducing the morbidity of the standard open technique. OBJECTIVE: To report a large multi-institutional series of minimally invasive SP (MISP). DESIGN, SETTING, AND PARTICIPANTS: Consecutive cases of MISP done for the treatment of bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE) between 2000 and 2014 at 23 participating institutions in the Americas and Europe were included in this retrospective analysis. INTERVENTION: Laparoscopic or robotic SP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographic data and main perioperative outcomes were gathered and analyzed. A multivariable analysis was conducted to identify factors associated with a favorable trifecta outcome, arbitrarily defined as a combination of the following postoperative events: International Prostate Symptom Score <8, maximum flow rate >15ml/s, and no perioperative complications. RESULTS AND LIMITATIONS: Overall, 1330 consecutive cases were analyzed, including 487 robotic (36.6%) and 843 laparoscopic (63.4%) SP cases. Median overall prostate volume was 100ml (range: 89-128). Median estimated blood loss was 200ml (range: 150-300). An intraoperative transfusion was required in 3.5% of cases, an intraoperative complication was recorded in 2.2% of cases, and the conversion rate was 3%. Median length of stay was 4 d (range: 3-5). On pathology, prostate cancer was found in 4% of cases. Overall postoperative complication rate was 10.6%, mostly of low grade. At a median follow-up of 12 mo, a significant improvement was observed for subjective and objective indicators of BOO. Trifecta outcome was not significantly influenced by the type of procedure (robotic vs laparoscopic; p=0.136; odds ratio [OR]: 1.6; 95% confidence interval [CI], 0.8-2.9), whereas operative time (p=0.01; OR: 0.9; 95% CI, 0.9-1.0) and estimated blood loss (p=0.03; OR: 0.9; 95% CI, 0.9-1.0) were the only two significant factors. Retrospective study design, lack of a control arm, and limited follow-up represent major limitations of the present analysis. CONCLUSIONS: This study provides the largest outcome analysis reported for MISP for BOO/BPE. These findings confirm that SP can be safely and effectively performed in a minimally invasive fashion in a variety of healthcare settings in which specific surgical expertise and technology is available. MISP can be considered a viable surgical treatment in cases of large prostatic adenomas. The use of robotic technology for this indication can be considered in centers that have a robotic program in place for other urologic indications. PATIENT SUMMARY: Analysis of a large data set from multiple institutions shows that surgical removal of symptomatic large prostatic adenomas can be carried out with good outcomes by using robot-assisted laparoscopy.

Renal Cell Carcinoma Metastasis from Biopsy Associated Hematoma Disruption during Robotic Partial Nephrectomy.

We describe a case in which a patient with a past medical history of ovarian cancer received a diagnostic renal biopsy for an incidentally discovered renal mass. During left robotic partial nephrectomy (RPN), a perinephric hematoma was encountered. The hematoma was not present on preoperative imaging and was likely a result of the renal biopsy. The renal cell carcinoma (RCC) and the associated hematoma were widely excised with negative surgical margins. On follow-up imaging at five months postoperatively, a recurrent renal mass at the surgical resection bed and several new nodules in the omentum were detected. During completion left robotic total nephrectomy and omental excision, intraoperative frozen sections confirmed metastatic RCC. We believe that a hematoma seeded with RCC formed as a result of the renal biopsy, and subsequent disruption of the hematoma during RPN caused contamination of RCC into the surrounding structures.

Low Grade Micropapillary Urothelial Carcinoma, Does It Exist? - Analysis of Management and Outcomes from the Surveillance, Epidemiology and End Results (SEER) Database.

OBJECTIVE: To elucidate the oncologic behavior of Micropapillary Urothelial Bladder Carcinoma (MPBC), a rare aggressive variant histology. METHODS: All MPBC patients in SEER 17 database were compared with those with traditional urothelial carcinoma (UC). Kaplan-Meier curves were used to determine OS and CSS. A Cox proportional hazards model (CPH) was constructed to test the effect of covariates on outcomes. RESULTS: From 2001-2008, 120 MPBC patients were identified, 0.1% of all bladder cancer. MPBC presented with more high grade (86.1% vs. 38.7%, p<0.0001) and more high stage disease (40.8% NMI vs. 90.4% NMI, p < 0.0001) than UC. Low grade (LG) NMI MPBC had worse OS and CSS compared to LG UC (p=0.0037, p<0.0001 respectively), and did no better than high grade (HG) NMI MPBC. No difference was detected between HG NMI MPBC and HG NMI UC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. UC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 patients underwent definitive therapy, of whom none died of disease. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%). CONCLUSION: Controlling for stage and grade, no survival difference could be detected between MPBC and UC. Low grade NMI MPBC behaved similarly to both high grade MPBC and high grade UC. We propose that all MPBC (regardless of grade) be managed as high grade disease, and that strong consideration for definitive therapy should be given in all cases.

Predictors of Gleason score upgrading in a large African-American population.

PURPOSE: Gleason score from biopsy specimens is important for prostate cancer (PCa) risk stratification and influences treatment decisions. Gleason score upgrading (GSU) between biopsy and surgical pathology specimens has been reported as high as 50 % and presents a challenge in counseling low-risk patients. While recent studies have investigated predictors of GSU, populations in these studies have been largely Caucasian. We report our analysis of predictors of GSU in a large urban African-American population. METHODS: A total of 959 patients with D'Amico low-risk prostate cancer underwent radical prostatectomy at Georgetown University or Washington Hospital Center between January 2005 and July 2012. Race, age, PSA, body mass index (BMI), cancer of the prostate risk assessment (CAPRA) score, and transrectal ultrasound (TRUS) biopsy characteristics (percent of biopsy cores showing adenocarcinoma, highest percent of biopsy core involved with cancer, and measured TRUS prostate volume) were analyzed with both univariate and multivariate analyses to identify significant predictors of GSU while controlling for clinical parameters. RESULTS: Of the 959 cases, 288 (30.0 %) were upgraded on final pathologic specimen with approximately 38 % (133/355) of African-American patients experiencing GSU. BMI (P = 0.02), percent positive biopsy cores (P < 0.01) and percent of core involved with cancer (P < 0.01), increasing CAPRA score, and serum PSA were independent predictors of GSU on both uni- and multivariate regression analyses. African Americans had a 73 % increase in the incidence of GSU over other races. CONCLUSION: More than a quarter of low-risk prostate cancer patients were upgraded on final pathology in our series. Higher BMI, serum PSA, CAPRA score, percent of cores positive, and percent of cores involved were independent predictors of GSU. Individuals with those clinical parameters may harbor occult high-grade disease and should be carefully counseled on treatment decisions.