The "Minimal-Touch" Technique for Artificial Urinary Sphincter Placement: Description and Outcomes.

OBJECTIVE: The study aimed to describe "minimal-touch" technique for primary artificial urinary sphincter placement and evaluate early device outcomes by comparing it with a historical cohort. MATERIALS AND METHODS: We identified patients who underwent primary artificial urinary sphincter placement at our institution from 1983 to 2020. Statistical analysis was performed to identify the rate of postoperative device infection in patients who underwent minimal touch versus those who underwent our traditional technique. RESULTS: 526/2601 total procedures (20%) were performed using our "minimal-touch" approach, including 271/1554 patients (17%) who underwent primary artificial urinary sphincter placement over the study period. Around 2.3% of patients experienced device infection after artificial urinary sphincter procedures. In the "minimal-touch" era, 3/526 patients (0.7%) experienced device infection, including 1/271 (0.4%) of those with primary artificial urinary sphincter placement. In comparison, 46/2075 patients (2.7%) experienced device infection using the historical approach, with 29/1283 (2.3%) of primary artificial urinary sphincter placements resulting in removal for infection. Notably, 90% of device infections occurred within the first 6 months after primary placement. The difference in cumulative incidence of device infections at 12 months did not meet our threshold for statistical significance for either the total cohort of all AUS procedures (primary and revision) or the sub-group of only those patients undergoing primary artificial urinary sphincter placement (Gray K-sample test; P=.13 and .21, respectively). CONCLUSION: The "minimal-touch" approach for artificial urinary sphincter placement represents an easy-to-implement modification with potential implications on device outcomes. While early results appear promising, longer-term follow-up with greater statistical power is needed to determine whether this approach will lower the infection risk.

Relative impact of lymph-node metastasis and seminal vesical invasion on oncologic outcomes following radical prostatectomy.

BACKGROUND: While both seminal vesicle (SVI) and lymph-node invasion (LNI) have been identified as adverse prognostic variables among men undergoing radical prostatectomy (RP), the relative impact of each of these features on subsequent oncologic outcomes has not been well defined. We assessed the impact of LNI on long-term oncologic outcomes among patients with SVI at RP. METHODS: We reviewed 19,519 patients who underwent RP and identified 2043 with SVI. Metastasis-free (MFS), cancer-specific (CSS), and overall survival (OS) were estimated for patients with SVI, stratified by the presence and number of pelvic lymph node metastases. Cox proportional hazards models were used to evaluate the independent association of the number of metastatic nodes and lymph node density with oncologic outcomes among patients with SVI, controlling for age, year of surgery, margin status, preoperative PSA, pathologic Gleason score, extraprostatic extension, and use of adjuvant therapies. RESULTS: At a median follow up of 12.1 years (IQR 7.0,18.6), 548 patients developed metastatic disease and 1331 died, including 406 who died from prostate cancer (PCa). We found that, among patients with SVI, the presence of a single positive lymph node was not associated with incrementally adverse oncologic outcomes compared to no nodal metastasis at RP, with 10-year MFS, CSS, and OS rates of 81.3% versus 78.3%(p = 0.18), 86.5% versus 89.8%(p = 0.32), and 72.8% versus 76.7%(p = 0.53), respectively. In contrast, on multivariable analyses, the presence of ≥2 metastatic nodes and a 20% lymph-node density cut off remained independently associated with worse survival. CONCLUSIONS: SVI represents an adverse pathologic feature such that the presence of a single positive pelvic lymph node did not further adversely impact prognosis. Meanwhile, a significant number of involved nodes was associated with decreased survival. These findings may aid in risk-stratification as well as clinical trial design for such high-risk patients following surgery.

Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) has phenotypic variability only partially explained by established biomarkers that do not readily assess pathologically important factors of inflammation and kidney fibrosis. We evaluated asymptomatic pyuria (AP), a surrogate marker of inflammation, as a biomarker for disease progression. Methods: We performed a retrospective cohort study of adult patients with ADPKD. Patients were divided into AP and no pyuria (NP) groups. We evaluated the effect of pyuria on kidney function and kidney volume. Longitudinal models evaluating kidney function and kidney volume rate of change with respect to incidences of AP were created. Results: There were 687 included patients (347 AP, 340 NP). The AP group had more women (65% versus 49%). Median ages at kidney failure were 86 and 80 years in the NP and AP groups (log rank, P=0.49), respectively, for patients in Mayo Imaging Class (MIC) 1A-1B as compared with 59 and 55 years for patients in MIC 1C-1D-1E (log rank, P=0.02), respectively. Compared with the NP group, the rate of kidney function (ml/min per 1.73 m2 per year) decline shifted significantly after detection of AP in the models, including all patients (-1.48; P<0.001), patients in MIC 1A-1B (-1.79; P<0.001), patients in MIC 1C-1D-1E (-1.18; P<0.001), and patients with PKD1 (-1.04; P<0.001). Models evaluating kidney volume rate of growth showed no change after incidence of AP as compared with the NP group. Conclusions: AP is associated with kidney failure and faster kidney function decline irrespective of the ADPKD gene, cystic burden, and cystic growth. These results support AP as an enriching prognostic biomarker for the rate of disease progression.

Kidney Cysts in Hypophosphatemic Rickets With Hypercalciuria: A Case Series.

Rationale & Objective: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare monogenic disorder caused by SLC34A3 pathogenic variants. HHRH is characterized by kidney phosphate wasting, hypophosphatemia, hypercalciuria, an elevated 1,25-dihydroxyvitamin D level, nephrocalcinosis, and urinary stone disease. Previously, we reported a 100% prevalence of kidney cysts in the related CYP24A1 deficiency. Thus, in the current study, we characterized cysts' presence in HHRH, another monogenic cause of hypercalciuria, nephrocalcinosis, and urinary stone disease. Study Design: Case series. Setting & Participants: Medical records from the Mayo Clinic and the Rare Kidney Stone Consortium monogenic stone disease database were queried for patients with a genetically confirmed HHRH diagnosis. The number, sizes, and locations of kidney cysts in each patient were recorded. Results: Twelve patients with SLC34A3 pathogenic variants were identified (7 monoallelic, 5 biallelic). Of these, 5 (42%) were males, and the median (Q1, Q3) ages were 16 years (13, 35 years) at clinical presentation and 42 years (20, 57 years) at genetic confirmation. Kidney cysts were present in 9 of 12 (75%) patients, and the median (Q1, Q3) age at first cyst detection was 41 years (13, 50 years). The median number of cysts per patient was 2.0 (0.5, 3.5). Fifty percent of adult patients had a cyst number that exceeded the 97.5th percentile of an age- and sex-matched control population. All children had at least 2 or more total cysts. None had a family history of cystic kidney disease. Limitations: Retrospective study, possible selection bias, single-center experience. Conclusions: A strong association between HHRH and kidney cysts was observed. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D and hypercalciuria may be potential cystogenic factors. Further studies are needed to understand how genetic changes in SLC34A3 favor cyst formation.

Congenital Heart Disease in Adults with Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is caused mainly by pathogenic variants in PKD1 or PKD2 encoding the polycystin-1 and -2 proteins. Polycystins have shown to have an essential role in cardiac development and function in animal models. In the current study, we describe the clinical association between ADPKD and congenital heart disease (CHD). METHODS: Medical records from Mayo Clinic were queried for all patients with confirmed ADPKD and CHD between 1993 and 2020. CHD was categorized into left-to-right shunt, obstructive, and complex lesions. Patent foramen ovale, mitral valve prolapse, and bicuspid aortic valve anomalies were excluded. RESULTS: Twenty-five out of 1,359 (1.84%) ADPKD patients were identified to have CHD. Of these, 84% were Caucasians and 44% were males. The median (Q1-Q3) age (years) at CHD diagnosis was 12.0 (2.0-43.5). Fourteen patients (56%) had left-to-right shunt lesions, 6 (24%) had obstructive lesions and 5 (20%) complex lesions. Seventeen patients (68%) had their defects surgically corrected at a median age (Q1-Q3) of 5.5 (2.0-24.7). Among 13 patients with available genetic testing, 12 (92.3%) had PKD1 pathogenic variants, and none had PKD2. The median (Q1-Q3) age at last follow-up visit was 47.0 (32.0-62.0) and median (Q1-Q3) eGFR was 35.8 (11.4-79.0) mL/min/1.73 m2. Three patients (12%) died; all of them had left-to-right shunt lesions. DISCUSSION/CONCLUSION: We observed a higher CHD frequency in ADPKD than the general population (1.84 vs. 0.4%). While only PKD1 pathogenic variants were identified in this cohort, further studies are needed to confirm this novel finding and understand the role of polycystins in the development of the heart and vessels.

Long-Term Risk of Clinical Progression Utilizing Magnetic Resonance Imaging Findings of Locally Recurrent Prostate Cancer in Patients with Biochemical Recurrence following Radical Prostatectomy.

PURPOSE: Our goal was to evaluate the long-term prognostic value of magnetic resonance imaging of the prostatectomy bed in patients with biochemical recurrence after radical prostatectomy for prostate cancer. MATERIALS AND METHODS: Men with biochemical recurrence after radical prostatectomy who were studied by prostatectomy bed magnetic resonance imaging for suspected local recurrence were retrospectively evaluated. Locally recurrent tumors were noted and measured from imaging reports. Patients with nodal/bone lesions at the time of imaging were excluded. Kaplan-Meier and Cox regression analyses were used to assess systemic progression-free and prostate cancer-specific survival. RESULTS: A total of 896 men were enrolled and the imaging positive and negative groups for local recurrent tumor consisted of 441 and 455 men, respectively. On univariate analysis, preoperative prostate specific antigen (p=0.02), clinical tumor stage (p=0.006), pathological Gleason score from prostatectomy (p=0.02), subsequent salvage radiotherapy (p <0.001), biochemical recurrence to magnetic resonance imaging time interval (p <0.001), age at magnetic resonance imaging (p=0.047) and prostate specific antigen at magnetic resonance imaging (p <0.001) were significantly different between magnetic resonance imaging positive and negative groups. Patients with negative magnetic resonance imaging results had worse systemic progression-free survival rates (p=0.025) and better prostate cancer-specific survival (p=0.016) than those with recurrence. Larger lesion size significantly increased risk of prostate cancer death (hazard ratio: 1.07; p <0.001). On multivariable analysis, pathological Gleason scores ≥7 were independent prognostic factors of systemic progression (p <0.05). CONCLUSIONS: Prostatectomy bed magnetic resonance imaging provides long-term prognostic information for the evaluation of patients with biochemical recurrence after prostatectomy. Post-prostatectomy patients with recurrent lesions on imaging had longer progression-free survival but shorter prostate cancer-specific survival compared to those without lesions. Additionally, those with larger lesions were associated with poorer cancer-specific survival.

Long-term device survival and quality of life outcomes following artificial urinary sphincter placement.

BACKGROUND: Artificial urinary sphincter (AUS) placement is the standard for treatment of severe male stress urinary incontinence (SUI). While there is evidence to suggest satisfactory device survival, there is a paucity of data addressing long-term quality of life outcomes. METHODS: We identified patients who underwent primary AUS placement from 1983 to 2016. We assessed rates of secondary surgery (overall, device infection/erosion, urethral atrophy, malfunction) and factors associated with these endpoints. Quality of life was evaluated by pad usage and Patient Global Impression of Improvement (PGI-I) at various time points from primary surgery. Follow-up was obtained in clinic or by phoned/mailed correspondence. RESULTS: During the study time frame, 1,154 patients were eligible and included in the analysis. Patients had a median age of 70 years (IQR, 65-75 years) and median follow up of 5.4 years (IQR, 1.6-10.5 years). Overall device survival was 72% at 5 years, 56% at 10 years, 41% at 15 years, and 33% at 20 years. On univariate analysis, variables associated with need for secondary surgery were prior cryotherapy (HR 2.7; 95% CI, 1.6-4.6; P<0.01) or radiation therapy (HR 1.4; 95% CI, 1.1-1.7; P=0.01). On multivariable analysis, only cryotherapy remained significantly associated with this endpoint (HR 2.4; 95% CI, 1.3-4.2; P<0.01). While 36% and 23% of patients 5-10 years out from surgery and >10 years out from surgery, respectively, reported using a security pad or less per day, 78% and 81% of those patients, respectively, reported their PGI-I as at least "much better". CONCLUSIONS: AUS placement has excellent long-term outcomes, and is associated with sustained improvement in patient quality of life.

The impact of prior external beam radiation therapy on device outcomes following artificial urinary sphincter revision surgery.

BACKGROUND: Previous reports on the effect of radiation therapy on primary artificial urinary sphincter (AUS) device survival have met with conflicting results, and data evaluating this after revision surgery is sparse. Thus, we evaluated AUS device outcomes after revision surgery, and compared them among individuals who did versus did not undergo prior radiation therapy. METHODS: A database of patients who underwent AUS revision surgery at our institution was used to perform a retrospective review. Device survival endpoints, including overall survival, infection/erosion, urethral atrophy, and device malfunction were evaluated. Overall device survival (i.e., any repeat surgery) was compared between groups, stratified by external beam radiation status, via Kaplan-Meier method. Proportional hazard regression and competing risk analysis were used to evaluate association between prior radiation therapy and device outcomes. RESULTS: From 1983 to 2016, a total of 527 patients underwent AUS revision surgery. Of these, 173 (33%) patients had undergone prior radiation therapy. Patients with prior radiation therapy were more likely to have diabetes mellitus (22% vs. 14%; P=0.05), hypertension (71% vs. 56%; P<0.01), previous vesicourethral anastomotic stenosis (41% vs. 19%; P<0.0001), as well as prior androgen deprivation therapy (26% vs. 6%; P<0.0001). Overall, there was not enough evidence to support the existence of a significant difference in device survival among patients with or without a history of radiotherapy, with 1- and 5-year-overall survival of 84% vs. 85% and 51% vs. 64%, respectively (P=0.07). On competing risk analysis, a history of pelvic radiation therapy was not enough evidence to support a significant association with the risk of device infection/erosion, mechanical failure, or urethral atrophy. CONCLUSIONS: There was not enough evidence of a difference in the rate of device erosion or infection, cuff atrophy, malfunction, or overall device survival following AUS revision surgery between patients with and without a history of pelvic radiation. These findings may be helpful when counseling patients regarding outcomes after AUS revision.

Impact of metabolic syndrome on functional outcomes and complications of surgical treatment of prostate cancer.

BACKGROUND: Metabolic syndrome (MetS) has a negative impact on functional recovery and complications after many surgical procedures. AIM: To assess the role of Mets on functional outcomes and complications after radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS: Complete data were collected from 5758 patients, undergoing RP at a single referral centers in a 10-year period and the presence of MetS before surgery was ascertained in 17.7% of them using a modified version of the IDF-AHA/NHLBI criteria. Outcomes included 1-year continence and potency rates, early (≤90 days) and late (>90 days) complications. RESULTS: Postoperative continence (no pads) was significantly less likely in MetS patients (75.4% vs 82.6%, P < .01), despite no difference in preoperative continence. Erections with or without therapy were reached in 55.8% of non-MetS and 41.8% of MetS patients (P < .01), in this case a significant difference in preoperative function was seen. No differences in early and late complications, except for wound infections (5.8% vs 3.9%, P < .01) were observed. CONCLUSIONS: In the present study RP was safe from the complications standpoint in MetS patients, but the presence of the syndrome was a significant risk factor for post-RP incontinence and impotence.

Large Chromosomal Rearrangements Yield Biomarkers to Distinguish Low-Risk From Intermediate- and High-Risk Prostate Cancer.

OBJECTIVE: To test the hypothesis that chromosomal rearrangements (CRs) can distinguish low risk of progression (LRP) from intermediate and high risk of progression (IHRP) to prostate cancer (PCa) and if these CRs have the potential to identify men with LRP on needle biopsy that harbor IHRP PCa in the prostate gland. PATIENTS AND METHODS: Mate pair sequencing of amplified DNA from pure populations of Gleason patterns in 154 frozen specimens from 126 patients obtained between August 14, 2001, and July 15, 2011, was used to detect CRs including abnormal junctions and copy number variations. Potential CR biomarkers with higher incidence in IHRP than in LRP to cancer and having significance in PCa biology were identified. Independent validation was performed by fluorescence in situ hybridization in 152 specimens from 124 patients obtained between February 12, 2002, and July 12, 2008. RESULTS: The number of abnormal junctions did not distinguish LRP from IHRP. Loci corresponding to genes implicated in PCa were more frequently altered in IHRP. Integrated analysis of copy number variations and microarray data yielded 6 potential markers that were more frequently detected in Gleason pattern 3 of a Gleason score 7 of PCa than in Gleason pattern 3 of a Gleason score 6 PCa. Five of those were cross-validated in an independent sample set with statistically significant areas under the receiver operating characteristic curves (AUCs) (P≤.01). Probes detecting deletions in PTEN and CHD1 had AUCs of 0.87 (95% CI, 0.77-0.97) and 0.73 (95% CI, 0.60-0.86), respectively, and probes detecting gains in ASAP1, MYC, and HDAC9 had AUCs of 0.71 (95% CI, 0.59-0.84), 0.82 (95% CI, 0.71-0.93), and 0.77 (95% CI, 0.66-0.89), respectively (for expansion of gene symbols, use search tool at www.genenames.org). CONCLUSION: Copy number variations in regions encompassing important PCa genes were predictive of cancer significance and have the potential to identify men with LRP PCa by needle biopsy who have IHRP PCa in their prostate gland.

Role of Metabolic Syndrome on Perioperative and Oncological Outcomes at Radical Prostatectomy in a Low-risk Prostate Cancer Cohort Potentially Eligible for Active Surveillance.

BACKGROUND: Metabolic syndrome (MetS) is considered a potential risk factor for adverse outcomes after radical prostatectomy (RP). Furthermore, studies about the effect of MetS on low-risk prostate cancer (PCa) and its implications in active surveillance (AS) are limited. OBJECTIVE: To investigate the role of MetS (using International Diabetes Federation-American Heart Association/National Heart, Lung, and Blood Institute criteria) on perioperative and oncological outcomes after RP in low-risk PCa and in a subgroup potentially eligible for AS. DESIGN, SETTING, AND PARTICIPANTS: A total of 3662 patients treated with RP for low-risk PCa and further stratified as very low risk (VLR) PCa-prostate-specific antigen density of ≤0.15ng/ml/cm3, ≤2 cores involved, and no core with >50% cancer involvement-at a tertiary referral hospital were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes analyzed were pathological outcomes, perioperative complications, biochemical failure (BCF), and overall survival. Pathological outcomes and complications were analyzed with logistic regression models. Kaplan-Meier curves and Cox proportional hazards models were used to analyze survival outcomes. RESULTS AND LIMITATIONS: In univariate/multivariate analyses, MetS was associated with upgrading and positive surgical margins in the entire cohort, upgrading only in the VLR group. In Kaplan-Meier analysis, MetS patients had a higher rate of overall death (p<0.0001) and BCF (p=0.03) for MetS patients. In the VLR group, no differences were found for BCF (p=0.064). Further, in Cox proportional hazards models, MetS was not associated with BCF (hazard ratio=1.23; 95% confidence interval [CI]=0.95-1.60, p=0.12). MetS patients had a higher rate of complications compared with non-MetS patients (23.7% vs 19.7%; p=0.01). In multivariate analysis, MetS was associated with a higher rate of complications (odds ratio=1.24, 95% CI=1.04-1.49, p=0.018) but did not impact the rate of major ones. This study is limited by its retrospective design. CONCLUSIONS: In low-risk PCa treated with RP but potentially eligible for AS, MetS impacted perioperative and pathological outcomes, suggesting further study of MetS in patients undergoing AS. PATIENT SUMMARY: Metabolic syndrome negatively impacts perioperative and pathological outcomes in low-risk prostate cancer patients treated with radical prostatectomy but potentially eligible for active surveillance, in a large American single-center cohort. These findings suggest the need for a more cautious approach to low-risk prostate cancer in patients with metabolic syndrome.

Risk factors for subsequent urethral atrophy in patients undergoing artificial urinary sphincter placement.

OBJECTIVE: Artificial urinary sphincter (AUS) device failure or revision can be due to multiple etiologies including erosion, infection, mechanical malfunction, and urethral atrophy. However, few studies have evaluated factors that predispose patients to urethral atrophy. Here, we sought to identify preoperative and perioperative risk factors associated with urethral atrophy in men undergoing primary artificial urinary sphincter (AUS) placement for stress urinary incontinence. MATERIAL AND METHODS: From 1987 to 2013, 1829 AUS procedures were performed at our institution. A total of 1068 patients underwent primary AUS placement and were the focus of our study. Multiple clinical and surgical variables were evaluated for a potential association with revision for atrophy. Those found to be associated with atrophy and relevant competing risks were further evaluated on multivariable analysis. RESULTS: With a median follow-up of 4.2 years (IQR 1.3-8.1), 89 men (8.3%) had urethral atrophy requiring reoperation. Median time to revision was 4.5 years (IQR 1.9-7.6). On univariable analysis, only smaller cuff size (4.0-cm versus 4.5-cm; HR 3.1, p=0.04) was associated with an increased rate of urethral atrophy. Notably, patient age at the time of surgery (p=0.62), body mass index (0.22), and smoking status (p=1.00) were not associated with a risk of atrophy. On multivariable analysis smaller urethral cuff size remained significant (HR 2.8, 95% CI 1.1-7.1; p=0.01). CONCLUSION: Revision surgery for urethral atrophy was performed in approximately 8% of men undergoing primary AUS placement. Utilization of a smaller AUS cuff size appears to be an independent factor associated with increased rate of urethral atrophy.

Impact of metabolic syndrome on oncologic outcomes at radical prostatectomy.

PURPOSE: The associations between metabolic syndrome (MetS) and prostate cancer (CaP) outcomes following radical prostatectomy (RP) are not clear. This study aims to understand the role of MetS in influencing oncological outcomes at RP. MATERIALS AND METHODS: Patients who underwent RP for CaP at our institution from 2000 to 2010 were identified; MetS prior to RP was ascertained with a modified version of the IDF-AHA/NHLBI using ICD-9 codes. Histopathological outcomes included surgical margins, pathological stage, and Gleason score (GS) upgrading. Long-term outcomes included biochemical recurrence (BCR), local recurrence, systemic progression, and CaP-specific mortality. Multivariable adjusted logistic regression and Cox proportional hazards regression assessed the association between MetS status and histopathological and long-term outcomes, respectively. RESULTS: Of 8,504 RP patients, 1,054 (12.4%) had MetS at the time of RP. MetS patients were older, had higher biopsy GS, but lower pre-op prostatic specific antigen (PSA), higher pathological GS, and larger prostate volume. Adjusted logistic regression suggested an association between MetS and positive margins (odds ratio [OR] = 1.22, P = 0.025) and GS upgrading (OR = 1.28, P = 0.002). There was evidence of an increased risk of local recurrence (hazard ratio [HR] = 1.33, P = 0.037) and CaP-specific mortality (HR = 1.58, P < 0.001) for MetS patients. There was no evidence to suggest an association with BCR or systemic progression. CONCLUSION: Men with MetS are at higher risk of GS upgrade and positive surgical margins at surgery, local recurrence, and CaP-specific mortality. Pathological stage, BCR, and systemic progression were not associated with MetS. Our data may be useful in patients' counseling, especially when active surveillance is an option.

Outcomes and Prognostic Factors in Men Receiving Androgen Deprivation Therapy for Prostate Cancer Recurrence after Radical Prostatectomy.

PURPOSE: We sought to determine clinicopathological factors associated with early progression in men on androgen deprivation therapy as well as cancer specific and overall survival. We also assessed whether certain prostate specific antigen thresholds at androgen deprivation therapy initiation are associated with poorer outcomes. MATERIALS AND METHODS: We identified 2,418 men with rising prostate specific antigen after undergoing radical prostatectomy at a single institution between 1987 and 2007 in a prospectively maintained registry. Early progression was defined as clinical progression within 2 years of initiating androgen deprivation therapy. The primary study outcome was cancer specific and overall survival. RESULTS: The risk of early progression while on androgen deprivation therapy was lower for prostate specific antigen doubling time 3 to less than 9 months (OR 0.19) and less than 9 months or longer (OR 0.10, each p <0.001) prior to androgen deprivation therapy. Independent predictors of cancer specific survival were metastatic disease at androgen deprivation therapy initiation (HR 2.60), prostate specific antigen 5 to 50 ng/ml (HR 2.68) and 50 ng/ml or greater (HR 4.33), and doubling time 3 to less than 9 months (HR 0.54) and 9 months or longer (HR 0.45, all p <0.001). Independent predictors of overall survival were prostate specific antigen 5 to 50 ng/ml (HR 3.10) and 50 ng/ml or greater (HR 5.20, each p <0.001). CONCLUSIONS: In men in whom androgen deprivation therapy was initiated for relapse after radical prostatectomy prostate specific antigen doubling time less than 3 months and prostate specific antigen 5 ng/ml or greater were adverse prognostic factors for early progression and cancer specific survival. Prostate specific antigen 5 ng/ml or greater also predicted shorter overall survival. Longer doubling time and prostate specific antigen less than 5 ng/ml were associated with lower risk and these men may not require immediate androgen deprivation therapy.

Examining the association between adiposity and biochemical recurrence after radical prostatectomy.

INTRODUCTION: Herein, we examined the association between adiposity, as measured by computed tomography (CT), and biochemical recurrence (BCR) after radical prostatectomy (RP). METHODS: Using axial CT images, preoperative fat mass index (FMI) was calculated for 698 men who underwent RP from 2007-2010 by using measurements of total surface area of adipose tissue at the L3 level. Obesity was classified according to National Health and Nutrition Examination Survey (NHANES) standards for obesity (FMI >9 kg/m2). The associations between obesity and the distribution of adiposity (visceral vs. subcutaneous) with BCR were examined using the Kaplan-Meier method and Cox proportional hazards regression analyses. RESULTS: Obese men were older than non-obese men (63.0 vs. 60.7 years; p<0.001), but were similar with regards to all other clinical and pathological characteristics. With a median followup of six years, 152 patients were diagnosed with BCR. Five-year BCR-free survival was similar between obese and non-obese patients (80.6% vs. 82.1%; p=0.27). Furthermore, in multivariable analyses, obesity was not independently associated with the risk of BCR (hazard ratio [HR] 1.02; 95% confidence interval [CI] 0.73-1.43). Similar results were obtained when analyzing FMI as a continuous variable (HR 1.02; 95% CI 0.94-1.09 for each 1 kg/m2 increase in FMI). Additionally, neither visceral adiposity, subcutaneous adiposity, or visceral-to-subcutaneous adiposity ratio were associated with BCR (all p>0.05) in multivariable analyses. CONCLUSIONS: Neither total abdominal adiposity nor the distribution of adiposity were independently associated with BCR after RP in this study. As such, the presence of obesity may not be a marker of increased oncological risk after RP.

The Association Between Sarcopenia and Oncologic Outcomes After Radical Prostatectomy.

PURPOSE: Sarcopenia is associated with inferior perioperative and oncologic outcomes in patients undergoing surgery for multiple malignancies. The purpose of this study was to evaluate the association between sarcopenia and outcomes after radical prostatectomy (RP) for men with prostate cancer. PATIENTS AND METHODS: Using a representative computed tomographic image from the L3 level, preoperative skeletal muscle indices (SMI) calculated for 698 patients who underwent RP between 2007 and 2010. Patients were classified as sarcopenic if they had a SMI < 55 cm2/kg2 according to international consensus. The associations between sarcopenia and biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM) were investigated by Cox proportional hazards regression. RESULTS: Sarcopenic patients were older than nonsarcopenic patients (mean age, 63.0 vs. 60.4 years, P < .001) but were otherwise similar with regard to clinical and pathologic characteristics. There was no significant difference in the perioperative complication rate after RP between sarcopenic and nonsarcopenic patients (16.5% vs. 17.4%, P = .82). At a median follow-up after surgery of 6.0 years, 152 patients were diagnosed with BCR, patients were diagnosed with SP, and 50 patients died. In multivariable analysis, the presence of sarcopenia was not significantly associated with the risks of BCR, SP, or ACM. Similar results were obtained when analyzing SMI as a continuous variable. CONCLUSION: Sarcopenia was not found to be independently associated with perioperative complications or oncologic outcomes after RP. As such, the presence of sarcopenia may not be prognostic marker for inferior outcomes among men with localized prostate cancer undergoing RP.

Heterogeneity of risk within Gleason 4 + 4, 4 + 5 and 5 + 4 prostate cancer.

OBJECTS: This study hypothesized that biopsy Gleason score 8 (b.G.S. 8) disease may dilute the substantial poor risk associated with b.G.S. 9 disease, specifically associated with primary Gleason 5 disease. MATERIALS AND METHODS: The study reviewed 18,299 patients treated with radical prostatectomy (R.P.) between 1990 and 2011, and identified 1,080 men with b.G.S. 4 + 4 (n = 614, 56.9%), 4 + 5 (n = 347, 32.1%), and 5 + 4 (n = 119, 11%) P.Ca. Variation trends of high risk prostate cancer (H.R.P.Ca.) characteristics were recorded over time: The association of b.G.S. with survival outcomes was assessed using Kaplan Meier and multivariable Cox regression analyses. Median follow-up was 6.1 years (I.Q.R. = 3-10.8). RESULTS: The number of patients included in H.R.P.Ca. due to their b.G.S. increased consistently over time. On multivariable regression, b.G.S. 4 + 5 and b.G.S. 5 + 4 vs b.G.S. 4 + 4 were found to be independently associated with seminal vesical involvement (Odds ratio [O.R.] = 1.58 and 2.22; p < 0.005), extracapsular extension (O.R. = 1.51 and 1.7; p < 0.02) and surgical margins (O.R. = 1.50 and 2.03; p < 0.01), respectively. Ten-year cancer-specific survival was 83%, 73% and 70% in patients with b.G.S. 4 + 4, 4 + 5 and 5 + 4, respectively (p < 0.01). b.G.S. 4 + 5 and b.G.S. 5 + 4 compared to b.G.S. 4 + 4 were associated with an increased risk of cancer-specific mortality (C.S.M.) (Hazard ratio = 1.76, p = 0.02 and 2.38, p = 0.003, respectively). CONCLUSIONS: B.G.S. 9 and specifically pattern 5 + 4 P.Ca. is associated with substantial disease burden, adverse pathological features and the presence of locally advanced disease, in addition to inferior survival outcomes in comparison to b.G.S. 4 + 4 disease. Distinction of b.G.S. 9 patients from b.G.S. 8 patients at diagnosis may permit more precise pre-treatment risk stratification.

Comparison of Pathological and Oncologic Outcomes of Favorable Risk Gleason Score 3 + 4 and Low Risk Gleason Score 6 Prostate Cancer: Considerations for Active Surveillance.

PURPOSE: Recent NCCN® (National Comprehensive Cancer Network®) Guidelines® show that patients with biopsy Gleason score 3 + 4/Grade Group 2 but otherwise favorable features are active surveillance candidates. However, little is known about the long-term outcomes compared to that in men in the low risk Gleason score 6/Grade Group 1 group. We sought to clarify the risk of adverse features and oncologic outcomes in surgically treated, favorable Grade Group 2 vs 1 cases. MATERIALS AND METHODS: We queried our prospectively maintained radical prostatectomy database for all 8,095 patients with biopsy Grade Group 1 or 2 prostate cancer who otherwise fulfilled the NCCN low risk definition of prostate specific antigen less than 10 ng/ml and cT2a or less, and who underwent radical prostatectomy from 1987 to 2014. Multivariable logistic regression and Kaplan-Meier methods were used to compare pathological and oncologic outcomes. RESULTS: Organ confined disease was present in 93.9% and 82.6% of Grade Group 1 and favorable intermediate risk Grade Group 2 cases while seminal vesicle invasion was noted in 1.7% and 4.7%, and nodal disease was noted in 0.3% and 1.8%, respectively (all p <0.0001). On multivariable logistic regression biopsy proven Grade Group 2 disease was associated with a threefold greater risk of nonorgan confined disease (OR 3.1, 95% CI 1.7-5.7, p <0.001). The incidence of late treatment (more than 90 days from surgery) in Grade Group 1 vs 2 was 3.1% vs 8.5% for hormonal therapy and 6.0% vs 12.2% for radiation (p <0.001). In the Grade Group 1 vs 2 cohorts the 10-year biochemical recurrence-free survival rate was 88.9% vs 81.2% and the 10-year systemic progression-free survival rate was 99% vs 96.5% (each p <0.001). CONCLUSIONS: Men at favorable risk with Grade Group 2 disease who are considering active surveillance should be informed of the risks of harboring adverse pathological features which impact secondary therapies and an increased risk of cancer progression.

Can time to failure predict the faulty component in artificial urinary sphincter device malfunctions?

OBJECTIVE: Artificial urinary sphincter malfunctions can occur in any of the individual components. Preoperative identification of the malfunctioning component can be valuable for patient counseling and surgical planning. The optimal strategy for repair of failed artificial urinary sphincter components is debated given the relative rarity of the situation. The aim of the present study was to evaluate the relationship of time to failure with failed artificial urinary sphincter component and to compare our outcomes of specific component versus complete device replacement. METHODS: From 1983 to 2011, 1805 artificial urinary sphincter procedures were carried out at Mayo Clinic (Rochester, Minnesota, USA), of which 1072 patients underwent primary artificial urinary sphincter placement. Clinical variables, including time to failure, were evaluated for association with component failure. Bootstrap analysis was used to estimate the differences in time to reach a fixed percentage of component failure. RESULTS: A total of 115 patients experienced device failure at a median follow up of 4.2 years. Urethral cuff, abdominal reservoir, scrotal pump and tubing malfunction occurred in 53 (4.9%), 26 (2.4%), 11 (1%) and 25 (2.3%) patients, respectively. Increasing age at the time of primary surgery was protective of cuff malfunction (hazard ratio 0.97, P = 0.04). Time to 3% urethral cuff failure outpaced other component failures (P < 0.05). Secondary failure-free rates after whole device versus specific component revisions were comparable (P = 0.38). CONCLUSIONS: Clinical predictors for artificial urinary sphincter failure continue to be difficult to establish. Although single component versus entire device replacement have similar outcomes, if pursuing single component revision, we recommend cuff-first interrogation in devices in place for >3 years, as this represents the most likely component to fail.