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.

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.

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.

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.

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.

Independent Validation of the American Joint Committee on Cancer 8th Edition Prostate Cancer Staging Classification.

PURPOSE: We sought to independently validate the AJCC (American Joint Committee on Cancer) 8th edition prostate cancer staging classification, which includes the elimination of pT2 subcategories and the reclassification of patients with prostate specific antigen 20 ng/ml or greater and Gleason Grade Group 5 as stage groups III-A and III-C, respectively. MATERIALS AND METHODS: We identified 13,839 men who underwent radical prostatectomy at Mayo Clinic between 1987 and 2011 from our institutional registry. Outcomes included biochemical recurrence-free, metastasis-free and cancer specific survival. Kaplan-Meier analyses and Cox regression models with the c-index were used. RESULTS: Median followup was 10.5 years (IQR 7.1-15.3). Among patients with pT2 prostate cancer the subclassification demonstrated limited discrimination for biochemical recurrence-free, metastasis-free and cancer specific survival (c-index 0.531, 0.545 and 0.525, respectively). At the same time patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly worse 15-year biochemical recurrence-free survival (42.2% vs 58.8%), metastasis-free survival (78.2% vs 88.8%) and cancer specific survival (88.0% vs 94.4%, all p <0.001) than patients with 7th edition stage group II prostate cancer and prostate specific antigen less than 20 ng/ml. However, patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly better 15-year biochemical recurrence-free survival (42.2% vs 31.3%, p = 0.007), metastasis-free survival (78.2% vs 68.0%, p <0.001) and cancer specific survival (88.0% vs 83.4%, p = 0.01) than patients with 7th edition stage group III. Also, patients with 7th edition stage group II prostate cancer and Gleason Grade Group 5 had significantly worse 15-year biochemical recurrence-free survival (37.1% vs 57.9%, p <0.001), metastasis-free survival (63.8% vs 88.5%, p <0.001) and cancer specific survival (73.0% vs 94.3%, p <0.001) than patients with 7th edition stage group II prostate cancer and Gleason Grade Group 1-4 as well as worse 15-year cancer specific survival (73.0% vs 83.4%, p = 0.005) than patients with 7th edition stage group III prostate cancer. CONCLUSIONS: Our data support the changes in the new AJCC classification.

Impact of Radical Prostatectomy on Long-Term Oncologic Outcomes in a Matched Cohort of Men with Pathological Node Positive Prostate Cancer Managed by Castration.

PURPOSE: Long-term data supporting the role of primary tumor resection in node positive prostate cancer are lacking. We evaluated the impact of adding radical retropubic prostatectomy to surgical castration on long-term oncologic outcomes in pathological node positive prostate cancer. MATERIALS AND METHODS: We identified men who underwent pelvic lymphadenectomy and orchiectomy within 90 days for pathological node positive prostate cancer from 1966 to 1995. Men treated with radical retropubic prostatectomy in addition to orchiectomy were matched 1:1 to men who underwent orchiectomy alone based on age, year of surgery, clinical grade, clinical T stage, number of positive nodes and preoperative serum prostate specific antigen, the latter from 1987 and thereafter. Kaplan-Meier and Cox regression analyses were done to compare cancer specific and overall survival. RESULTS: The matched cohort included 158 men with 79 in each group. Of men who underwent orchiectomy alone 76 died, including 60 of prostate cancer. Of patients treated with radical retropubic prostatectomy plus orchiectomy 70 died, including 28 of prostate cancer. On Kaplan-Meier analyses prostatectomy plus orchiectomy vs orchiectomy alone was associated with prolonged cancer specific survival (at 20 years 59% vs 18%, log rank p <0.001) and overall survival (at 20 years 22% vs 9%, log rank p <0.001). In Cox models prostatectomy plus orchiectomy vs orchiectomy alone was associated with improved cancer specific survival (HR 0.28, 95% CI 0.17-0.46, p <0.001) and overall survival (HR 0.48, 95% CI 0.34-0.66, p <0.001). Findings were similar in the subset with available preoperative prostate specific antigen values. CONCLUSIONS: With lifelong followup in nearly the entire cohort, this study demonstrates that adding radical retropubic prostatectomy to surgical castration for pathological node positive prostate cancer is associated with improved cancer specific and overall survival. When technically feasible in well selected patients, aggressive locoregional resection should be considered for node positive prostate cancer as part of a multimodal approach.

HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study.

BACKGROUND: HSD3B1 (1245A>C) has been mechanistically linked to castration-resistant prostate cancer because it encodes an altered enzyme that augments dihydrotestosterone synthesis from non-gonadal precursors. We postulated that men inheriting the HSD3B1 (1245C) allele would exhibit resistance to androgen-deprivation therapy (ADT). METHODS: In this multicohort study, we determined HSD3B1 genotype retrospectively in men treated with ADT for post-prostatectomy biochemical failure and correlated genotype with long-term clinical outcomes. We used data and samples from prospectively maintained prostate cancer registries at the Cleveland Clinic (Cleveland, OH, USA; primary study cohort) and the Mayo Clinic (Rochester, MN, USA; post-prostatectomy and metastatic validation cohorts). In the post-prostatectomy cohorts, patients of any age were eligible if they underwent prostatectomy between Jan 1, 1996, and Dec 31, 2009 (at the Cleveland Clinic; primary cohort), or between Jan 1, 1987, and Dec 31, 2011 (at the Mayo Clinic; post-prostatectomy cohort) and were treated with ADT for biochemical failure or for non-metastatic clinical failure. In the metastatic validation cohort, patients of any age were eligible if they were enrolled at Mayo Clinic between Sept 1, 2009, and July 31, 2013, with metastatic castration-resistant prostate cancer. The primary endpoint was progression-free survival according to HSD3B1 genotype. We did prespecified multivariable analyses to assess the independent predictive value of HSD3B1 genotype on outcomes. FINDINGS: We included and genotyped 443 patients: 118 in the primary cohort (who underwent prostatectomy), 137 in the post-prostatectomy validation cohort, and 188 in the metastatic validation cohort. In the primary study cohort, median progression-free survival diminished as a function of the number of variant alleles inherited: 6·6 years (95% CI 3·8-not reached) in men with homozygous wild-type genotype, 4·1 years (3·0-5·5) in men with heterozygous variant genotype, and 2·5 years (0·7 to not reached) in men with homozygous variant genotype (p=0·011). Relative to the homozygous wild-type genotype, inheritance of two copies of the variant allele was predictive of decreased progression-free survival (hazard ratio [HR] 2·4 [95% CI 1·1-5·3], p=0·029), as was inheritance of one copy of the variant allele (HR 1·7 [1·0-2·9], p=0·041). Findings were similar for distant metastasis-free survival and overall survival. The effect of the HSD3B1 genotype was independently confirmed in the validation cohorts. INTERPRETATION: Inheritance of the HSD3B1 (1245C) allele that enhances dihydrotestosterone synthesis is associated with prostate cancer resistance to ADT. HSD3B1 could therefore potentially be a powerful genetic biomarker capable of distinguishing men who are a priori likely to fare favourably with ADT from those who harbour disease liable to behave more aggressively, and who therefore might warrant early escalated therapy. FUNDING: Prostate Cancer Foundation, National Institutes of Health, US Department of Defense, Howard Hughes Medical Institute, American Cancer Society, Conquer Cancer Foundation of the American Society of Clinical Oncology, Cleveland Clinic Research Programs Committee and Department of Radiation Oncology, Gail and Joseph Gassner Development Funds.

Integrated analysis of the genomic instability of PTEN in clinically insignificant and significant prostate cancer.

Patients with clinically insignificant prostate cancer remain a major over-treated population. PTEN loss is one of the most recurrent alterations in prostate cancer associated with an aggressive phenotype, however, the occurrence of PTEN loss in insignificant prostate cancer has not been reported and its role in the separation of insignificant from significant prostate cancer is unclear. An integrated analysis of PTEN loss was, therefore, performed for structural variations, point mutations and protein expression in clinically insignificant (48 cases) and significant (76 cases) prostate cancers treated by radical prostatectomy. Whole-genome mate pair sequencing was performed on tumor cells isolated by laser capture microdissection to characterize PTEN structural alterations. Fluorescence in situ hybridization probes were constructed from the sequencing data to detect the spectrum of these PTEN alterations. PTEN loss by mate pair sequencing and fluorescence in situ hybridization occurred in 2% of insignificant, 13% of large volume Gleason score 6, and 46% of Gleason score 7 and higher cancers. In Gleason score 7 cancers with PTEN loss, PTEN alterations were detected in both Gleason pattern 3 and 4 in 57% of cases by mate pair sequencing, 75% by in situ hybridization and 86% by immunohistochemistry. PTEN loss by sequencing was strongly associated with TMPRSS2-ERG fusion, biochemical recurrence, PTEN loss by in situ hybridization and protein loss by immunohistochemistry. The complex nature of PTEN rearrangements was unveiled by sequencing, detailing the heterogeneous events leading to homozygous loss of PTEN. PTEN point mutation was present in 5% of clinically significant tumors and not in insignificant cancer or high-grade prostatic intraepithelial neoplasia. PTEN loss is infrequent in clinically insignificant prostate cancer, and is associated with higher grade tumors. Detection of PTEN loss in Gleason score 6 cancer in a needle biopsy specimen indicates a higher likelihood of clinically significant prostate cancer.

Long-Term Quality of Life and Functional Outcomes among Primary and Secondary Artificial Urinary Sphincter Implantations in Men with Stress Urinary Incontinence.

PURPOSE: There remains a paucity of data regarding subjective and functional outcomes after artificial urinary sphincter implantation. Therefore, we evaluated long-term differences in quality of life after primary and secondary artificial urinary sphincter surgery. MATERIALS AND METHODS: Men were invited to participate in a mail-in survey assessing artificial urinary sphincter status, patient satisfaction and urinary control. Patients with primary (467) and secondary (122) artificial urinary sphincter devices without an event were included in the study. Differences between the cohorts including quality of life (10-point scale, maximum 100) and functional outcomes were evaluated. RESULTS: Overall 229 (49%) patients with primary and 49 (40%) with secondary artificial urinary sphincters completed the survey at a median of 8.3 years. Patients with primary and secondary artificial urinary sphincter devices reported similar artificial urinary sphincter quality of life (score 74 vs 74). There were no significant differences in urinary continence outcomes including use of 1 pad or less daily (56% vs 55%), frequency of leakage 1 time or more per day (81% vs 71%) or degree of minimal leakage related bother (64% vs 55%). At less than 5 vs 10 or more years there was a significant reduction in artificial urinary sphincter quality of life (86 vs 73, p=0.007). Urinary continence also declined with time, including perceived urinary control (85% vs 53%, p=0.004), minimal leakage related bother (76% vs 59%, p=0.05) and use of 1 pad or less daily (67% vs 55%, p=0.07). On univariate analysis no clinical variables, including secondary revision, were associated with satisfaction or continence outcomes. CONCLUSIONS: We noted a high level of artificial urinary sphincter quality of life, acceptable urinary control and no difference in functional outcomes between men undergoing primary or secondary artificial urinary sphincter surgery. However, the time related decline in satisfaction and continence highlights the need for patient counseling regarding long-term artificial urinary sphincter functional outcomes.

The Impact of Prior Radiation Therapy on Artificial Urinary Sphincter Device Survival.

PURPOSE: The literature on artificial urinary sphincter device survival in individuals with a history of radiation therapy is conflicting. We assess device survival outcomes among individuals after prior radiation therapy exposure undergoing primary artificial urinary sphincter placement. MATERIALS AND METHODS: An institutional review board approved database of all patients who underwent artificial urinary sphincter surgery from 1999 to 2011 was used to assess device survival in patients treated with radiotherapy compared to individuals without radiotherapy exposure. Hazard regression and competing risk analysis were used to determine the association between radiation therapy and device outcomes. RESULTS: From 1999 to 2011 a total of 872 patients underwent artificial urinary sphincter surgery at our institution. Of these patients 489 underwent primary artificial urinary sphincter placement, with 181 of 489 (37%) having received radiation therapy. Patients with prior radiation therapy were older (median age 72.0 vs 70.1 years, p <0.01) and had a higher median body mass index (29.4 vs 28.6 kg/m(2), p <0.03) than those without radiation exposure. Rates of diabetes mellitus and hypertension were similar between the 2 groups. There was no significant difference in overall device survival between individuals who received radiation therapy and those without radiation therapy exposure, with 1 and 5-year device survival rates of 92% vs 90% and 77% vs 74%, respectively (p=0.24). CONCLUSIONS: While individuals who underwent radiation therapy were significantly older and had a higher body mass index, device survival was not significantly different between the 2 groups when using a cuff size greater than 3.5 cm. These findings will assist the urologist with the preoperative counseling of men undergoing primary artificial urinary sphincter placement with a history of radiation therapy.

Artificial Urinary Sphincter Mechanical Failures-Is it Better to Replace the Entire Device or Just the Malfunctioning Component?

PURPOSE: We evaluate the characteristics of artificial urinary sphincter mechanical failures and compare outcomes based on the surgical revision strategy, replacing only the failed component or the entire device. MATERIALS AND METHODS: A total of 1,802 male patients with stress urinary incontinence underwent artificial urinary sphincter procedures from 1983 to 2011 at our institution, of which 1,082 were primary placements. Of these patients 125 experienced mechanical device malfunction. Multiple clinical and surgical variables were evaluated for a potential association with device malfunction. In addition, we evaluated for predictors of failure of the revised device, including time from primary artificial urinary sphincter to revision surgery and surgical revision strategy (single component vs entire device), with failure defined as any tertiary surgery. RESULTS: At a median followup of 4.2 years (IQR 0.8, 7.9) 125 patients experienced device malfunction. The urethral cuff was the most common component failure (46.1%), followed by abdominal reservoir (22.6%), tubing (21.7%) and pump (9.6%). There was no association of time from primary surgery to revision for mechanical failure (HR 0.89, p=0.33) or revision strategy (HR 0.47, p=0.15) with the risk of tertiary surgery. Additionally, as there was no significant interaction between these variables (HR 1.11, p=0.39), no cutoff could be identified at which one revision technique produced significantly improved device survival compared to another. However, there was a trend toward improved 3-year device survival after replacement of the entire device vs a single component (76% vs 60%, p=0.11). CONCLUSIONS: No cutoff in time to mechanical failure could be identified to guide decision making in the management of mechanical artificial urinary sphincter failure. Likewise, it is unclear if replacing the entire device, rather than the single malfunctioning component, alters device survival. As such, further studies are needed. However, given the current trend toward improved overall device survival, the limited additional risk and the lack of adequate clinical predictors for tertiary surgery, we would advocate for replacement of the entire device when possible.

Standardizing the Definition of Biochemical Recurrence after Radical Prostatectomy-What Prostate Specific Antigen Cut Point Best Predicts a Durable Increase and Subsequent Systemic Progression?

PURPOSE: Multiple definitions of biochemical recurrence for prostate cancer exist after radical prostatectomy, and variation continues in prostate cancer outcome reporting and secondary treatment initiation. We reviewed long-term prostatectomy outcomes to assess the most appropriate prostate specific antigen cut point that predicts future disease progression. MATERIALS AND METHODS: We identified 13,512 patients with cT1-2N0M0 prostate cancer who underwent radical prostatectomy between 1987 and 2010. Single prostate specific antigen cut points of 0.2, 0.3, 0.4 and 0.5 ng/ml or greater, as well as confirmatory prostate specific antigen value definitions of 0.2 ng/ml or greater followed by prostate specific antigen greater than 0.2 ng/ml and 0.4 ng/ml or greater followed by prostate specific antigen greater than 0.4 ng/ml were tested. Continued prostate specific antigen increase after a designated cut point definition was estimated using cumulative incidence. The strength of association between biochemical recurrence definitions and subsequent systemic progression were analyzed using Cox proportional hazard models and the O'Quigley event based R(2) test. RESULTS: At a median postoperative followup of 9.1 years (IQR 4.9-14.3) a detectable prostate specific antigen developed in 5,041 patients and systemic progression developed in 512. After reaching the prostate specific antigen cut point of 0.2, 0.3 and 0.4 ng/ml, the percentage of patients experiencing a continued prostate specific antigen increase over 5 years was 61%, 67% and 74%, respectively, plateauing at 0.4 ng/ml. The strongest association between biochemical recurrence and systemic progression occurred using a single prostate specific antigen cut point of 0.4 ng/ml or greater (HR 36, R(2) 0.92). CONCLUSIONS: A prostate specific antigen cut point of 0.4 ng/ml or greater reflects the threshold at which a prostate specific antigen increase becomes durable and shows the strongest correlation with subsequent systemic progression. Consideration should be given to using a prostate specific antigen of 0.4 ng/ml or greater as the standard biochemical recurrence definition after radical prostatectomy.

Evaluation of pT0 prostate cancer in patients undergoing radical prostatectomy.

OBJECTIVE: To evaluate the incidence, predictors and oncological outcomes of pT0 prostate cancer (PCa). METHODS: We conducted a retrospective analysis of 20 222 patients undergoing radical prostatectomy (RP) for PCa at the Mayo Clinic between 1987 and 2012. Disease recurrence was defined as follow-up PSA >0.4 ng/mL or biopsy-proven local recurrence. Systemic progression was defined as development of metastatic disease on imaging. Comparisons of baseline characteristics between pT0 and non-pT0 groups were carried out using chi-squared tests. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 62 patients (0.3%) had pT0 disease according to the RP specimen. In univariable analysis, pT0 disease was significantly associated with older age (P = 0.045), lower prostate-specific antigen (PSA; P = 0.002), lower clinical stage (P < 0.001), lower biopsy Gleason score (P = 0.042), and receipt of preoperative transurethral resection, hormonal and radiation therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower Gleason score, and receipt of preoperative treatment were independently associated with pT0 (all P < 0.05). Seven patients (11%) with pT0 PCa developed disease recurrence over a median follow-up of 10.9 years. All seven patients had preoperative treatment(s) and three had recurrence with a PSA doubling time of <9 months. Compared with non-pT0 disease, pT0 disease was associated with longer recurrence-free survival (P < 0.05). Only one (1.6%) patient with pT0 disease developed systemic progression. CONCLUSIONS: pT0 stage PCa is a rare phenomenon and is associated with receipt of preoperative treatment and features of low-risk PCa. Although pT0 has a very favourable prognosis, some men, especially those who received preoperative treatment, experience a small but non-negligible risk of disease recurrence and systemic progression.

Impact of a family history of prostate cancer on clinicopathologic outcomes and survival following radical prostatectomy.

PURPOSE: While a family history (FH) of prostate cancer represents an established risk factor for prostate cancer diagnosis, conflicting data exist regarding the oncologic importance of FH. Herein, we evaluated the association of FH with clinicopathologic outcomes among men undergoing radical prostatectomy (RP). METHODS: We identified 16,472 men who underwent RP between 1987 and 2010 at Mayo Clinic. Patients were considered to have a positive FH if at least one first-degree relative had been diagnosed with prostate cancer. Survival was estimated using the Kaplan-Meier method. The associations of FH with clinicopathologic features and survival were evaluated using logistic and Cox regression analyses. RESULTS: Overall, 5323 (32.3 %) men reported a FH of prostate cancer. Median follow-up was 9.9 years (IQR 5.9, 15.5). Patients with a FH were significantly more likely to have low-risk disease (47.7 vs. 43.0 %; p < 0.0001) and were significantly more likely to have organ-confined disease at RP (79.2 vs. 74.4 %; p < 0.0001). Men with FH had a significantly higher 10-year cancer-specific (99 vs. 97 %; p < 0.001) and overall survival (92 vs. 85 %; p < 0.001) than men without FH. Moreover, on multivariable analysis, FH of prostate cancer remained independently associated with reduced cancer-specific (HR 0.68; p = 0.003) and all-cause mortality (HR 0.69; p < 0.0001). CONCLUSION: In this surgical population, FH of prostate cancer was associated with lower-risk disease at diagnosis, more favorable pathology at RP, and significantly better cancer-specific and overall survival. These results may be utilized for patient counseling.

Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials.

The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over ≥6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log2HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.

Outcomes of artificial urinary sphincter placement in octogenarians.

OBJECTIVE: To evaluate the impact of patient age on device outcomes among patients undergoing primary artificial urinary sphincter. METHODS: A total of 1081 male patients who underwent primary artificial urinary sphincter placement from 1983 to 2011 were analyzed, including 91 men (8%) who were aged >80 years at the time of surgery. Revisions and explanations were compared between men stratified by decade of life. Hazard ratios adjusting for competing risks were used to determine the association with age and artificial urinary sphincter device outcomes (infection/erosion, urethral atrophy and malfunction), while overall device failure was estimated using Kaplan-Meier and Cox regression analysis. RESULTS: Patients aged >80 years were more likely to have coronary disease (P = 0.009), diabetes mellitus (P = 0.04), hypertension (P = 0.002) and lower body mass index (P < 0.0001). On multivariable analysis, patients aged >80 years were significantly more likely to experience device erosion or infection compared with a reference of patients aged <60 years (hazard ratio 4.13; P = 0.046), whereas there was no difference in those patients aged 60-70 years or 70-80 years compared with the reference group (P = 0.56 and 0.45). There was no significant difference in overall device survival between the age-stratified groups (P = 0.26). CONCLUSIONS: Although overall artificial urinary sphincter device survival is similar, patients aged >80 years are more likely to experience erosion or infection compared with younger patients. Despite this, the overall device failure rate is low, and artificial urinary sphincter might be considered for appropriately selected and counseled octogenarians.

Perioperative Complications following Artificial Urinary Sphincter Placement.

PURPOSE: We evaluated perioperative complications in patients undergoing primary artificial urinary sphincter placement and the potential impact of these complications on device outcomes. MATERIALS AND METHODS: During the 2-year period from 2012 to 2014 we retrospectively evaluated the outcomes of 197 consecutive artificial urinary sphincter implantation procedures performed at our institution for post-prostatectomy incontinence. Of these cases 100 that were primary implantations comprise the study cohort. Perioperative complications, defined as those occurring within 6 weeks postoperatively, were classified by the Clavien-Dindo classification. After office evaluation at 6 weeks patients were followed for symptoms. Patient followup was obtained through office examination and telephone correspondence. RESULTS: Patients undergoing primary artificial urinary sphincter implantation had a median age of 71.5 years (IQR 66, 76). The overall rate of any complication (Clavien I-V) within 6 weeks of surgery was 35%, including urinary retention in 31% of cases, cellulitis in 1%, device infection in 2% and urethral erosion in 2%. No significant differences in pertinent clinical comorbidities such as age (p = 0.69), hypertension (p = 0.95), coronary artery disease (p = 0.57), diabetes mellitus (p = 0.17), body mass index (p = 0.47), prior pelvic radiation therapy (p = 0.45), prior urethral sling placement (p = 0.91) or transcorporeal urethral cuff placement (p = 0.22) were found between patients with and without complications. Median followup was similar between those with and without postoperative urinary retention (p = 0.14). Postoperative urinary retention was associated with adverse 6-month device survival (76% vs 89%, p = 0.04). CONCLUSIONS: The most common complication of artificial urinary sphincter placement is urinary retention. Serious adverse events following artificial urinary sphincter placement are rare. Postoperative urinary retention is associated with adverse short-term device survival rates.