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We assessed whether Prostate Health Index results improve prediction of grade reclassification for men on active surveillance.We identified men in Canary Prostate Active Surveillance Study with Grade Group 1 cancer. Outcome was grade reclassification to Grade Group 2+ cancer. We considered decision rules to maximize specificity with sensitivity set at 95%. We derived rules based on clinical data (RWe included 1,532 biopsies (n = 610 discovery; n = 922 validation) among 1,142 men. Grade reclassification was seen in 27% of biopsies (23% discovery, 29% validation). Among the discovery set, at 95% sensitivity, RAmong active surveillance patients, using Prostate Health Index with clinical data modestly improved prediction of grade reclassification on confirmatory biopsy and did not improve prediction on subsequent biopsies.

Clinical trials require significant resources, but benefits are only realized after trial completion and dissemination of results. We comprehensively assessed early discontinuation, registry results reporting, and publication by trial sponsor and subspecialty in urology trials.We assessed trial registrations from 2007 to 2019 on ClinicalTrials.gov and publication data from PubMed®/MEDLINE®. Associations between sponsor or subspecialty with early discontinuation were assessed using Cox proportional hazards and results reporting or publication with logistic regression at 3 years after completion.Of 8,636 trials 3,541 (41.0%) were completed and 999 (11.6%) were discontinued. Of completed trials 26.9% reported results and 21.6% were published. Sponsors included academic institutions (53.1%), industry (37.1%) and the U.S. government (9.8%). Academic-sponsored (adjusted HR 0.81, 95% CI 0.69-0.96, p=0.012) and government-sponsored trials (adjusted HR 0.62, 95% CI 0.49-0.78, p0.001) were less likely than industry to discontinue early. Government-sponsored trials were more likely to report (adjusted OR 1.72, 95% CI 1.17-2.54, p=0.006) and publish (adjusted OR 1.89, 95% CI 1.23-2.89, p=0.004). Academic-sponsored trials were less likely to report (adjusted OR 0.65, CI:0.48-0.88, p=0.006) but more likely to publish (adjusted OR 1.72, 95% CI 1.25-2.37, p0.001). These outcomes were similar across subspecialties. However, endourology was more likely to discontinue early (adjusted HR 2.00, 95% CI 1.53-2.95, p0.001), general urology was more likely to report results (adjusted OR 1.54, 95% CI 1.13-2.11, p=0.006) and andrology was less likely to publish (adjusted OR 0.53, 95% CI 0.35-0.81, p=0.003).Sponsor type is significantly associated with trial completion and dissemination. Government-sponsored trials had the best performance, while industry and academic-sponsored trials lagged in completion and results reporting, respectively. Subspecialty played a lesser role. Lack of dissemination remains a problem for urology trials.

Patients with kidney cancer are at risk for chronic kidney disease after radical and partial nephrectomy. We determined if the urine albumin-to-creatinine ratio is independently associated with progressive chronic kidney disease after nephrectomy.We performed a cohort study based within a large, integrated health care system. We identified patients who underwent radical or partial nephrectomy from 2004 to 2014 with urine albumin-to-creatinine ratio measured in the 12 months before surgery. We fit multivariable models to determine if the urine albumin-to-creatinine ratio was associated with the time to chronic kidney disease progression (defined as reaching stage 4 or 5 chronic kidney disease, estimated glomerular filtration rate less than 30 ml/minute/1.73 mA total of 1,930 patients underwent radical or partial nephrectomy and had preoperative urine albumin-to-creatinine ratio and preoperative and postoperative estimated glomerular filtration rate. Of these patients 658 (34%) and 157 (8%) had moderate (urine albumin-to-creatinine ratio 30 to 300 mg/gm) or severe albuminuria (urine albumin-to-creatinine ratio greater than 300 mg/gm), respectively. Albuminuria severity was independently associated with progressive chronic kidney disease after radical (moderate albuminuria HR 1.7, 95% CI 1.4-2.2; severe albuminuria HR 2.3, 95% CI 1.7-3.1) and partial nephrectomy (moderate albuminuria HR 1.8, 95% CI 1.2-2.7; severe albuminuria HR 4.3, 95% CI 2.7-7.0). Albuminuria was also associated with survival following radical and partial nephrectomy.In patients undergoing radical or partial nephrectomy the severity of albuminuria can stratify risk of progressive chronic kidney disease.

INTRODUCTION AND OBJECTIVE:For patients diagnosed with muscle invasive bladder cancer, baseline kidney function plays a significant role in selecting chemotherapy regimens and the type of urinary r...

Outcomes in patients who enroll in active surveillance programs for prostate cancer while receiving 5α-reductase inhibitors have not been well defined. We sought to determine the association of 5α-reductase inhibitor use with the risk of reclassification in the PASS (Canary Prostate Active Surveillance Study).Participants in the multicenter PASS were enrolled between 2008 and 2016. Study inclusion criteria were current or never 5α-reductase inhibitors use, Gleason score 3 + 4 or less prostate cancer at diagnosis, less than a 34% core involvement ratio at diagnosis and 1 or more surveillance biopsies. Included in study were 1,009 men, including 107 on 5α-reductase inhibitors and 902 who had never received 5α-reductase inhibitors. Reclassification was defined as increase in the Gleason score and/or an increase to 34% or greater in the ratio of biopsy cores positive for cancer. Adverse pathology at prostatectomy was defined as Gleason 4 + 3 or greater and/or nonorgan confined disease (pT3 or N1).On multivariable analysis there was no difference in reclassification between men who had received and those who had never received 5α-reductase inhibitors (HR 0.81, p = 0.31). Patients who had received 5α-reductase inhibitors were less likely to undergo radical prostatectomy (8% vs 18%, p = 0.01) or any definitive treatment (19% vs 24%, p = 0.04). In the 167 participants who underwent radical prostatectomy there was no suggestion of a difference in the rate of adverse pathology findings at prostatectomy between 5α-reductase inhibitor users and nonusers.Continued 5α-reductase inhibitor use after an initial diagnosis of prostate cancer was not associated with the risk of reclassification on active surveillance in men in the PASS cohort.

We sought to characterize the effects of prostate specific antigen registry errors on clinical research by comparing cohorts based on cancer registry prostate specific antigen values with those based directly on results in the electronic health record.We defined sample cohorts of men with prostate cancer using data from the Veterans Health Administration, including those with a prostate specific antigen value less than 4.0, 4.0 to 10.0, 10.0 to 20.0 and 20.0 to 98.0 ng/ml, respectively. We compared the composition of each cohort and overall patient survival when using prostate specific antigen values from the Veteran Affairs Central Cancer Registry vs the gold standard electronic health record laboratory file results.There was limited agreement among cohorts when defined by cancer registry prostate specific antigen values vs the laboratory file of the electronic health record. The least agreement of 58% was seen in patients with prostate specific antigen less than 4.0 ng/ml and greatest agreement of 89% was noted among patients with prostate specific antigen between 4.0 and 10.0 ng/ml. In each cohort patients assigned to a cohort based only on the cancer registry prostate specific antigen value had significantly different overall survival when compared with patients assigned based on registry and laboratory file prostate specific antigen values.Cohorts based exclusively on cancer registry prostate specific antigen values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes.

Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Data suggest a higher risk of testicular cancer in infertile men. However, the relationship between infertility and other cancers remains uncertain.We analyzed subjects from the Truven Health MarketScan® claims database from 2001 to 2009. Infertile men were identified through diagnosis and treatment codes. Comparison groups were created of men who underwent vasectomy and a control cohort of men who were not infertile and had not undergone vasectomy. The incidence of cancer was compared to national U.S. estimates. Infertile men were also compared to men who underwent vasectomy and the control cohort using a Cox regression model.A total of 76,083 infertile men were identified with an average age of 35.1 years. Overall 112,655 men who underwent vasectomy and 760,830 control men were assembled. Compared to age adjusted national averages, infertile, vasectomy and control subjects in the study cohorts had higher rates of all cancers and many individual cancers. In time to event analysis, infertile men had a higher risk of cancer than those who underwent vasectomy or controls. Infertile men had a higher risk of testis cancer, nonHodgkin lymphoma and all cancers than the vasectomy and control groups.Consistent with prior reports, we identified an increased risk of testicular cancer in infertile men. The current data also suggest that infertile men are at an increased risk of all cancers in the years after infertility evaluation. Future research should focus on confirming these associations and elucidating pathways between infertility and cancer.

Asian-American men with prostate cancer have been reported to present with higher grade and later stage disease than white American men. However, Asian-American men comprise a heterogeneous population with distinct health outcomes. We compared prostate cancer risk profiles among the diverse racial and ethnic groups in California.We used data from the California Cancer Registry on 90,845 nonHispanic white, nonHispanic black and Asian-American men diagnosed with prostate cancer between 2004 and 2010. Patients were categorized into low, intermediate and high risk groups based on clinical stage, Gleason score and prostate specific antigen at diagnosis. Using polytomous logistic regression we estimated adjusted ORs for the association of race/ethnicity and nativity with risk group.In addition to the nonHispanic black population, 6 Asian-American groups (United States born Chinese, foreign born Chinese, United States born Japanese, foreign born Japanese, foreign born Filipino and foreign born Vietnamese) were more likely to have an unfavorable risk profile compared to nonHispanic white men. The OR for high vs intermediate risk disease ranged from 1.23 (95% CI 1.02-1.49) for United States born Japanese men to 1.45 (95% CI 1.31-1.60) for foreign born Filipino men. These associations appeared to be driven by higher grade and prostate specific antigen rather than by advanced clinical stage at diagnosis.In this large, ethnically diverse, population based cohort Asian-American men were more likely to have an unfavorable risk profile at diagnosis. This association varied by racial/ethnic group and nativity, and was not attributable to later stage at diagnosis. This suggests that Asian men may have biological differences that predispose to more severe disease.

Prior radical prostatectomy series have shown an inverse association between prostate size and high grade cancer. It has been suggested that smaller size prostates arise in a low androgen environment, enabling development of more aggressive cancer. We propose that this observation is the result of ascertainment bias driven by prostate specific antigen performance.We identified 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (723) and T2 (681) disease who underwent surgery between 1988 and 2002, and underwent detailed morphometric mapping by a single pathologist. Multivariate linear regression was performed to assess for the effects of age, prostate weight and prostate specific antigen on total and high grade (Gleason grade 4/5) cancer volume and percentage of high grade disease.In patients who underwent biopsy due to abnormal prostate specific antigen (stage T1c), prostate weight was negatively associated (p = 0.0002) with total cancer volume, volume of high grade disease and percentage of high grade disease. For patients who underwent biopsy based on abnormal digital rectal examination (stage T2) these associations were not observed.Improved prostate specific antigen performance for high grade disease results in ascertainment bias in patients with T1c disease. Thus, the association between prostate size and high grade disease may be a consequence of grade dependent performance of prostate specific antigen rather than true tumor biology.

It is now apparent that multiple genetic alterations, including oncogene activation and tumor suppressor gene inactivation, are necessary steps in carcinogenesis. We have studied this concept in renal cancers by looking at specific tumor suppressor genes implicated in several allelotyping studies. Primary, predominantly low stage renal tumors of varying grades and histologic subtypes were investigated for allelic loss of 3p, 17p and the p53 gene, the DCC gene and the Rb gene and its product. 3p loss occurred in 47% of tumors studied and was much more common in clear cell cancers (85%). 17p and p53 gene loss were relatively uncommon events with only 6 of 42 tumors demonstrating loss. None of the tumors with typical histologies had allelic loss of the DCC gene, though loss did occur in leiomyosarcoma and a collecting duct tumor. Allelic loss of the Rb gene occurred in one clear cell tumor, the leiomyosarcoma, and, interestingly, in both collecting duct tumors in this series. Allelic loss of the Rb gene was correlated with little or no RB protein expression as judged by immunohistochemistry. At all loci studied, allelic loss did not appear to correlate with tumor grade or stage. These results suggest that inactivation of the p53, Rb, and DCC genes by allelic loss are uncommon events in the early stages of renal carcinogenesis.

A 1.5 cm. tubularized neourethra was formed using an anterior bladder flap as part of bladder neck reconstruction after radical retropubic prostatectomy in 69 consecutive patients with clinically localized prostate cancer (study group). Postoperative continence (defined as requiring no protection for any activity) was assessed by history at 3 months (all men) and 6 months (45 of 69 men). Continence in the study group was compared to that of 45 men with 6 months of followup who underwent radical retropubic prostatectomy without tubularization of the anterior bladder (control group). At 3 months 38 of 69 men (55%) were continent in the study group and 14 of 45 (31%) were continent in the control group (p0.03). At 6 months 39 of 45 men (87%) were continent in the study group compared to 21 of 45 (47%) in the control group (p0.01). Upright cystograms performed on men with and without the tubularized neourethra after radical retropubic prostatectomy suggest that a neourethra proximal to the external sphincter may increase resistance in this area and result in early return of urinary control in men undergoing radical retropubic prostatectomy.