The Cardiovascular Safety of Five-Alpha-Reductase Inhibitors Among Men with Benign Prostatic Hyperplasia: A Population-Based Cohort Study.

BACKGROUND: Five-alpha reductase inhibitors (5αRIs) are used to treat benign prostatic hyperplasia (BPH). However, the cardiovascular effects of 5αRIs remain poorly understood. The study objective was to compare the rate of hospitalization for heart failure among men with BPH prescribed 5αRIs to that of men with BPH not prescribed BPH medications. METHODS: Using the Clinical Practice Research Datalink linked with hospitalization and vital statistics data, we conducted a population-based cohort study among patients newly diagnosed with BPH. We defined exposure as the current use of 5αRIs, current use of alpha-blockers, and no current use of BPH medications in a time-varying approach. The primary endpoint was hospitalization for heart failure, and secondary endpoints were myocardial infarction, stroke, and cardiovascular death. We used time-dependent Cox-proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Our cohort included 94,440 men with incident BPH. A total of 3893 hospitalizations for heart failure occurred over 527,660 person-years of follow-up (incidence rate 7.38; 95% CI, 7.15-7.61, per 1000 person-years). Compared with no current use of BPH medications, current use of 5αRIs was not associated with an increased risk of hospitalization for heart failure (HR 0.94; 95% CI, 0.86-1.03), myocardial infarction (HR 0.92; 95% CI, 0.81-1.05), stroke (HR 0.94; 95% CI, 0.85-1.05), or cardiovascular death (HR 0.89; 95% CI, 0.80-0.99). CONCLUSIONS: The use of 5αRIs was not associated with an increased risk of hospitalization for heart failure, myocardial infarction, stroke, or cardiovascular death compared with non-use.

Trends in the pharmacological treatment of benign prostatic hyperplasia in the UK from 1998 to 2016: a population-based cohort study.

PURPOSE: To describe trends in the pharmacological treatment of BPH in the United Kingdom (UK) from 1998 to 2016. METHODS: We created a cohort of men with a diagnosis of BPH between 1998 and 2016 using the Clinical Practice Research Datalink. Using Poisson regression, we estimated annual prescription rates of 5αRIs, α-blockers, and combination therapy (5αRIs + α-blockers). Adherence was defined by a proportion of days covered > 80%. RESULTS: Our cohort included 192,640 men with BPH who generated 1,176,264 person-years (PYs) of follow-up. The mean age was 68.0 (standard deviation: 10.7) years. The prescription rate of all BPH medications during the study period was 347.6 per 100 PYs (95% CI 347.2-347.9). α-Blockers had the highest prescription rate (222.9 per 100 PYs, 95% CI 222.7-223.2); prescription rates of 5αRIs and combination therapy were 69.1 per 100 PYs (95% CI 69.0-69.3) and 55.5 per 100 PYs (95% CI 55.4-55.7), respectively. The prescription rate for combination therapy was 19 times greater in 2013-2016 than in 1998-2000 (rate ratio: 19.2, 95% CI 18.6-19.7), while the prescription rates for 5αRIs and α-blockers each doubled during this period (rate ratio: 1.86, 95% CI 1.84-1.88 and rate ratio: 2.02, 95% CI 2.01-2.04, respectively). The proportion of patients who were adherent at 1 year to 5αRIs (32.3%), α-blockers (44.0%), and combination therapy (45.6%) was low. CONCLUSION: The prescription rate of BPH medications increased substantially between 1998 and 2016 in the UK, with the greatest relative increase observed with combination therapy. Adherence to BPH medications was low in this population-based study.

Does surgical delay for radical prostatectomy affect patient pathological outcome? A retrospective analysis from a Canadian cohort.

INTRODUCTION: We sought to assess the impact of surgical wait time (SWT) to robot-assisted radical prostatectomy (RARP) on final pathological outcome. METHODS: A retrospective review of RARP patient records operated between 2006 and 2015 was conducted. SWT was defined as period from prostate biopsy to surgery. Primary outcome was the impact on postoperative Cancer of the Prostate Risk Assessment (CAPRA-S) score. Patients were stratified according to D'Amico risk categories. Univariate analysis (UVA) and multivariable (MVA) analysis with a generalized linear model was used to evaluate the effect of SWT and other predictive factors on pathological outcome in individual risk group and on the overall sample. RESULTS: A total of 835 patients were eligible for analysis. Mean SWT was significantly different between the three D'Amico groups, with mean SWT of 180.22 days (95% confidence interval [CI] 169.03; 191.41), 159.14 days (95% CI 152.38; 165.90), and 138.96 days (95% CI 124.60; 153.33) for low-, intermediate-, and high-risk groups, respectively (p<0.001). After stratification by D'Amico risk group, no significant association was observed between SWT and CAPRA-S score in the three risk categories on UVA and MVA. Predictors of higher CAPRA-S score in the multivariable model in the overall cohort were: older age (p=0.014), biopsy Gleason score (p<0.001), percentage of positive cores (p<0.001), and clinical stage (p<0.001). CONCLUSIONS: In the present study evaluating SWT for RARP in a Canadian socialized system, increased delay for surgery does not appear to impact the pathological outcome. Further studies are required to evaluate the impact of wait time on biochemical recurrence-free survival, cancer-specific survival, and overall survival.

Erectile function recovery after robotic-assisted radical prostatectomy (RARP): long term exhaustive analysis across all preoperative potency categories.

INTRODUCTION: To evaluate erectile function recovery following robotic-assisted radical prostatectomy (RARP) according to preoperative sexual health inventory for men (SHIM) score stratification. MATERIALS AND METHODS: We prospectively collected data on 250 consecutive patients who underwent RARP by a single surgeon between October 2006 and October 2012. Thirty-six patients were excluded because of lack of preoperative SHIM score. All patients had a minimum follow up of 2 years. Patients were divided into four groups according to their preoperative SHIM score: group 1 with normal potency (SHIM 22-25), group 2 with mild ED (SHIM 17-21), group 3 with mild-moderate ED (SHIM 12-16) and group 4 with moderate-severe ED (SHIM 1-11). Patients were followed at 3, 6, 9, 12, 18, 24 months intervals and twice yearly thereafter. SHIM questionnaire and erection hardness scale (EHS) score were collected at each visit. Potency was defined as successful penetration during intercourse (EHS score 3-4) with or without phosphodiesterase type 5-inhibitor (PDE5-I). RESULTS: After exclusion, 214 patients were evaluated. The number of patients in group 1, 2, 3 and 4 were 95, 59, 26 and 34, respectively. At 3, 6, 9, 12, 18, 24 months, SHIM scores and potency rates were statistically different between groups 1 versus 2 versus 3 versus 4 (p < 0.01, at each time point). Patients in each group 1, 2 and 3 showed a statistically significant improvement in potency rates and SHIM scores at consecutive follow up visits up to 24 months (p < 0.01, for each potency group). Potency rates at 24 months for groups 1 to 4 were 83.3%, 54.5%, 50.0%, and 20.7%, respectively (p < 0.001). CONCLUSION: For proper patient counseling and better prediction of erectile function recovery after RARP, it is important to stratify patients according to preoperative SHIM scores. Setting realistic expectations may increase patient satisfaction.

Uroflow Stop Test and Potency Recovery: A Surrogate for Pelvic Floor Integrity Post Robotic-Assisted Radical Prostatectomy?

OBJECTIVE: To study the relation between uroflow Stop Test and early recovery of potency following robot-assisted radical prostatectomy (RARP). We recently showed that the ability to completely stop urine flow during voiding, measured objectively by uroflowmetry at the time of catheter removal (uroflow Stop Test) can predict early urinary continence recovery following RARP. MATERIALS AND METHODS: In this prospective observational cohort, data were collected on 108 patients operated by a single surgeon (AEH). Eighty patients had a positive uroflow Stop Test (group one) and 28 had a negative Stop Test (group two). Patients were followed for a minimum of 2 years. Covariates included age, body mass index, international prostate symptom score and sexual health inventory for men scores, prostate-specific antigen, tumor stage, prostate volume, nerve sparing status, and estimated blood loss. RESULTS: Preoperative characteristics were comparable between both groups except nerve sparing and prostate-specific antigen which were statistically higher in group one (P <.05). Early 3- and 6-months recovery of erectile function was significantly higher in group one. Potency rates in group one and two at 1, 3, 6, 9, 12, 18, and 24 months were 25% vs 14.3% (P = .241), 54.5% vs 18.5% (P = .001), 55.4% vs 18.5% (P = .001), 56.4% vs 36% (P = .084), 66.6% vs 50% (P = .141), 65.5% vs 56% (P = .404) and 73.2% vs 57.7% (P = .160) respectively. Uroflow Stop Test was independent predictor of early potency recovery on multivariate regression analysis at 6 months [odds ratio 6.042 (confidence interval 95% 1.496-24.413) P = .012]. CONCLUSION: Uroflow Stop Test is simple and can help predict early potency recovery following RARP.

5α-Reductase Inhibitors and the Risk of Cancer-Related Mortality in Men With Prostate Cancer.

IMPORTANCE: 5α-Reductase inhibitors (5-ARIs) are widely used in the treatment of benign prostatic hyperplasia. However, randomized clinical trials have raised concerns that their use may be associated with an increased risk of high-grade prostate cancer tumors that would ultimately lead to worse prostate cancer outcomes. To date, few observational studies have addressed this important safety concern. OBJECTIVE: To determine whether the use of 5-ARIs before prostate cancer diagnosis is associated with an increased risk of cancer-specific and all-cause mortality in men with a new diagnosis of prostate cancer in the real-world setting. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted in a cohort of 13,892 men with a new diagnosis of prostate cancer between January 1, 1999, and December 31, 2009, who were followed up until October 1, 2012. Patients were individually linked across 4 databases from the United Kingdom: National Cancer Data Repository, Clinical Practice Research Datalink, Hospital Episodes Statistics database, and Office for National Statistics database. MAIN OUTCOMES AND MEASURES: Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs of prostate cancer-specific and all-cause mortality associated with prediagnostic use of 5-ARIs. For each outcome, 2 models were constructed, one adjusted for predefined covariates (conventional model) and another adjusted for high-dimensional propensity score (HD-PS) deciles. RESULTS: During a mean (SD) of 4.5 (3.1) years, 5001 deaths occurred, including 2429 from prostate cancer (crude incidence rate of 3.86 per 100 person-years [95% CI, 3.71-4.02]). In the conventional model, use of 5-ARIs before prostate cancer diagnosis was not associated with an increased risk of prostate cancer-specific mortality (crude incidence rates, 3.76 [95% CI, 3.04-4.59] [use] vs 3.87 [95% CI, 3.71-4.03] [nonuse] per 100 person-years; adjusted hazard ratio [aHR], 0.86 [95% CI, 0.69-1.06]) and all-cause mortality (crude incidence rates, 8.42 [95% CI, 7.32-9.64] [use] vs 7.93 [95% CI, 7.71-8.16] [nonuse] per 100 person-years; aHR, 0.87; 95% CI, 0.75-1.00). Similar results were observed with the HD-PS adjusted model (prostate cancer-specific mortality: aHR, 0.90 [95% CI, 0.73-1.13]; and all-cause mortality: aHR, 0.92 [95% CI, 0.80-1.07]). CONCLUSIONS AND RELEVANCE: The use of 5-ARIs was not associated with an increased risk of prostate cancer-specific and all-cause mortality in men with a new diagnosis of prostate cancer. While these results provide reassurance, additional studies are needed to replicate these findings.

Oncological and functional outcomes of 722 robot-assisted radical prostatectomy (RARP) cases: The largest Canadian 5-year experience.

INTRODUCTION: While RARP (robotic-assisted radical prostatectomy) has become the predominant surgical approach to treat localized prostate cancer, there is little Canadian data on its oncological and functional outcomes. We describe the largest RARP experience in Canada. METHODS: Data from 722 patients who underwent RARP performed by 7 surgeons (AEH performed 288, TH 69, JBL 23, SB 17, HW 15, QT 7, and KCZ 303 patients) were collected prospectively from October 2006 to December 2013. Preoperative characteristics, as well as postoperative surgical and pathological outcomes, were collected. Functional and oncological outcomes were also assessed up to 72 months postoperative. RESULTS: The median follow-up (Q1-Q3) was 18 months (9-36). The D'Amico risk stratification distribution was 31% low, 58% intermediate and 11% high-risk. The median operative time was 178 minutes (142-205), blood loss was 200 mL (150-300) and the postoperative hospital stay was 1 day (1-23). The transfusion rate was only 1.0%. There were 0.7% major (Clavien III-IV) and 10.1% minor (Clavien I-II) postoperative complications, with no mortality. Pathologically, 445 men (70%) were stage pT2, of which 81 (18%) had a positive surgical margin (PSM). In addition, 189 patients (30%) were stage pT3 and 87 (46%) with PSM. Urinary continence (0-pads/day) returned at 3, 6, and 12 months for 68%, 80%, and 90% of patients, respectively. Overall, the potency rates (successful penetration) for all men at 6, 12, and 24 months were 37%, 52%, and 59%, respectively. Biochemical recurrence was observed in 28 patients (4.9%), and 14 patients (2.4%) were referred for early salvage radiotherapy. In total, 49 patients (8.4%) underwent radio-therapy and/or hormonal therapy. CONCLUSIONS: This study shows similar results compared to other high-volume RARP programs. Being the largest RARP experience in Canada, we report that RARP is safe with acceptable oncologic outcomes in a Canadian setting.

Use of statins and the risk of death in patients with prostate cancer.

PURPOSE: To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. PATIENTS AND METHODS: A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. RESULTS: During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). CONCLUSION: Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.

Androgen deprivation therapy and risk of acute kidney injury in patients with prostate cancer.

IMPORTANCE: The use of androgen deprivation therapy (ADT) in the treatment of advanced prostate cancer has been shown to delay the clinical progression of the disease. However, the testosterone suppression associated with this therapy may lead to a hypogonadal condition that can have detrimental effects on renal function, thus raising the hypothesis that ADT-induced hypogonadism could potentially lead to acute kidney injury (AKI). OBJECTIVE: To determine whether the use of ADT is associated with an increased risk of AKI in patients newly diagnosed with prostate cancer. DESIGN AND SETTING: A nested case-control analysis using medical information extracted from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. PARTICIPANTS: Men newly diagnosed with nonmetastatic prostate cancer between January 1, 1997, and December 31, 2008, were selected and followed up until December 31, 2009. Cases were patients with incident AKI during follow-up who were randomly matched with up to 20 controls on age, calendar year of prostate cancer diagnosis, and duration of follow-up. MAIN OUTCOMES AND MEASURES: Conditional logistic regression was used to estimate odds ratios (ORs) with 95% CIs of AKI associated with the use of ADT. ADT was categorized into 1 of 6 mutually exclusive groups: gonadotropin-releasing hormone agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, estrogens, and combination of the above. RESULTS A total of 10,250 patients met the study inclusion criteria. During a mean follow-up of 4.1 (SD, 2.9) years, 232 incident cases of AKI were identified (rate, 5.5/1000 person-years). Overall, current use of any ADT was associated with an increased risk of AKI when compared with never use (OR, 2.48 [95% CI, 1.61-3.82]), generating a rate difference of 4.43/1000 persons per year (95% CI, 1.54-7.33). This association was mainly driven by a combined androgen blockade consisting of gonadotropin-releasing hormone agonists with oral antiandrogens (OR, 4.50 [95% CI, 2.61-7.78]), estrogens (OR, 4.00 [95% CI, 1.06-15.03]), other combination therapies (OR, 4.04 [95% CI, 1.88-8.69]), and gonadotropin-releasing hormone agonists (OR, 1.93 [95% CI, 1.20-3.10]). CONCLUSIONS AND RELEVANCE: In a cohort of patients with newly diagnosed nonmetastatic prostate cancer, the use of ADT was significantly associated with an increased risk of AKI. These findings require replication in other well-designed studies as well as further investigation of their clinical importance.

Androgen deprivation therapy and the risk of colorectal cancer in patients with prostate cancer.

PURPOSE: Androgens are known to play an important protective role on colorectal carcinogenesis, and thus the objective of this study was to determine whether androgen deprivation therapy (ADT) is associated with an increased risk of incident colorectal cancer in patients with prostate cancer. METHODS: We conducted a population-based cohort study within the UK General Practice Research Database population which included all patients newly diagnosed with prostate cancer between 1 January 1988 and 31 December 2008, followed until 31 December 2009. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of incident primary colorectal cancer associated with the use of ADT. Secondary analyses considered cumulative duration of use and specific ADTs. RESULTS: The cohort included a total of 21,503 patients, of whom 184 were diagnosed with colorectal cancer during a mean (SD) follow-up 4.0 (3.0) years (rate 2.4/1,000 person-years). Overall, use of ADT was not associated with an increased risk of colorectal cancer (HR 0.99, 95 % CI 0.73-1.35). Similarly, no association was observed in terms of duration use, although this secondary analysis may have been limited by statistical power. With respect to specific ADTs, bilateral orchiectomy was the only therapy associated with an increased risk of colorectal cancer (HR 2.50, 95 % CI 1.13-5.52). CONCLUSION: Overall, the use of ADT is not associated with an increased risk of incident colorectal cancer. The increased risk observed with bilateral orchiectomy may possibly be due to the prolonged androgen suppression of this therapy.

Androgen-deprivation therapy and the risk of stroke in patients with prostate cancer.

BACKGROUND: Some evidence indicates that androgen-deprivation therapy (ADT) increases the risk of diabetes and cardiovascular disease. To date, few studies have investigated whether this therapy also increases the risk of cerebrovascular events. OBJECTIVE: To determine whether different types of ADT increase the risk of stroke/transient ischaemic attacks (TIAs) in patients with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We conducted a population-based cohort study using a nested case-control analysis within the United Kingdom's General Practice Research Database population. The cohort included all patients at least 40 yr of age newly diagnosed with prostate cancer between January 1, 1988, and December 31, 2008, and followed until December 31, 2009. Cases consisted of those who experienced a first-ever stroke/TIA during follow-up. Up to 10 controls were matched to each case on age, year of cohort entry, and duration of follow-up. MEASUREMENTS: Adjusted rate ratios (RRs) of stroke/TIA associated with the use of different ADTs (gonadotropin-releasing hormone [GnRH] agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, and others) were estimated using conditional logistic regression. RESULTS AND LIMITATIONS: The cohort included 22 310 patients with prostate cancer, followed for a mean of 3.9 yr, where 938 patients experienced a first-ever stroke/TIA (rate: 10.7 per 1000/yr). Compared with nonusers of ADT, current users of GnRH agonists (adjusted RR: 1.18; 95% confidence interval [CI], 1.00-1.39), oral antiandrogens (adjusted RR: 1.47; 95% CI, 1.08-2.01), and those who underwent bilateral orchiectomy (adjusted RR: 1.77; 95% CI, 1.25-2.39) were at an increased risk of stroke/TIA. No statistically significant increased risks were observed for patients on combined androgen blockade and other ADTs, but the small numbers do not rule out a possible association. CONCLUSIONS: The results of this large population-based study provide additional evidence that different forms of ADT may increase the risk of stroke/TIA.

Screening men for prostate cancer and colorectal cancer: is practice evidence-based?

INTRODUCTION: Controversy persists about whether men should be screened for prostate cancer. On the other hand, the benefit of colorectal cancer screening has been proven for men starting at age 50. We aimed to examine the rate of exposure to previous screening tests for prostate cancer and colorectal cancer in a cohort of men living in Quebec. MATERIALS AND METHODS: As part of an event promoting early prostate cancer detection, 347 men aged 50 to 69 without an established diagnosis of prostate cancer agreed to reply to questions in a previously validated questionnaire. The self-administered questionnaire, which asked about previous screening tests for prostate cancer and colorectal cancer, was completed on-site. RESULTS: Among men aged 50 to 69, previous exposure to a digital rectal examination (DRE), a prostate-specific antigen (PSA) test, a fecal occult blood test (FOBT), and sigmoidoscopy were reported by 132 men (62.9%), 73 men (34.8%), 37 men (17.6%), and 39 men (18.6%) , respectively. Across all age strata (< 50, 50-69, > or = 70 years), PSA and DRE testing were highest in men aged 50 to 69 and were 2- to 3-fold higher than screening tests for colorectal cancer. CONCLUSIONS: In this cohort of asymptomatic Canadian men, overall and age-stratified exposure to tests to detect colon cancer early is far from ideal. Conversely, far more men have been subjected to PSA testing and DRE. Patients should be informed of the benefits and risks of colorectal cancer screening and PSA testing.

Treatment of BCG failures with intravesical BCG/Interferon: the University of Montreal experience.

OBJECTIVE: Bacillus Calmette-Guerin (BCG) has shown promise in large scale studies. We assessed recurrence-free survival in patients treated with intravesical BCG/Interferon (IFN) for non-muscle invasive, BCG refractory, transitional cell carcinoma (TCC) of the urinary bladder at our local institution. METHODS: Cancer control data were gathered for patients enrolled in a BCG/Interferon protocol at the University of Montreal. The main inclusion criteria consisted of pathologically proven evidence of intravesical BCG failure, and of complete transurethral resection of latest post BCG recurrence. Induction consisted of eight intravesical BCG/Interferon instillations. Select patients were treated with BCG/Interferon maintenance therapy. RESULTS: Thirteen patients aged from 45 to 81 years (mean: 65) were included. Stages at TCC diagnosis were distributed as follows: 6 (46%) CIS, 3 (23%) Ta, and 4 (31%) T1. Induction BCG consisted of an average of 11 weekly instillations (range 3-24). Prior to BCG/Interferon stage distribution was as follows: 9 (69%) CIS, and 4 (31%) T1. BCG/Interferon maintenance was administered to 5 (38%) patients. Follow-up ranged from 1.5 to 32 months (mean=15, median=12). Recurrence was diagnosed in 5 patients (38%). Recurrence free survival (RFS) at 24 months was 66%. When stratified according to T stage prior to BCG/IFN, patients with CIS fared worse than T1 patients (50% versus 100%). Maintenance had no effect on RFS (75% versus 69%). CONCLUSIONS: Our results corroborate previous BCG/IFN reports. In selected patients, intravesical BCG/IFN offers a valid alternative to definitive therapy.

Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer.

OBJECTIVE: To examine prostate specific-antigen (PSA) levels and percentage free/total PSA (f/tPSA) distributions as well as digital rectal examination (DRE) profiles in asymptomatic Canadian men with no established prostate cancer diagnosis, as recent data indicate that a man's risk of developing prostate cancer is higher if his baseline PSA level is above the median for his age group. SUBJECTS AND METHODS: We used data obtained during an early prostate cancer-detection event. An invitation to an onsite DRE, PSA level and f/tPSA assessment was accepted by 313 men. Serum PSA level and f/tPSA were measured before the DRE. A suspicious DRE and/or PSA level of > or = 2.5 ng/mL or f/tPSA of < or = 15% represented indications for a systematic 12-core ultrasonography-guided prostate biopsy. RESULTS: Of all the 313 men, most (235, 75%) had PSA levels of 0.01-1.53 ng/mL and an f/tPSA of >15% (285, 91.1%). The median (range) PSA level was 0.8 (0-34.2) ng/mL and f/tPSA was 27.4 (6.7-100)%. Age-specific median PSA levels and f/tPSA were, respectively, 0.7, 0.9, 1.0, 1.5 ng/mL and 31%, 27%, 26%, 25% for men aged 40-49, 50-59, 60-69 and 70-79 years. A suspicious DRE was recorded in 55 (17.6%) men, with eight (8.8%), 26 (20.0%), 14 (20.6%), and seven (28.9%) having suspicious DRE findings according to above age categories. Overall, seven (2.2%) prostate cancers were detected. CONCLUSION: The median age-specific baseline PSA levels and f/tPSA represent valuable indicators of prostate cancer risk. The population-specific baseline median PSA level should not be >1.0 ng/mL and the baseline f/tPSA should be >30%. Men with values outside of these ranges should be considered at greater risk of prostate cancer.

Normal urinary and sexual function in men without evidence of prostate cancer from Montreal, Canada.

OBJECTIVE: To examine the rates of stress urinary incontinence (SUI) and erectile dysfunction (ED), and of associated bother, in men with no evidence of prostate cancer who participated in a prostate cancer-screening event. SUBJECTS AND METHODS: A cohort of 366 men with no established diagnosis of prostate cancer completed a questionnaire addressing SUI, ED and associated bother. Socio-economic status and presence of comorbidities were also examined. RESULTS: The mean (range) age of the men was 54.8 (33-80) years; 90% of the men (271) had no SUI, and 76% (231) reported no urinary bother. Conversely, 62% (189) reported some degree of ED and 27% (82) some degree of sexual bother. Urinary bother (P < 0.001), erectile function (P < 0.001), and sexual bother (P < 0.02) were associated with age. Of all the men, 36% had one or more comorbidities. Men with one or more comorbidities had worse erectile function than those men with no comorbidity (P < 0.05). CONCLUSION: Few studies address normative values of SUI and ED rates in men with no established diagnosis of prostate cancer. We quantified the rate of SUI and it was practically negligible. Conversely, some degree of ED affected most of the present screened population. These data may be used as baseline references to evaluate the magnitude of functional and bother detriments after various prostate treatments.

High radical prostatectomy surgical volume is related to lower radical prostatectomy total hospital charges.

OBJECTIVE: To test the hypothesis that individual surgical volume (SV) is an independent predictor of radical prostatectomy (RP) total charges. METHODS: We used the Florida State Inpatient Data File. ICD-9 codes 60.5 (RP) and 185 (prostate cancer) identified all men treated with RP for prostate cancer between January 1 and December 31, 1998. Among 1,923,085 records, 3167 RPs were selected. SV represented the predictor. Total RP charges represented the outcome. Age, race, and comorbidity represented covariates. Univariate and multivariate linear regression models were used. RESULTS: All 3167 RPs were performed by 81 surgeons. SV ranged from 2 to 162 (mean, 68). Charges were 4755 dollars to 140,201 dollars (mean, 18,200 dollars). In the multivariate model, each SV increment corresponding to one RP reduced hospital charges by 25 dollars (p < or = 0.001). CONCLUSIONS: Redistribution of RPs from low to high SV users could result in significant savings. For example, 4 million dollars could be saved if 1000 RPs were redistributed from surgeons with an SV of 18 to surgeons with an SV of 200.

Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder.

OBJECTIVE: To assess the contemporary inter-institutional accuracy of urinary cytology in predicting the recurrence of transitional cell carcinoma (TCC) of the bladder, in a large multi-institutional cohort from four continents, as cystoscopy and urinary cytology represent the 'gold standards' for surveillance of TCC recurrences, but the ability of cytology to predict recurrence varies. PATIENTS AND METHODS: Ten institutions contributed 2542 patients with a history of superficial TCC, of whom 898 had TCC recurrence. Age- and gender-adjusted logistic regression models were used to evaluate the association between urine cytology and TCC recurrence. The predictive accuracy derived from the logistic regression model was tested using the area under the receiver operating characteristic curve. The resulting predictive accuracy estimates were internally validated with 200 bootstrap re-samples. RESULTS: The mean (range across institutions) age of the patients was 65 (48-69) years and 75 (67-87)% were men. Cytology was positive in 19 (10-38)% of patients; recurrence was identified in 35 (27-54)% of patients. The sensitivity was 38-65% across institutions. Urinary cytology varied significantly in its ability to predict recurrence of bladder cancer. Institution-specific predictive accuracy adjusted for gender and age was 0.627-0.893. Stratifying by grade and stage only partly attenuated the discrepancies between centres. CONCLUSIONS: The variability of urinary cytology results was very appreciable among the 10 centres and ranged from poor (63%) to excellent (89%).

Development and validation of a nomogram predicting the outcome of prostate biopsy based on patient age, digital rectal examination and serum prostate specific antigen.

PURPOSE: We developed and validated a nomogram which predicts presence of prostate cancer (PCa) on needle biopsy. MATERIALS AND METHODS: We used 3 cohorts of men who were evaluated with sextant biopsy of the prostate and whose presenting prostate specific antigen (PSA) was not greater than 50 ng/ml. Data from 4,193 men from Montreal, Canada were used to develop a nomogram based on age, digital rectal examination (DRE) and serum PSA. External validation was performed on 1,762 men from Hamburg, Germany. Data from these men were subsequently used to develop a second nomogram in which percent free PSA (%fPSA) was added as a predictor. External validation was performed using 514 men from Montreal. Both nomograms were based on multivariate logistic regression models. Predictive accuracy was evaluated with areas under the receiver operating characteristic curve and graphically with loess smoothing plots. RESULTS: PCa was detected in 1,477 (35.2%) men from Montreal, 739 (41.9%) men from Hamburg and 189 (36.8%) men from Montreal. In all models all predictors were significant at 0.05. Using age, DRE and PSA external validation AUC was 0.69. Using age, DRE, PSA and %fPSA external validation AUC was 0.77. CONCLUSIONS: A nomogram based on age, DRE, PSA and %fPSA can highly accurately predict the outcome of prostate biopsy in men at risk for PCa.

Validation of 1997 Partin Tables' lymph node invasion predictions in men treated with radical prostatectomy in Montreal Quebec.

OBJECTIVE: The accuracy of 1997 Partin Tables' lymph node invasion (LNI) predictions exhibits important variability in different testing populations. We explored the LNI predictive accuracy in radical prostatectomy (RP) patients from Montreal, Canada. Moreover, we assessed the extent of change in predictive accuracy related to a modification of PSA coding from categorical to continuous. METHODS: We used pretreatment serum PSA, clinical stage, and biopsy Gleason sum from 537 men treated with RP to compare predicted and observed rates of LNI. Accuracy was quantified with receiver-operating characteristics curves. RESULTS: Accuracy was 0.760 in 369 evaluable patients, when categorically coded pretreatment PSA (0-4, 4.1-10, 10.1-20, 20.1+) was combined with clinical stage and biopsy Gleason sum. A 2.7% accuracy increase was noted when categorically coded PSA was replaced with continuously coded values. CONCLUSION: Partin Tables' LNI predictions showed comparable accuracy to a community-based sample from the United States (0.766), and to a recent, multi-institutional sample (0.740). However, accuracy was lower than reported in internal (0.818), and external (0.837) academic, validation cohorts. Accuracy of LNI predictions was appreciably higher, when continuously coded PSA was used.