Impact of prostate-specific antigen on a baseline prostate cancer risk assessment including genetic risk.

OBJECTIVE: To determine to what extent prostate cancer (PCa) risk prediction is improved by adding prostate-specific antigen (PSA) to a baseline model including genetic risk. METHODS: Peripheral blood deoxyribonucleic acid was obtained from Caucasian men undergoing prostate biopsy at the University of Toronto (September 1, 2008 to January 31, 2010). Thirty-three PCa risk-associated single nucleotide polymorphisms were genotyped to generate the prostate cancer genetic score 33 (PGS-33). Primary outcome is PCa on study prostate biopsy. Logistic regression, area under the receiver-operating characteristic curves (AUC), and net reclassification improvement were used to compare models. RESULTS: Among 670 patients, 323 (48.2%) were diagnosed with PCa. The PGS-33 was highly associated with biopsy-detectable PCa (odds ratio, 1.66; P = 5.86E-05; AUC, 0.59) compared with PSA (odds ratio, 1.33; P = .01; AUC, 0.55). PSA did not improve risk prediction when added to a baseline model (age, family history, digital rectal examination, and PGS-33) for overall risk (AUC, 0.66 vs 0.66; P = .86) or Gleason score ≥7 PCa (AUC, 0.71 vs 0.73; P = .15). Net reclassification improvement analyses demonstrated no appropriate reclassifications with the addition of PSA to the baseline model for overall PCa but did show some benefit for reclassification of men thought to be at higher baseline risk in the high-grade PCa analysis. CONCLUSION: In a baseline model of PCa risk including the PGS-33, PSA does not add to risk prediction for overall PCa for men presenting for "for-cause" biopsy. These findings suggest that PSA screening may be minimized in men at low baseline risk.

The impact of the use of aspirin and other nonsteroidal anti-inflammatory drugs on the risk of prostate cancer detection on biopsy.

OBJECTIVE: To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of prostate cancer (PC) detection in men undergoing biopsy. METHODS: Men were identified using our academic institution's prospectively maintained prostate biopsy database. Patients were classified as aspirin (ASA) users, users of other NSAIDs, or nonusers. The primary outcome was any PC on biopsy, and the secondary outcome was clinically significant PC (CSPC; Gleason sum ≥7). Multivariate logistic regression analyses were performed to adjust for a priori defined clinical confounders. RESULTS: Of 839 patients, 408 (48.6%) were diagnosed with PC and 201 (24.0%) had CSPC. A higher proportion of ASA users (63.5%) and other NSAID users (61.2%) had PC compared with nonusers (41.9%; P <.001). CSPC was more common among ASA users (34.9%; P <.001) compared with other NSAID users (20.0%) and nonusers (20.9%). In multivariate regression analyses, ASA use (odds ratio [OR] = 2.04; 95% confidence interval [CI] = 1.32-3.13; P = .001) and other NSAID use (OR = 2.42; 95% CI = 1.36-431; P = .003) were associated with higher odds of PC detection, whereas ASA use was associated with higher odds of CSPC (OR = 1.62; 95% CI = 1.00-2.62; P = .048). CONCLUSION: In men undergoing biopsy, ASA and other NSAID use were associated with increased probability of detecting PC, whereas ASA use was associated with the risk of detecting CSPC. Although NSAID use might have a protective biological effect against PC, men who develop elevated prostate-specific antigen levels while on NSAIDs may nonetheless be less likely to have an inflammatory etiology and more likely to harbor PC. It may be warranted for clinicians to consider the influence of NSAIDs when evaluating patients being considered for biopsy.

Regular transition zone biopsy during active surveillance for prostate cancer may improve detection of pathological progression.

PURPOSE: We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance. MATERIALS AND METHODS: Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression. RESULTS: A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02). CONCLUSIONS: Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk.

A negative confirmatory biopsy among men on active surveillance for prostate cancer does not protect them from histologic grade progression.

BACKGROUND: Many men (21-52%) are reported to have no cancer on the second, also known as the confirmatory, biopsy (B2) for prostate cancer active surveillance (AS). If these men had a reduced risk of pathologic progression, particularly grade related, the intensity of their follow-up could be decreased. OBJECTIVE: To investigate if men with no cancer on B2 are less likely to undergo subsequent pathologic progression. DESIGN, SETTING, AND PARTICIPANTS: Men were identified from our tertiary care center AS prostate cancer database (1995-2012). Eligibility criteria were prostate-specific antigen (PSA) ≤ 10, cT2 or lower, no Gleason grade 4 or 5, three or fewer positive cores, and no core >50% involved. Only patients with three or more biopsies were selected and then dichotomized on cancer status (yes or no) at B2. INTERVENTION AS OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pathologic progression was defined as grade (advancement in Gleason score) and/or volume (more than three positive cores, >50% core involved). Progression-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model. RESULTS AND LIMITATIONS: Of the 286 patients remaining on AS after B2, 149 (52%) had no cancer and 137 (48%) had cancer. The median follow-up after B2 was 41 mo (interquartile range [IQR]: 26.5-61.9). Progression-free survival at 5 yr was 85.2% versus 67.3% for negative B2 versus cancer on B2, respectively (p = 0.002). Men with no cancer at B2 had a 53% reduction in risk of subsequent progression (hazard ratio [HR]: 0.47; 95% confidence interval [CI], 0.29-0.77; p = 0.003). Subanalysis showed prognostic indicators of volume-related progression were absence of cancer (HR: 0.36; 95% CI, 0.20-0.62; p = 0.0006) and PSA density (HR: 1.79; 95% CI, 1.12-2.89; p = 0.01). The only predictor of grade-related progression was age (HR: 1.05; 95% CI, 1.00-1.10; p = 0.04). Retrospective analysis was the major limitation of the study. CONCLUSIONS: Absence of cancer on B2 is associated with a significantly decreased risk of volume-related but not grade-related progression. This must be considered when counseling men on AS.

Obesity is associated with larger prostate volume but not with worse urinary symptoms: analysis of a large multiethnic cohort.

OBJECTIVE: To evaluate the associations between body mass index (BMI) and prostate volume (PV) and lower urinary tract symptoms in a multiethnic cohort. METHODS: A cohort of men without prostate cancer seen at our institution was assembled, excluding those with previous transurethral resection of the prostate. Height and weight were measured to compute BMI, PV was measured by transrectal ultrasound, and the International Prostate Symptom Score (IPSS) questionnaire was administered. After stratified bivariate analyses, multiple linear regression and ordinal logistic regression models were used to assess the independent effect of BMI on PV and IPSS, respectively. RESULTS: The cohort included 1613 patients, and mean BMI was 27.1 kg/m(2). Patients with a BMI of <25.0, 25.0-29.9, and 30.0-34.9 had a median PV of 44.0 mL, 48.0 mL, and 52.0 mL, respectively. The African ethnicity subgroup generally had larger median PVs than European and Asian subgroups and had the largest differences in median PV between normal and obese men. There were no significant differences in IPSS or usage of benign prostatic hyperplasia medications between BMI categories. In multivariable analyses, higher BMI was associated with larger PV (P <.001) but not IPSS (P = .91). On the basis of our model, given a PV of 40 mL, 50 mL, and 60 mL, each 5 kg/m(2) increase in BMI was associated with a 2.19 mL, 2.74 mL, and 3.29 mL increase in PV, respectively. Body weight (P <.001) but not height (P = .13) was associated with PV. CONCLUSION: Higher BMI is associated with larger PV but not worse lower urinary tract symptoms (measured using IPSS). Usage rate of alpha blockers or 5 alpha reductase inhibitors was not significantly different between BMI categories.

PTEN losses exhibit heterogeneity in multifocal prostatic adenocarcinoma and are associated with higher Gleason grade.

Prostatic adenocarcinoma is an epithelial malignancy characterized by marked histological heterogeneity. It most often has a multifocal distribution within the gland, and different Gleason grades may be present within different foci. Data from our group and others have shown that the genomic deletion of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene and the disruption of the ETS gene family have a central role in prostate cancer and are likely to be associated with Gleason grade. In this study, prostate cancer samples were systematically analyzed to determine whether there was concordance between PTEN losses and TMPRSS2-ERG fusion rearrangements, within or between foci in multifocal disease, using well-annotated tissue microarrays (TMAs) consisting of 724 cores derived from 142 radical prostatectomy specimens. Three-color fluorescence in situ hybridization analysis of both the PTEN deletion and the TMPRSS2-ERG fusion was used to precisely map genetic heterogeneity, both within and between tumor foci represented on the TMA. PTEN deletion was observed in 56 of 134 (42%) patients (hemizygous=42 and homozygous=14). TMPRSS2-ERG fusion was observed in 63 of 139 (45%) patients. When analyzed by Gleason pattern for a given TMA core, PTEN deletions were significantly associated with Gleason grades 4 or 5 over grade 3 (P<0.001). Although TMPRSS2-ERG fusions showed a strong relationship with PTEN deletions (P=0.007), TMPRSS2-ERG fusions did not show correlation with Gleason grade. The pattern of genetic heterogeneity of PTEN deletion was more diverse than that observed for TMPRSS2-ERG fusions in multifocal disease. However, the marked interfocal discordance for both TMPRSS2-ERG fusions and PTEN deletions was consistent with the concept that multiple foci of prostate cancer arise independently within the same prostate, and that individual tumor foci can have distinct patterns of genetic rearrangements.

Active surveillance failure for prostate cancer: does the delay in treatment increase the risk of urinary incontinence?

INTRODUCTION: Active surveillance for low risk prostate cancer has become an acceptable management strategy. However, a percentage of these patients in active surveillance move on to active treatment. Our aim was to examine urinary incontinence (UI) rates in men who move on to treatment from active surveillance and compare it to quoted rates in the literature. We examined the question that a potential delay in the treatment of prostate cancer in those on active surveillance may result in an increase in incontinence rates. MATERIALS AND METHODS: From July 1992 to June 2009, 443 men at our institution entered into active surveillance for newly diagnosed prostate cancer. We reviewed their medical records and data was abstracted from physician-reported medical records. The mean age of the entire group was 64.1 years old (range 40-80). Their mean prostate-specific antigen (PSA) was 7.65 (range 0.21-36) and their mean Gleason score was 6.2 (range 4-8). Of these patients on active surveillance, 150/443 (33.3%) went on to active treatment. Median time to active treatment was 31.5 months (range 3-180 months). Only 5 patients went onto active treatment less than 1 year after starting active surveillance. Of these patients who went onto active treatment, 85 had radiation alone, 48 had a radical prostatectomy (RP), 7 had a RP and radiation, 7 had HIFU alone, 2 had focal ablation and 1 had HIFU followed by salvage RP. Of those undergoing radiation (92 patients), 66 had external beam and 26 had brachytherapy. RESULTS: Prior to active treatment 25/443 (5.6%) patients had UI documented in their history. Of those 25 patients only 3 went on to a RP and all had persistent UI after surgery. Two of the 25 patients went on to radiation therapy and their UI resolved. In the active treatment groups, after RP alone, 14/48 (29.2%) patients had new onset UI that persisted at a mean of 47.2 months (range 11-149 months) postoperatively. Of these 14 patients, 7 patients (14.6%) had significant leakage (> 1 pad/day). After radiation therapy alone 2/85(2.4%) had new onset persistent UI at 34 and 49 months post radiation. Only 1/7 (14.3%) patients that had high intensity focused ultrasound (HIFU) alone had persistent UI at 38 months after HIFU. Of the 7 patients that had both a RP and radiation, 2 had persistent significant UI at 49 and 153 months after surgery. One patient that had HIFU and a RP had persistent UI at 23 months post surgery. The 2 patients that had focal ablation were dry. CONCLUSIONS: The UI rates in our cohort of active surveillance patients who move on to active treatment are similar to patients who undergo treatment immediately after prostate cancer is diagnosed as quoted in the literature. This suggests that active surveillance, as an initial mode of therapy, does not increase the risk of UI if active treatment occurs at a later date.

Effects of partial nephrectomy on postoperative blood pressure.

PURPOSE: The effects of partial nephrectomy (PN) on postoperative blood pressure (BP) are not known, and PN has the potential to worsen BP. We therefore sought to determine whether PN alters postoperative BP. MATERIALS AND METHODS: Patients who underwent PN for suspected malignancy at our institution from 2002 to 2008 were included. Data on BP and medication from before and after PN were retrieved from family physicians. BP and number of antihypertensive medications were compared after surgery with preoperative values by use of paired t tests and Chi-squared analyses, respectively. RESULTS: Of 74 patients undergoing PN and providing consent, 48 met the inclusion and exclusion criteria, with a median follow-up of 24 months. For the early postoperative period (1 month to 1 year after surgery), the mean BPs (132.3/77.0 mmHg) were unchanged compared with preoperative values (132.4/78.0 mmHg; p=0.59 systolic BP and p=0.30 diastolic BP). For the later postoperative period (beyond 1 year after surgery), the mean postoperative systolic BP was unchanged from the mean preoperative systolic BP (131.2 mmHg vs. 132.4 mmHg, respectively; p>0.30). However, the corresponding average diastolic BP was lower in the long term (78.0 mmHg versus 76.4 mmHg respectively; p=0.01). No significant difference in the mean number of BP medications prescribed preoperatively, at one year, and beyond one year was identified (p>0.37). CONCLUSIONS: PN does not result in initial or long-term postoperative deterioration in BP.

Measurement of peri-prostatic fat thickness using transrectal ultrasonography (TRUS): a new risk factor for prostate cancer.

UNLABELLED: Study Type - Prognosis (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? ADIPOSE tissue secretes various endocrine and paracrine mediators. Some authors have begun to consider whether peri-prostatic fat (PPF) may interact with the prostate and play a role in carcinogenesis. It has recently been shown that the PPF quantity measured by CT is associated with more aggressive disease in patients undergoing radiation therapy. Our group studied a population not yet diagnosed with prostate cancer. By doing so we were able to identify PPF thickness on transrectal ultrasonography as a risk factor for prostate cancer detection upon biopsy, and as a risk factor for high-grade disease. Our study also raises interesting questions about the underlying mechanisms of the association between PPF quantity and prostate cancer. OBJECTIVE: To determine if the amount of peri-prostatic fat (PPF) on transrectal ultrasonography (TRUS) is a risk factor for incident prostate cancer overall and high-grade prostate cancer (Gleason ≥4). PATIENTS AND METHODS: A prospectively maintained database of patients undergoing prostate biopsy at Princess Margaret Hospital for cancer suspicion was used. • All TRUS examinations were retrospectively reviewed upon 'blinding' to outcome. • PPF thickness, measured as the distance between the prostate and the pubic bone, was used as an index of the quantity of PPF. • PPF measurements, together with other prostate cancer risk factors, were evaluated against prostate cancer and high-grade prostate cancer detection upon biopsy with univariable and multivariable logistic regression and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: Of the 931 patients, 434 (47%) were diagnosed with prostate cancer and 218 (23%) were diagnosed with high-grade prostate cancer. • The mean (range) PPF thickness was 5.3 (0-15) mm. • Increasing PPF thickness was associated with prostate cancer and high-grade prostate cancer diagnosis, with graded effect. When adjusting for other variables, the odds of detecting any prostate cancer and high-grade prostate cancer increased 12% (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.23) and 20% (OR 1.20, 95% CI 1.07-1.34), respectively, for each millimetre increase in PPF thickness. • The AUCs for the association of PPF with prostate cancer and high-grade prostate cancer were 0.58 (95% CI 0.54-0.62) and 0.59 (95% CI 0.55-0.64), respectively. CONCLUSION: The amount of PPF can be estimated with TRUS and is a predictor of prostate cancer and high-grade prostate cancer at biopsy. To our knowledge, this study is the first to investigate PPF quantity in patients without prior prostate cancer diagnosis.

Sex differences in bladder cancer outcomes among smokers with advanced bladder cancer.

OBJECTIVE: To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population. PATIENTS AND METHODS: A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied. In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed. Categorical data were analyzed by the chi-squared test and numerical data were analyzed by Student's t-test. The Kaplan-Meier method, log-rank test and a proportional hazards model were used to estimate the effect of smoking on survival. RESULTS: In total, 352 patients (64%) were smokers and 194 (36%) were non-smokers. Smokers had more frequently advanced tumours and nodal metastasis. The 10-year disease-specific survival (DSS) was 52% vs 66% for smokers and non-smokers, respectively (P = 0.039). Smokers also had significantly worse overall survival (10-year overall survival 37% vs 62%; P = 0.015). Smoking affected significant DSS among men (P = 0.012), although no effect was observed among women. In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0-1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1-1.8) for overall mortality. In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8-1.6; P = 0.41). In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1-2.3; P = 0.007). CONCLUSIONS: Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival. Smoking affected survival only among men. Women had poorer survival but smoking was not a contributing factor to this.

Alterations in urinary metabolites due to unilateral ureteral obstruction in a rodent model.

Urinary tract obstruction (UTO) results in renal compensatory mechanisms and may progress to irrecoverable functional loss and histologic alterations. The pathophysiology of this progression is poorly understood. We identified urinary metabolite alterations in a rodent model of partial and complete UTO using (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy. Principal component analysis (PCA) was used for classification and discovery of differentiating metabolites. UTO was associated with elevated urinary levels of alanine, succinate, dimethylglycine (DMG), creatinine, taurine, choline-like compounds, hippurate, and lactate. Decreased urinary levels of 2-oxoglutarate and citrate were noted. The patterns of alteration in partial and complete UTO were similar except that an absence of elevated urinary osmolytes (DMG and hippurate) was noted in complete UTO. This pattern of metabolite alteration indicates impaired oxidative metabolism of the mitochondria in renal proximal tubules and production of renal protective osmolytes by the medulla. Decreased production of osmolytes in complete obstruction better elucidates the pathophysiology of progression from renal compensatory mechanisms to irrecoverable changes. Further confirmation of these potential biomarkers in children with UTO is necessary.

Comparison of risk calculators from the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer in a contemporary Canadian cohort.

OBJECTIVE: •To compare the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC-RC) in a single-institution Canadian cohort. PATIENTS AND METHODS: •At Princess Margaret Hospital, 982 consecutive patients with PCPT-RC and ERSPC-RC covariables were prospectively catalogued before prostate biopsy for suspicion of prostate cancer (PCa). •Receiver-operating characteristic (ROC) curves were generated for each calculator and prostate-specific antigen (PSA). •Comparisons by area under the curve (AUC) and calibration plots were performed. •Predictors of PCa were identified by univariable and multivariable logistic regression. RESULTS: •PCa was detected in 46% and high-grade (HG) PCa (Gleason ≥4) in 23% of subjects with a median PSA level of 6.02 ng/mL. • Multivariable analysis identified transrectal ultrasonography nodule, prostate volume and PSA as the most important predictors of PCa and HG PCa. •ROC curve analysis showed that the ERSPC-RC (AUC = 0.71) outperformed the PCPT-RC (AUC = 0.63) and PSA (AUC = 0.55), for PCa prediction, P < 0.001. •The PCPT-RC was better calibrated in the higher prediction range (40-100%) than the ERSPC-RC, whereas the ERSPC-RC had better calibration and avoided more biopsies in the lower risk range (0-30%). •Discrimination of the ERSPC-RC continued to be superior to the PCPT-RC when the cohort was stratified by different clinical variables. CONCLUSIONS: •The ERSPC-RC had better discrimination for predicting PCa compared to the PCPT-RC in this Canadian cohort. •Calibration would need to be improved to allow routine use of the ERSPC-RC in Canadian practice.

An analysis of world media reporting of two recent large randomized prospective trials investigating screening for prostate cancer.

OBJECTIVES: •The publication of two large screening studies for prostate cancer (CaP), the Prostate Lung Colorectal Ovarian Cancer (PLCO) and the European Randomized Study of Screening for Prostate Cancer (ERSPC), has generated intense interest in medical and lay press not only as a result of their robust size, but also their opposing outcomes and differing methodologies, making interpretation controversial. •To characterize the world online media response to the studies by assessing reports for quality and message, as well as noting geographical differences. MATERIALS AND METHODS: •Major newspapers in North America, UK and Australia reporting online and Internet-only news organizations were analyzed for their reporting of CaP screening in response to the trials for a period of 6 months post-release. •Content, positive or negative projection regarding screening, and use of expert commentary were recorded. •Statistical analysis of the results was then undertaken. RESULTS: •In total, 48 newspapers reported the CaP screening studies with a median (range) publication time for newsprint online of 1.5 (0-175) days and same day appearance for online news sources in the range 0-110 days. •Only 23% of newsprint articles indicated that screening was a positive endeavour, whereas 31% were negative and the remainder were neutral (46%). •Some 78% of UK articles indicated insufficient screening, whereas 57% in the USA and 80% in Canada reported screening as being excessive. Online media reflected USA reporting. CONCLUSIONS: •World newsprint media in general portrayed screening in a negative light after publication of the ERSPC and PLCO studies. •North American media concluded that prostate-specific antigen (PSA) screening was excessive, whereas the UK media indicated that an inadequate level of PSA screening is occurring. •The media influences public opinion and government policy and it is important that urological organizations are aware of the true impact.

Growth kinetics of renal masses: analysis of a prospective cohort of patients undergoing active surveillance.

BACKGROUND: Active surveillance (AS) represents a treatment option for renal masses in patients who are not surgical candidates either because of existing comorbidities or patient choice. Among renal masses undergoing AS, some grow rapidly and require treatment or progress to metastatic disease. Patient and tumour characteristics related to this more aggressive behaviour have been poorly studied. OBJECTIVE: To report the analysis of a multi-institutional cohort of patients undergoing AS for small renal masses. DESIGN, SETTING, AND PARTICIPANTS: This prospective study included 82 patients with 84 renal masses who underwent AS in three Canadian institutions between July 2001 and June 2009. INTERVENTION: All patients underwent AS for renal masses presumed to be renal cell carcinoma (RCC) as based on diagnostic imaging. MEASUREMENTS: Age, sex, symptoms at presentation, maximum diameter at diagnosis (cm), tumour location (central/peripheral), degree of endophytic component (1-100%), and tumour consistency (solid/cystic) were used to develop a predictive model of the tumour growth rate using binary recursive partitioning analysis with a repeated measures outcome. RESULTS AND LIMITATIONS: With a median follow-up of 36 mo (range: 6-96), the mean annual renal mass growth rate for the entire cohort was 0.25 cm/yr (standard deviation [SD]: 0.49 cm/yr). Only one patient (1.2%) developed metastatic RCC. Amongst all variables, maximum diameter at diagnosis was the only predictor of tumour growth rate, and two distinct growth rates were identified. Masses that are ≥2.45 cm in largest diameter at diagnosis grow faster than smaller masses. This series was limited by its moderate sample size, although it is the largest published prospective series to date. CONCLUSIONS: We confirm that most renal masses grow slowly and carry a low metastatic potential. Tumour size is a predictor of tumour growth rate, with renal masses <2.45 cm growing more slowly than masses >2.45 cm.

Long-term follow-up of T1 high-grade bladder cancer after intravesical bacille Calmette-Guérin treatment.

OBJECTIVE: To report the long-term results of bacille Calmette-Guérin (BCG) intravesical therapy in relation to disease progression and recurrence in primary T1 high-grade (HG) bladder cancer (BC) confirmed by central pathological review. PATIENTS AND METHODS: In all, 136 patients from two university centres (Rotterdam, n = 49; Toronto, n = 87) were diagnosed with primary T1HG BC. One experienced uro-pathologist reviewed all slides, ensuring all cases were indeed HG and that muscle was present in all specimens. Patients were treated with BCG induction (six instillations) after transurethral resection (TUR) of the tumour and followed with cystoscopy and urinary cytology. Predictors for recurrence, progression and survival were assessed with multivariable Cox regression models. RESULTS: Mean (range) follow-up was 6.5 (0.3-21.6) years. There were no significant differences for recurrence (P = 0.52), progression (P = 0.35) and disease-specific survival (DSS) (P = 0.69) between the two centres. Among the cohort, 47 patients (35%) recurred and 42 (30.9%) progressed with a median time to progression of 2.1 years; 16 (38%) of these progressions occurred ≥ 3 years after the initial BCG course; 22 (16%) patients who progressed died from BC. Overall, 96 (71%) patients had no evidence of disease at the last follow-up. Carcinoma in situ was the only independent predictor for recurrence in multivariate analysis (P = 0.011). No independent predictors were found for progression. CONCLUSIONS: Conservative treatment with BCG is a valid option in primary T1HG BC. Nevertheless, the aggressive nature of T1HG BC is evident in the fact that 30% progressed, with a high proportion of these progression events occurring ≥ 3 years after BCG. Caution should be exercised when relying on the long-term effects of BCG, and close follow-up of these patients should not be neglected.

Impact of 5α-reductase inhibitors on men followed by active surveillance for prostate cancer.

BACKGROUND: In two large randomized controlled trials, 5α-reductase inhibitors (5-ARIs) were shown to prevent prostate cancer. No prior work had shown the effect of 5-ARIs on those already diagnosed with low-risk prostate cancer. OBJECTIVE: Our aim was to determine the effect of 5-ARIs on pathologic progression in men on active surveillance. DESIGN, SETTING, AND PARTICIPANTS: We conducted a single-institution retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on active surveillance for prostate cancer. MEASUREMENTS: Pathologic progression was evaluated and defined as Gleason score >6, maximum core involvement >50%, or more than three cores positive on a follow-up prostate biopsy. Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression. RESULTS AND LIMITATIONS: A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 mo (interquartile range: 23.6-59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5-ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%; p=0.004) and were less likely to abandon active surveillance (20% vs 37.6%; p=0.006). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (hazard ratio: 2.91; 95% confidence interval, 1.5-5.6). The main study limitation was the retrospective design and variable duration of 5-ARI therapy. CONCLUSIONS: The 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance.

Prevention strategies in prostate cancer.

Prostate cancer (PCa) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (PCPT) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are important factors to consider.This review provides a comparative update on the REDUCE and PCPT trials and some clinical recommendations. Other potential primary preventive strategies with statins, selective estrogen response modulators, and nutraceutical compounds-including current evidence for these agents and their roles in clinical practice-are discussed. Many substances that have been examined in the primary prevention of pca and for which clinical data are either negative or particularly weak are not covered.The future of PCa prevention continues to expand, with several ongoing clinical trials and much interest in tertiary prostate cancer prevention.

Nutraceuticals and prostate cancer prevention: a current review.

Nutraceuticals are 'natural' substances isolated or purified from food substances and used in a medicinal fashion. Several naturally derived food substances have been studied in prostate cancer in an attempt to identify natural preventative therapies for this disease. Vitamin E, selenium, vitamin D, green tea, soy, and lycopene have all been examined in human studies. Other potential nutraceuticals that lack human data, most notably pomegranate, might also have a preventative role in this disease. Unfortunately, most of the literature involving nutraceuticals in prostate cancer is epidemiological and retrospective. The paucity of randomized control trial evidence for the majority of these substances creates difficulty in making clinical recommendations particularly when most of the compounds have no evidence of toxicity and occur naturally. Despite these shortcomings, this area of prostate cancer prevention is still under intense investigation. We believe many of these 'natural' compounds have therapeutic potential and anticipate future studies will consist of well-designed clinical trials assessing combinations of compounds concurrently.