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Introduction: Several androgen deprivation therapy (ADT) medications are available for treating advanced prostate cancer with roughly equivalent oncological efficacy and tolerability. We investigated the proportion of physicians who predominantly prescribe one type of ADT drug (“mono-prescriber”) and assessed characteristics associated with prescription behavior. Methods: Ontario men aged ≥65 years who were diagnosed with advanced prostate cancer (1997–2017) and initiated ADT thereafter for ≥3 consecutive months were identified using population-level administrative data. Their first prescription for injectable ADT was linked to a physician, and urologists with ≥10 prescriptions over the study period were included in the analysis (n=282). Urologists were classified as high mono-prescribers if ≥80% of their prescriptions were for one drug type. Multivariable logistic regression was used to examine the association of physician characteristics with the odds of being a high mono-prescriber. Results: Overall, 67 (23.8%) of urologists were classified as high mono-prescribers but the frequency varied across health planning regions. The most commonly prescribed drugs and those used by mono-prescribers were goserelin (41.8% and 56.7%) and leuprolide (44.3% and 43.3%), respectively. In multivariable analysis, the odds of a physician being a high mono-prescriber were higher with more years in practice (odds ratio [OR] 1.06/ year, 95% confidence interval [CI] 1.03–1.09, p

Pathological and oncologic outcomes of delayed radical prostatectomy following prostate cancer active surveillance are not well established. We determined the pathological and oncologic outcomes of favorable risk, Grade Group 1, prostate cancer managed with active surveillance and progressing to radical prostatectomy for clinically significant prostate cancer (Grade Group 2 or greater).Between 1992 and 2015, 170 men with favorable risk prostate cancer underwent delayed radical prostatectomy for clinically significant prostate cancer (ASRP) at the Princess Margaret Cancer Centre. Pathological and oncologic outcomes of the ASRP cohort were compared with a matched cohort treated with up-front radical prostatectomy (405) immediately before surgery. Biochemical recurrence-free survival, overall survival and cancer specific survival were compared. We examined the association between delayed radical prostatectomy and adverse pathology at radical prostatectomy and biochemical recurrence using logistic and Cox regression analyses, respectively.Median time spent on active surveillance before radical prostatectomy was 31.0 months. At radical prostatectomy pT3 (extraprostatic extension, seminal vesicle invasion), positive surgical margin and pN1 rates were comparable between the 2 cohorts. Median followup after radical prostatectomy was 5.6 years. The 5-year biochemical recurrence-free survival rate in the ASRP cohort and up-front radical prostatectomy cohort were 85.8% and 82.4%, respectively (p=0.38). Overall survival and cancer specific survival were comparable between the 2 groups. Delayed radical prostatectomy was not associated with adverse pathological outcomes and biochemical recurrence on regression analyses.Curative intent radical prostatectomy after a period of active surveillance results in excellent pathological and oncologic outcomes at 5 years. A period of active surveillance does not result in inferior outcomes compared to patients with similar risk characteristics undergoing up-front radical prostatectomy.

BACKGROUND Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS. MATERIALS/SUBJECTS AND METHODS The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995-2016). Pathologic, grade, and volume progression were the primary end points. Kaplan-Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time. RESULTS The cohort included 288 men with median follow-up of 82 months (interquartile range: 37-120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p

Introduction: Active surveillance (AS) of small renal masses (SRM) is increasingly recognized as a safe option. A recent U.S. study found that half of patients receiving treatment on AS were for preference, but these findings may not be generalizable to other jurisdictions and healthcare models. We aimed to investigate AS failure rates and causes among a contemporary biopsy-evaluated cohort in Canada. Methods: A retrospective review was performed of SRM patients on AS undergoing treatment at our tertiary care center (1999–2018). All patients had undergone renal biopsy and been diagnosed with renal cell carcinoma (RCC). Demographic and clinical parameters surrounding the decision to treat were extracted from chart review. Indications for treatment were dichotomized into clinical (radiographical) progression or preference. Qualitative assessment of clinic notes confirmed treatment indication. Ethics approval was obtained. Results: A total of 38 SRM-RCC patients who underwent treatment on AS were identified, of which 29 had been on AS ≥1 year. Most (75.9%) were male, and the mean age beginning AS was 65.9±9.0 years. Most patients had clear-cell RCC with low-grade disease. Seventeen of 29 (58.6%) patients experienced clinical progression after 3.82 (2.57–7.16) years, whereas preference accounted for 12/29 (41.4%) after 2.22 (1.69–3.53) years (time-to-treatment p=0.032). The longest duration on AS was 14.2 years prior to clinical progression. No patients had metastatic progression before treatment. Conclusions: Two-fifths of patients received treatment for preference and at a much higher rate vs. clinical progression. These findings suggest a clinical gap where effective patient counselling, prior to and during AS, may improve adherence.

Summary Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC., Genetic factors may distinguish who should receive active surveillance (AS) versus treatment following prostate cancer diagnosis. We undertook the first study to investigate this and report novel variants, genes, and risk scores associated with AS outcomes. These findings could help inform and individualize the decision of AS.

Phase-III randomized control trial evidence suggests intermittent androgen deprivation therapy (IADT) is not significantly inferior to continuous androgen deprivation therapy (ADT) for patients with prostate cancer (PC). However, clinical practice and guidelines differ in their recommendations. We evaluate real-world utilization and practice patterns of IADT.Ontario men ≥65 years of age with PC who initiated ADT for ≥3 months were identified (1997-2017). Lapses in ADT ≥6 months (initial gap) and ≥3 months (subsequent gaps) were used to classify IADT. Neoadjuvant/adjuvant therapy was excluded. Disease stage adjustment was completed for patients with likely metastatic disease based on de novo presentation with ADT. Patient and physician predictors of IADT were analyzed using multivariable logistic regression.We identified 8,544 patients with 1,715 having previously received local therapy. Among all patients, 16.4% received IADT. This ranged from 11.4%-24.8% across health-planning regions and increased to 26.6% in those with previous local therapy. Mean followup was 8.3 years. Patients with prior local therapy (OR 1.85, 95% CI 1.59-2.17, p0.001) and those in the highest income quintile (OR 1.32, 95% CI 1.08-1.60, p=0.005) had increased odds of receiving IADT. Radiation oncologists were more likely to use IADT than urologists (OR 1.99, 95% CI 1.59-2.50, p0.001), as were physicians with more experience (≥10 years in practice: OR 1.44, 95% CI 1.11-1.88, p=0.007). In specialty-stratified analyses, case volume was significantly associated with IADT for radiation oncologists (highest quartile: OR 1.73, 95% CI 1.14-2.62, p=0.009).IADT remains underutilized for patients with PC who ≥65 years of age with only 1 in 4 to 1 in 6 eligible patients receiving this form of care. Clinical, sociodemographic and physician characteristics play an important role in treatment selection.

Introduction: The benefit of partial nephrectomy (PN) compared to radical nephrectomy (RN) for T1a renal cell carcinoma (RCC) remains uncertain, with observational studies conflicting with level 1 evidence. Therefore, the purpose of this population-based study was to compare long-term outcomes in patients undergoing PN or RN for T1a RCC. Methods: We studied 5670 patients in Ontario, Canada undergoing PN or RN for T1a RCC. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS), chronic kidney disease (CKD), end-stage renal disease (ESRD), and myocardial infarction (MI). We used multivariable Cox proportional hazard models to evaluate the association between PN or RN and these outcomes. A sensitivity analysis was performed in patients with a preoperative serum creatinine available. Results: Median followup was 77 months. Compared to RN, PN was associated with significantly improved OS (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.63–0.84), reduced risk of CKD (HR 0.18; 95% CI 0.12–0.27) and improved CSS (HR 0.45; 95% CI 0.30–0.65). The risk of myocardial infarction was not significantly different between groups (HR 0.91; 95% CI 0.62–1.34). Few patients (n=15) required renal replacement therapy. In the sensitivity analysis, the association between type of surgery and OS and CKD persisted, while the association with CSS did not. Conclusions: Our study found that in patients undergoing surgery for T1a RCC, PN was associated with improved OS and reduced risk of CKD compared to RN. However, few patients in either group developed ESRD requiring renal replacement therapy.

INTRODUCTION AND OBJECTIVE:Active surveillance (AS) is a widely accepted management strategy for low-risk prostate cancer (PC), but limited data exist regarding long-term outcomes after initial AS ...

INTRODUCTION AND OBJECTIVE:Active surveillance (AS) has become widely accepted as the standard of care for low-risk prostate cancer (PC) worldwide.. However limited work has examined the population...

Introduction: Active surveillance (AS) is an accepted management strategy for low-risk prostate cancer (PCa), but its role in the management of favorable intermediate-risk PCa remains controversial. Most reports studying the role of AS for these men generally lack long-term followup and include small numbers of patients. Our objective was to report the outcomes of men diagnosed with Gleason grade groups (GGG) 2 and 3 PCa who were managed expectantly. Methods: Using administrative datasets and pathology reports, we identified all men who were diagnosed with GGG 2 and 3 PCa and managed expectantly between 2002 and 2011 in Ontario, Canada. Outcomes and associated factors were estimated using cumulative incidence function methods and multivariable Cox regression models, respectively. Results: We identified 926 men who were managed expectantly (AS [n=374] or watchful waiting [n=552]). The eight-year cancer-specific survival was 94% and 89% for the AS and watchful waiting cohorts, respectively. Among AS men, 266 (71%) received treatment after a followup of approximately eight years. Cumulative AS discontinuation rates at one and five years were 30.5% and 65.1%, respectively. Conclusions: Expectant management of GGG 2 and 3 PCa may be an option for certain men. Notably for AS patients, the cancer-specific mortality at eight years was 6%, and over 65% of men underwent treatment within five years. Further studies are required to evaluate which patients, based on disease-specific features and competing health risks, would benefit the most from a conservative strategy.

Renal tumor biopsies have been proposed as a management alternative to avoid treatment of benign or low risk small renal masses. However, many urologists are reluctant to recommend renal tumor biopsy because they feel its result frequently will not impact management. Our primary objective was to evaluate if centers that routinely favor renal tumor biopsy have lower rates of benign histology after surgery than centers where a selective renal tumor biopsy approach is used.This was a retrospective multicenter study of patients who underwent partial or radical nephrectomy for a lesion suspicious for localized renal cell carcinoma which measured 4 cm or less (cT1a and pT1a or pT3a) between 2013 and 2015. A logistic regression model was used to examine whether the odds of obtaining a benign tumor following surgery differed between centers that routinely favor renal tumor biopsy and centers where a selective renal tumor biopsy approach is used.A total of 542 small renal masses in 516 patients were included in study. The rate of histologically benign tumors after surgery was 11%. This rate was significantly lower at centers that routinely favor renal tumor biopsy than at centers where a selective renal tumor biopsy approach is used (5% vs 16%, p 0.001). On multivariable analysis older age, smaller tumors and centers where a selective renal tumor biopsy approach is used were significantly associated with greater odds of finding a histologically benign tumor postoperatively. Compared to centers that routinely favor renal tumor biopsy the odds of finding a benign tumor at surgery was 4 times more likely at centers where a selective renal tumor biopsy approach is used (OR 4.1, 95% CI 1.9-8.3).Routine renal tumor biopsy reduces surgery for benign tumors and the potential for short-term and long-term morbidity associated with these procedures. This study suggests that routine renal tumor biopsy may be a valuable tool to decrease overtreatment of small renal masses.

Purpose To describe and compare outcomes in men with initially presumed indolent prostate cancer receiving definitive radiation therapy after active surveillance (AS) versus those in a risk-matched cohort undergoing up-front radiation therapy. Methods and Materials Men prospectively enrolled in an AS program between 1992 and 2014 and subsequently undergoing curative radiation therapy (ie, image guided radiation therapy [IGRT] or low-dose-rate brachytherapy [LDR-BT]) were identified. Biochemical relapse–free rate (bRFR), metastasis-free rate (mFR), and overall survival (OS) were compared against a cohort of men treated up front, matched by age, clinical prognostic indices (risk group, prostate-specific antigen, cT category, Gleason score, percentage of involved biopsy cores), and radiation therapy modality. Results Of 1070 patients in the AS registry, 200 underwent definitive radiation therapy (143 IGRT and 57 LDR-BT) after a median of 32.9 (interquartile range [IQR] 20.6-59.8) months on surveillance. Main reasons for treatment were grade and volume upgrading (57.5% and 26%, respectively). Median follow-up after radiation therapy was 4.9 (IQR 3.1-7.5) years. At 5 years the bRFR, mFR, and OS were, respectively, 97%, 99%, and 98.5%. No patient died of prostate cancer. Adequate risk-matching was confirmed in an independent cohort comprising 359 patients receiving up-front IGRT (71%) or LDR-BT (29%) and followed for a median of 9 (IQR 3.1-7.5) years. There was no difference in the disease-specific outcomes (bRFR, mFR) between the 2 cohorts (Gray's P value of .257 and .934, respectively). In multivariate analyses, timing of radical radiation therapy (deferred vs up-front) was not correlated to biochemical relapse or metastases occurrence. Conclusions Curative-intent radiation therapy (ie, dose-escalated IGRT or LDR-BT) after a period of AS renders excellent oncologic outcomes at 5 years. Deferring radical therapy after a period of AS does not seem to result in inferior oncologic outcomes compared with patients with similar risk characteristics undergoing up-front treatment.

We reviewed various existing active surveillance criteria and determined the competing trade-offs of the stricter vs more inclusive active surveillance criteria.Men enrolled in an active surveillance program at Princess Margaret Cancer Centre between 1998 and 2014 were identified through a prospectively maintained database. All patients were assessed for entry eligibility into the Prostate Cancer Research International: Active Surveillance, Johns Hopkins, University of Miami, University of California San Francisco, Memorial Sloan Kettering Cancer Center, University of Toronto-Sunnybrook and Royal Marsden protocols. The 2-sided t-test, ANOVA, Wilcoxon rank sum or chi-square tests were used for comparison as appropriate.Of the 1,365 men identified 1,085 met the Princess Margaret Cancer Centre inclusion criteria. When the Johns Hopkins, Prostate Cancer Research International: Active Surveillance and University of Miami criteria were applied 15.2%, 11.5% and 11.3% of these patients were excluded from active surveillance, respectively. No significant differences were noted between men who met the Princess Margaret Cancer Centre criteria and those who were excluded based on more stringent criteria when grade or volume reclassification was compared. No significant differences in prostate specific antigen velocity or the number of patients who proceeded to seek treatment were noted (p0.1). Rates of biochemical recurrence among patients who chose to undergo radical prostatectomy after initial active surveillance were not different between men who met the more inclusive vs more exclusive active surveillance protocols.More selective criteria do not significantly improve short-term outcomes when considering the relative risk of grade reclassification or biochemical failure after treatment. In an era of increased awareness regarding the over diagnosis and overtreatment of prostate cancer, we believe that stricter entry criteria should be reconsidered.

INTRODUCTION AND OBJECTIVES:Prostate cancer is the most common solid organ cancer among North American men. Traditionally, men diagnosed with prostate cancer were offered treatments in the form of ...

INTRODUCTION AND OBJECTIVES:Despite strong safety and accuracy data, renal biopsy utilization remains low. Proponents of no-biopsy argue that “it would not change management” since biopsy cohorts u...

We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance.A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy.A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p0.0001).While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.

Introduction: Radiographic imaging is used to monitor disease progression for men with metastatic castrate-resistant prostate cancer (mCRPC). The optimal frequency of imaging, a costly and limited resource, is not known. Our objective was to identify predictors of radiographic progression to inform the frequency of imaging for men with mCRPC. Methods: We accessed data for men with chemotherapy-naive mCRPC in the abiraterone acetate plus prednisone (AA-P) group of a randomized trial (COU-AA-302) (n=546). We used Cox proportional hazards modelling to identify predictors of time to progression. We divided patients into groups based on the most important predictors and estimated the probability of radiographic progression-free survival (RPFS) at six and 12 months. Results: Baseline disease and change in prostate-specific antigen (PSA) at eight weeks were the strongest determinants of RPFS. The probability of RPFS for men with bone-only disease and a ≥50% fall in PSA was 93% (95% confidence interval [CI] 87–96) at six months and 80% (95% CI 72–86) at 12 months. In contrast, the probability of RPFS for men with bone and soft tissue metastasis and

The primary goal of active surveillance (AS) is to prevent overtreatment by selecting patients with low-risk prostate cancer (PCa) and closely monitoring them so that definitive treatment can be offered when needed. With the increasing popularity of AS as a management strategy for men with localized PCa, it is important to understand all the contemporary guidelines and criteria that exist for AS and the differences among them. No single optimal management strategy for clinically localized, early-stage disease has been universally accepted. The implementation of AS varies widely between institutions, from inclusion criteria to follow-up protocols, with the most notable differences seen in maximum accepted Gleason score, T-stage and prostate-specific antigen (PSA) parameters. The objectives of this review were to systematically summarize the current literature on AS strategy, present an overview of the various published guidelines and criteria that are used for AS at several major institutions as well as discuss goals and trade-offs of the various criteria. A comprehensive search of the PubMed and Embase databases from 1990 to 2017 was performed to identify studies pertaining to AS criteria and trends. Trends in AS uptake and use in Canada, USA and Europe were reviewed to demonstrate the current trends and outcomes of AS to offer greater insight into the differences, nature and efficacy of various AS protocols. AS is a compelling antidote to the current PCa overtreatment phenomena; however, when considering patients for AS it is important to understand the differences between protocols, and review published results to appreciate the impact on follow-up.

Introduction: Renal tumour biopsies (RTBs) can provide the histology of small renal masses (SRMs) prior to treatment decisionmaking. However, many urologists are reluctant to use RTB as a standard of care. This study characterizes the current use of RTB in the management of SRMs and identifies barriers to a more widespread adoption.Methods: A web-based survey was sent to members of the Canadian and Quebec Urological Associations who had registered email address (n=767) in June 2016. The survey examined physicians’ practice patterns, RTB use, and potential barriers to RTB. Chi-squared tests were used to assess for differences between respondents.Results: The response rate was 29% (n=223), of which 188 respondents were eligible. A minority of respondents (12%) perform RTB in >75% of cases, while 53% never perform or perform RTB in

Aims Treatments and disease burden of metastatic castration-resistant prostate cancer (mCRPC) considerably affect a patient's quality of life. However, patient-reported symptom burden data are still largely insufficient. This study sought to compare the self-reported symptom burden of men with chemotherapy-naive (CN) mCRPC treated with abiraterone acetate (AA) or enzalutamide (EZ) in routine clinical practice. Materials and methods Between 2011 and 2015, 189 CN-mCRPC patients who had received AA ( n = 76) or EZ ( n = 113) at the Princess Margaret Cancer Centre were included. The Edmonton Symptom Assessment System (ESAS) score, baseline demographic information, comorbidities, Eastern Cooperative Oncology Group performance status, laboratory data and narcotic analgesic use were recorded for each patient. The minimal clinically important difference was assessed using ±1 point change from baseline for each ESAS symptom. Mixed model for repeated measures (MMRM) was used to estimate and compare the longitudinal ESAS score changes from baseline in AA and EZ groups adjusted for age, baseline ESAS scores, treatment group, treatment duration and time. Results The median (interquartile range) treatment duration with AA and EZ was 10 (6–16) and 12 (7–18) months, respectively ( P = 0.19). Fatigue was rated the most distressing symptom at baseline and following treatment in both groups. There were no statistically significant differences in the proportion of patients with clinically meaningful symptom improvement or worsening after AA or EZ administration in any of the ESAS-based physical and psychological symptoms over time. In MMRM analyses, there were no significant differences in adjusted mean scores from baseline to 3, 6, 9 and 12 months for any of the ESAS items between AA and EZ groups. Conclusion Physical and psychological symptoms assessed by ESAS were comparable in CN-mCRPC men treated with AA or EZ in the real-world clinical setting. Further studies are warranted to confirm these findings.

Abnormal maternal inflammation leads to TNF-mediated fetal growth restriction and some features of preeclampsia that can be ameliorated with the nitric oxide mimetic nitroglycerin., Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5–16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications.

with detailed and validated clinicopathologic data for all patients with newly-diagnosed CaP. For this analysis, we identified all men who underwentRP for clinically low-riskCaP (defined as clinical stage T1 or T2a, prostate specific antigen (PSA)

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is an increasingly accepted strategy for patients with low risk, low grade prostate cancer (PCa). Although differences in inclusion criteria exist, high volume Gleason 6 and higher grade of disease are commonly excluded. Yet, no consensus has been established concerning indicators of progression and uncertainties as to when patients should seek more aggressive treatment persist. Some postulate that Gleason 6 PCa has an indolent course and that only Gleason 7 should be considered a histologic trigger to treat. We aimed to elucidate the outcomes of patients who developed increased volume of Gleason 6 PCa ( 4 cores or 50% of core involved) while on AS and compared their risk of later grade progression to those who did not experience volume progression. METHODS: A prospectively maintained database was utilized to identify a total of 555 patients, median age 62.4, who were on AS with Gleason 6 disease between 2008 and 2013. Patients who demonstrated volume progression only at biopsy 2 (B2), biopsy 3 (B3), or biopsy 4+ (B4+) were studied. Univariate statistics were used for comparison. For the purposes of the current work, the endpoint of study was the development of grade progression whether it be grade only or grade + volume at the event biopsy. RESULTS: A total of 70 patients demonstrated volume progression at or after their second or confirmatory biopsy (B2). Mean follow-up was 3.67 years. In comparison to those never experiencing volume or grade progression, the mean age was 62.9 years vs. 62.1(p-value1⁄40.33), respectively. Mean PSA at diagnosis was not significantly different (p-value1⁄40.84), but median prostate volume was significantly smaller in patients who demonstrated volume progression (p-value

Introduction: Active surveillance (AS) is a strategy for the management of low-risk prostate cancer (PCa). However, few studies have assessed the uptake of AS at a population level and none of thesewere based on a Canadian population. Therefore, our objectives were to estimate the proportion of men being managed by AS in Ontario and to assess the factors associated with its uptake.Methods: This was a retrospective, population-based study using administrative databases from the province of Ontario to identify men ≤75 years diagnosed with localized PCa between 2002 and 2010. Descriptive statistics were used to estimate the proportion of men managed by AS, whereas mixed models were used to assess the factors associated with the uptake of AS.Results: 45 691 men met our inclusion criteria. Of these, 18% were managed by AS. Over time, the rates of AS increased significantly from 11% to 21% (p

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e16540Background: Reliable evaluation of the disease burden throughout advanced PC is crucial to the assessment of treatment effectiveness and patient improvement. This study sought to further expl...

92 Background: The role of 5α-reductase inhibitors (5-ARIs) in prostatic diseases remains controversial because of an FDA black box label. We have previously published on the impact of 5-ARIs in men managed with active surveillance (AS), demonstrating their protective effect against progression. However, the long-term safety of 5-ARIs in the setting of AS has never been described, thus we sought to assess this. Methods: This is a single-institution, prospectively maintained, retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on AS for PCa. Pathologic progression was evaluated and defined as Gleason score > 6, maximum core involvement > 50%, or more than 3 cores positive on a follow-up prostate biopsy. Time dependent covariate analysis to account for time on AS but not on 5-ARI was conducted to diminish the likelihood of overestimating the benefit. To account for differences in prostate volume at baseline between 5-ARI and non-5-ARI groups sensitivity analyses were performed, restricting men in the non-5-ARI group to those with larger glands (volume > 40 ml). Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression. Results: The original cohort of 288 men on AS were analyzed. The median follow-up was 61.2 months (IQR: 29.8-95.24) with 124 men (43%) experiencing pathologic progression and 119 men (41.3%) abandoning AS. Men taking a 5-ARI experienced a lower rate of pathologic progression (24.3% vs 49.1%; p < 0.001) and were less likely to abandon AS (25.7% vs 46.3%; p = 0.002). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (HR: 2.56; 95% confidence interval, 1.32-5.02). Sensitivity analyses done to account for gland size demonstrated that lack of 5-ARI use was still predictive of progression (HR: 2.76; CI, 1.45–5.25; p = 0.002). Importantly, 5-ARI use was not associated with increased risk of high-grade prostate cancer. Conclusions: 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of AS in men with median follow-up of 5 years.