Background African American (AA) men suffer a higher prostate cancer (PCa) burden than other groups. Objective We aim to determine the impact of race on the risk of upgrading, upstaging, and positive surgical margins (PSM) at radical prostatectomy (RP) among men eligible for active surveillance. Design, setting, and participants We studied men with low-risk PCa treated with RP at two centers. Low clinical risk was defined by National Comprehensive Cancer Network criteria. Outcome variables were upgrading, upstaging, and PSMs at surgery. Associations between race and the outcomes were evaluated with logistic regression adjusted for age, relationship status, diagnostic prostate-specific antigen level, percentage of positive biopsy cores, surgical approach, year of diagnosis, and clinical site. Results and limitations Of 9304 men diagnosed with PCa, 4231 were low risk and underwent RP within 1 yr. Men were categorized as AA (n = 273; 6.5%), Caucasian (n = 3771; 89.1%), or other racial/ethnic group (Other; n = 187; 4.4%). AA men had a significantly younger mean age (58.7 yr; standard deviation: ±7.06), and fewer (85%) were married or had a partner. Upgrading (34%) and upstaging (13%) rates did not significantly differ among the groups. The PSM rate was significantly higher in AA men (31%) than in the Caucasian (21%) and Other (20%) groups (p < 0.01). We found an association between race group and PSM rate (p < 0.03), with higher odds of PSMs in AA men versus Caucasian men (odds ratio [OR]: 1.64; 95% confidence interval [CI], 1.08-2.47). No statistically significant associations between race and rates of upgrading and upstaging were found. This study was limited by the relatively low proportion of AA men in the cohort. Conclusions Among clinically low-risk men who underwent RP, AA men had a higher likelihood of PSMs compared with Caucasian men. We did not find statistically significantly different rates of upgrading and upstaging between the race groups. Patient summary We analyzed two large groups of men with what appeared to be low-risk prostate cancer based on the initial biopsy findings. The likelihood of finding worse disease (higher grade or stage) at the time of surgery was similar across different racial groups.

Background Men aged >65 yr are less likely to receive local therapy for prostate cancer (PCa), perhaps because of concerns about quality-of-life (QOL) outcomes. Objective To describe QOL before and after PCa treatment in men of varying ages. Design, setting, and participants Participants enrolled in CaPSURE who underwent radical prostatectomy, brachytherapy, external beam radiation, androgen deprivation therapy, or active surveillance for localized PCa. Outcome measurements and statistical analysis QOL changes over time were assessed among age groups using repeated-measures mixed models adjusted for race, year, clinical risk, treatment, comorbidities, and an age-time interaction term. Differences are reported as adjusted least-square means and percentage decline. Secondary analyses evaluated age and QOL for local (prostatectomy, radiation) compared to nonlocal treatment (hormonal, surveillance). Results and limitations Older men had lower mean unadjusted pre- and post-treatment QOL scores for nearly all domains. Of the domains evaluated, adjusted mean sexual function, sexual bother, and urinary function showed greater declines from baseline to 2 yr. At 2 yr, more men <60 yr than those >70 yr experienced declines in urinary function (14% vs 9%) and sexual bother (39% vs 17%). Declines in these domains were also greater for local than for nonlocal treatment. Conclusions Definitive treatment for localized disease should not be deferred for older men because of fears regarding QOL declines. Younger men should be counseled about potential post-treatment declines in QOL despite higher absolute QOL scores. Communicating these differences to patients will facilitate more appropriate treatment decision-making in men of all ages. Patient summary In this study we evaluated quality of life before and after treatment for localized prostate cancer in a diverse patient population. Declines in quality of life after treatment varied according to age and treatment. We conclude that counseling about quality of life will help patients of all ages to make more appropriate treatment decisions.

Objective To assess the ability of current nomograms to predict disease progression at repeat biopsy or at delayed radical prostatectomy (RP) in a prospectively accrued cohort of patients managed by active surveillance (AS).

Purpose

We describe the outcomes of patients with low risk localized prostate cancer who were upgraded on a surveillance biopsy while on active surveillance and evaluated whether delayed treatment was associated with adverse outcome.

Materials and methods

We included men in the study with lower risk disease managed initially with active surveillance and upgraded to Gleason score 3+4 or greater. Patient demographics and disease characteristics were compared. Kaplan-Meier curve was used to estimate the treatment-free probability stratified by initial upgrade (3+4 vs 4+3 or greater), Cox regression analysis was used to examine factors associated with treatment and multivariate logistic regression analysis was used to evaluate the factors associated with adverse outcome at surgery.

Results

The final cohort comprised 219 men, with 150 (68%) upgraded to 3+4 and 69 (32%) to 4+3 or greater. Median time to upgrade was 23 months (IQR 11-49). A total of 163 men (74%) sought treatment, the majority (69%) with radical prostatectomy. The treatment-free survival rate at 5 years was 22% for 3+4 and 10% for 4+3 or greater upgrade. Upgrade to 4+3 or greater, higher prostate specific antigen density at diagnosis and shorter time to initial upgrade were associated with treatment. At surgical pathology 34% of cancers were downgraded while 6% were upgraded. Cancer volume at initial upgrade was associated with adverse pathological outcome at surgery (OR 3.33, 95% CI 1.19-9.29, p=0.02).

Conclusions

After Gleason score upgrade most patients elected treatment with radical prostatectomy. Among men who deferred definitive intervention, few experienced additional upgrading. At radical prostatectomy only 6% of cases were upgraded further and only tumor volume at initial upgrade was significantly associated with adverse pathological outcome.

Background

The effect of practice guidelines and the European Randomised Screening for Prostate Cancer (ERSPC) and Prostate, Lung, Colorectal and Ovarian (PLCO) trials on PSA screening practices of primary-care physicians (PCPs) is unknown.

Methods

We conducted a national cross-sectional on-line survey of a random sample of 3010 PCPs from July to August 2010. Participants were queried about their knowledge of prostate cancer, PSA screening guidelines, the ERSPC and PLCO trials, and about their PSA screening practices. Factors associated with PSA screening were identified using multivariable linear regression.

Results

A total of 152 (5%) participants opened and 89 completed the on-line survey, yielding a response rate of 58% for those that viewed the invitation. Eighty percent of respondents correctly identified prostate cancer risk factors. In all, 51% and 64% reported that they discuss and order PSA screening for men aged 50-75 years, respectively. Fifty-four percent were most influenced by the US Preventative Services Task Force (USPSTF) guidelines. Also, 21% and 28% of respondents stated that their PSA screening practices were influenced by the ERSPC and PLCO trials, respectively. Medical specialty was the only variable associated with propensity to screen, with family medicine physicians more likely to use PSA screening than internists (β=0.21, P=0.02).

Conclusions

Half of the physicians surveyed did not routinely discuss PSA screening with eligible patients. The impact of the ERSPC and PLCO trials on PSA screening practices was low among US PCPs. USPSTF recommendations for PSA screening continue to be the strongest influence on PCPs' propensity to use PSA screening.

Purpose Data are limited on imaging after primary treatment of localized prostate cancer. Materials and Methods We identified 8,435 men newly diagnosed with nonmetastatic prostate cancer in 1995 to 2012 who were enrolled in CaPSURE™. Patients were followed after primary treatment with radical prostatectomy, cryosurgery, brachytherapy, external beam radiation therapy or androgen deprivation therapy. We assessed the use of bone scan, computerized tomography and magnetic resonance imaging after primary treatment. Factors associated with posttreatment outcomes (number of imaging tests, and time to first imaging and salvage treatment) were evaluated with multivariate Poisson regression and Cox proportional hazards regression. Results The incidence of posttreatment bone scan, computerized tomography and magnetic resonance imaging was 20% or less. Last posttreatment log(prostate specific antigen) was associated with multiple posttreatment imaging. Management by radical prostatectomy, cryosurgery, external beam radiation therapy or brachytherapy vs androgen deprivation therapy was associated with a lower likelihood of posttreatment imaging. Of patients who were imaged after treatment 25% with radical prostatectomy and 9% with radiation underwent imaging before prostate specific antigen failure. The 5-year salvage treatment-free survival rate was 81%. Positive findings on posttreatment imaging were associated with a higher risk of salvage treatment. Conclusions Patients treated with androgen deprivation therapy for localized disease were most likely to be imaged, primarily by bone scan. Men treated with other therapies were less likely to be imaged and tended to undergo computerized tomography. Imaging may add value to posttreatment prostate specific antigen monitoring to identify disease recurrence and progression. Further studies are needed to establish guidelines for the optimal frequency and imaging type to monitor the treatment response.

Purpose: Active surveillance to manage prostate cancer provides an alternative to immediate treatment in men with low risk prostate cancer. We report updated outcomes from a long-standing active surveillance cohort and factors associated with reclassification. Materials and Methods: We retrospectively reviewed data on all men enrolled in the active surveillance cohort at our institution with at least 6 months of followup between 1990 and 2013. Surveillance consisted of quarterly prostate specific antigen testing, repeat imaging with transrectal ultrasound at provider discretion and periodic repeat prostate biopsies. Factors associated with repeat biopsy reclassification and local treatment were determined by multivariate Cox proportional hazards regression. We also analyzed the association of prostate specific antigen density and outcomes stratified by prostate size. Results: A total of 810 men who consented to participate in the research cohort were followed on active surveillance for a median of 60 months. Of these men 556 (69%) met strict criteria for active surveillance. Five-year overall survival was 98%, treatment-free survival was 60% and biopsy reclassification-free survival was 40%. There were no prostate cancer related deaths. On multivariate analysis prostate specific antigen density was positively associated with the risk of biopsy reclassification and treatment while the number of biopsies and time between biopsies were inversely associated with the 2 outcomes (each p <0.01). When stratified by prostate volume, prostate specific antigen density remained significantly associated with biopsy reclassification for all strata but prostate specific antigen density was only significantly associated with treatment in men with a smaller prostate. Conclusions: Significant prostate cancer related morbidity and mortality remained rare at intermediate followup. Prostate specific antigen density was independently associated with biopsy reclassification and treatment while on active surveillance.

Background Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. Objective To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Design, setting, and participants Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies - a discovery prostatectomy study (n = 441), a biopsy study (n = 167), and a prospectively designed, independent clinical validation study (n = 395) - testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). Outcome measures and statistical analysis The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Results and limitations Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p < 0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p = 0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p < 0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3 + 4), for whom some providers would not consider AS. Conclusions Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Patient summary Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. © 2014 European Association of Urology.