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Clinical guidelines suggest that for low-grade, clinically localized prostate cancer, patients with higher volume of disease at diagnosis may benefit from definitive therapy, although the data remain unclear. Our objective was to determine associations between low-grade prostate cancer volume and outcomes in men managed with primary radical prostatectomy.Men with cT1-2N0/xM0/x prostate cancer, prostate specific antigen at diagnosis10 ng/mL, and Gleason grade group 1 pathology on diagnostic biopsy managed with primary radical prostatectomy were included. Outcomes were pathological upgrade at radical prostatectomy (≥Gleason grade group 2), University of California, San Francisco adverse pathology at radical prostatectomy (≥Gleason grade group 3, pT3/4, or pN1), alternate adverse pathology at radical prostatectomy (≥Gleason grade group 3, ≥pT3b, or pN1), and recurrence (biochemical failure with 2 prostate specific antigen ≥0.2 ng/mL or salvage treatment). Multivariable logistic regression models were used to estimate associations between percentage of positive cores and risk of upgrade and adverse pathology at radical prostatectomy. Multivariable Cox proportional hazards regression models were used to estimate associations between percentage of positive cores and hazard of recurrence after radical prostatectomy.A total of 1,029 men met inclusion criteria. Multivariable logistic regression models demonstrated significant associations between percentage of positive cores and pathological upgrade (OR 1.31, 95% CI 1.1-1.57,In men with Gleason grade group 1 prostate cancer, tumor volume may be associated with upgrading at radical prostatectomy, but not more clinically significant outcomes of adverse pathology or recurrence.

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

For men with clinically localized prostate cancer outcomes of continuing active surveillance (AS) after biopsy progression are not well understood. We aim to determine the impact of continuing AS and delayed definitive treatment after biopsy progression on oncologic outcomes.Participants in our prospective AS cohort (1990-2018) diagnosed with grade group (GG) 1, localized prostate cancer, with prostate specific antigen20 who were subsequently upgraded to ≥GG2, and underwent further surveillance (biopsy/imaging/prostate specific antigen) were identified. Patients were stratified by post-progression followup into 3 groups: continue AS untreated, pursue early radical prostatectomy (RP) ≤6 months, or undergo late RP within 6 months to 5 years of progression. Patients receiving other treatments were excluded. We compared characteristics between groups and examined the associations of early vs late RP with risk of adverse pathology (AP) at RP and recurrence-free survival (RFS) after RP.Of 531 patients with biopsy progression and further surveillance 214 (40%) remained untreated, 192 (36%) pursued early RP and 125 (24%) underwent late RP. Among patients who underwent early vs late RP, there was no difference in GG (p=0.15) or AP (55% vs 53%, p=0.74) rate at RP, or 3-year RFS (80% vs 87%, log-rank p=0.64) after RP. In multivariable models, only Cancer of Prostate Risk Assessment post-surgical score was associated with risk of RFS (HR=1.42 per point, 95% CI 1.24-1.64).Among patients continuing AS after biopsy progression, 60% underwent surgery within 5 years. Delayed surgery after progression was not associated with higher risk of AP or RFS. This suggests select patients may be able to safely delay treatment after progression.

PURPOSE: To evaluate the comparative effectiveness of robot-assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) in a multicenter study. MATERIALS AND METHODS: We evaluated men with localized prostate cancer at eleven high-volume academic medical centers in the United States from the PROST-QA (2003–2006) and the PROST-QA/RP2 cohorts (2010–2013) with a pre-specified goal of comparing RALP (N = 549) and ORP (N = 545). We measured longitudinal patient-reported health related quality of life (HRQOL) at pre-treatment, 2, 6, 12, and 24 months, and pathologic and peri-operative outcomes/complications. RESULTS: Demographics, cancer characteristics, and margin status were similar between surgical approaches. ORP subjects were more likely to undergo lymphadenectomy (89% vs 47%; p

Men with low risk prostate cancer on active surveillance undergo multiple biopsies over time. The long-term clinical significance of consecutively negative biopsies is not known.Men with low risk prostate cancer prospectively enrolled in an active surveillance database with at least 4 biopsies were included in the study. Exposure variables were 0, 1 or 2 consecutively negative biopsies after diagnosis. Other variables included age, prostate specific antigen, prostate specific antigen density, Gleason grade group, percent positive cores and magnetic resonance imaging findings. Outcome variables were the detection of any cancer at fourth biopsy and active treatment.A total of 514 men were included, with 112 (22%) men having 1 negative biopsy and 78 (15%) with 2 consecutively negative biopsies. Median prostate specific antigen density was lower for men with 1 negative biopsy (0.11) and consecutively negative biopsies (0.10) compared to men who never had a negative biopsy (0.13, p0.01). On univariable logistic regression higher prostate specific antigen density (OR 1.68, 95% CI 1.16-2.45) and suspicious magnetic resonance imaging lesions (OR 2.00, 95% CI 1.16-3.42) were associated with a higher likelihood of detecting cancer on fourth biopsy. On multivariable logistic regression 1 negative biopsy (OR 0.22, 95% CI 0.12-0.41) and consecutively negative biopsies (OR 0.12, 95% CI 0.06-0.24) were associated with a lower likelihood of detecting cancer at outcome biopsy. Unadjusted 10-year treatment-free survival was highest for patients with consecutively negative biopsies (84%) and 1 negative biopsy (74%) than those who had none (66%) (log rank p=0.02).Consecutively negative surveillance biopsies are correlated with favorable clinical risk factors and independently associated with subsequent negative biopsy and lower risk of active treatment.

We assessd the long-term outcomes from a large prospective cohort of men diagnosed with prostate cancer managed with active surveillance and determined the clinical prognostic factors that may predict the risk of metastases.We retrospectively reviewed data of men enrolled on active surveillance at our institution between 1990 and 2018 with low or intermediate risk disease (stage cT1-2, prostate specific antigen less than 20 ng/ml, and biopsy Grade Group [GG]1-2). Patients were classified into 3 groups by diagnostic GG and prostate specific antigen density. Primary outcome was metastatic prostate cancer detected on imaging or at prostatectomy. In addition, upgrade at surveillance biopsy, active treatment, and overall and prostate cancer specific survival outcomes were assessed. Cox proportional hazards regression models were used.A total of 1,450 men met the inclusion criteria. Median followup was 77 months (IQR 49-114). The 7-year metastasis-free survival rate was 99%. Metastases developed in 15 men at a median of 62 months (IQR 29-104), of which 69% were confined to lymph nodes. Men with GG2 had a lower metastasis-free survival rate compared to those with GG1 disease. GG2, prostate specific antigen velocity and PI-RADS® 4-5 lesions on multiparametric magnetic resonance imaging were associated with a higher risk of metastases. The 7-year prostate cancer specific survival was greater than 99%.Active surveillance seems to preserve favorable long-term prognosis, as metastases and prostate cancer specific death are rare. However, the higher risk of metastases associated with higher Gleason grade, prostate specific antigen velocity, and characteristics on multiparametric magnetic resonance imaging should be considered when selecting and counseling patients for active surveillance.

We aimed to evaluate 4KscorePatients had 1 liquid biomarker test with or without multiparametric magnetic resonance imaging. High grade prostate cancer was defined as Gleason grade group 2 or greater. The overall number of avoided biopsies (with Gleason grade 1 or less), and number of missed Gleason grade 2 or greater cancer among the biopsied patients, were determined.Of the 783 patients in the overall cohort 419 (53.5%) underwent biopsy. 4Kscore and ExosomeDx scores higher than the manufacturers' cut point were associated with PI-RADS™ scores 3 to 5 and Gleason grade 2 or greater prostate cancer. Limiting biopsy to the men with liquid biomarker scores above the manufacturers' cut point would have resulted avoiding 29.5% to 39.9% unnecessary biopsies overall, while missing 4.0% to 4.8% Gleason grade 2 or greater prostate cancer in the biopsy group. Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging if the biomarker is above the manufacturers' cut point, then followed by biopsy if the multiparametric magnetic resonance imaging is positive or if 4Kscore 20 or greater or ExosomeDx 19 or greater would have missed 4.8% to 5.6% of Gleason grade 2 or greater prostate cancer in the biopsy group while avoiding 39.4% to 43.0% biopsies and 29.5% to 39.9% multiparametric magnetic resonance imaging overall. Similar algorithms with up-front multiparametric magnetic resonance imaging followed by liquid biomarker testing for negative multiparametric magnetic resonance imaging would have missed 2.4% of Gleason grade 2 or greater prostate cancer in the biopsy group but only avoided 17.2% 19.3% biopsies overall.Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging and biopsy at certain biomarker thresholds could reduce unnecessary biopsies, multiparametric magnetic resonance imaging and overdetection of Gleason grade 1 prostate cancer.

Approximately 15% of men with newly diagnosed prostate cancer have high risk features which increase the risk of recurrence and metastasis. Better predictive biomarkers could allow for earlier detection of biochemical recurrence and change surveillance and adjuvant treatment paradigms. Circulating tumor cells are thought to represent the earliest form of metastases. However, their role as biomarkers in men with high risk, localized prostate cancer is not well defined.Two to 5 months after prostatectomy we obtained blood samples from 37 patients with high risk, localized prostate cancer, defined as stage T3a or higher, Gleason score 8 or greater, or prostate specific antigen 20 ng/ml or greater. Circulating tumor cells were enumerated using a commercial platform. Matched tumor and single circulating tumor cell sequencing was performed.Circulating tumor cells were detected in 30 of 37 samples (81.1%) with a median of 2.4 circulating tumor cells per ml (range 0 to 22.9). Patients with detectable circulating tumor cells showed a trend toward shorter recurrence time (p=0.12). All patients with biochemical recurrence had detectable circulating tumor cells. Androgen receptor over expression was detected in 7 of 37 patients (18.9%). Patients with biochemical recurrence had more circulating tumor cell copy number aberrations (p=0.027). Matched tumor tissue and single circulating tumor cell sequencing revealed heterogeneity.We noted a high incidence of circulating tumor cell detection after radical prostatectomy and shorter time to biochemical recurrence in men with a higher circulating tumor cell burden and more circulating tumor cell copy number aberrations. Genomic alterations consistent with established copy number aberrations in prostate cancer were detectable in circulating tumor cells but often discordant with cells analyzed in bulk from primary lesions. With further testing in appropriately powered cohorts early circulating tumor cell detection could be an informative biomarker to assist with adjuvant treatment decisions.

We explored the prevalence and trends of self-reported complementary and alternative medicine use among patients with prostate cancer using CaPSURE™ (Cancer of the Prostate Strategic Urologic Research Endeavor).A total of 7,989 CaPSURE participants completed questionnaires between 1996 and 2016 on the use of nearly 70 complementary and alternative medicine types. Participants were defined as users if they indicated that they had ever used complementary and alternative medicines. To evaluate trends among 7,696 patients with newly diagnosed prostate cancer we considered complementary and alternative medicine use within 24 months of diagnosis and calculated the percent change in complementary and alternative medicine use between groups defined by the year of diagnosis.Of patients with prostate cancer 56% reported complementary and alternative medicine use on at least 1 questionnaire. Multivitamin and omega-3 fatty acid use was common at 40% and 24% of patients, respectively. Compared to nonusers greater proportions of complementary and alternative medicine users were college educated, had a higher household income and lived in the West and Midwest. Median prostate specific antigen at diagnosis was 5.8 (IQR 4.4-8.4) and 6.2 ng/ml (IQR 4.7-10.1) among users and nonusers, respectively (p0.01). Between those diagnosed in 1996 to 2000 and 2011 to 2016, complementary and alternative medicine use increased 128% from 24% to 54%. When comparing participants diagnosed in 2006 to 2010 with those diagnosed in 2011 to 2016, a 108% increase was seen in supplemental vitamin D use and a -48% decrease was seen in supplemental vitamin E use.Many patients with prostate cancer reported complementary and alternative medicine use. Multivitamins and omega-3 fatty acids were commonly ingested and vitamin D use increased dramatically from 2006 to 2010 compared to 2011 to 2016. These data can guide clinical discussions and decision making such as nutritionist referral and help prioritize future research.

As enrollment in active surveillance expands, it is increasingly important to assess the potential risks of deferred treatment. We evaluated the risk of prostate specific antigen recurrence in a large cohort of men who underwent radical prostatectomy after initial active surveillance.The study included men who underwent radical prostatectomy after a period of active surveillance. At diagnosis the men had GG (Gleason Grade Group) 1 or 2, clinical T2 or less and low or intermediate risk disease. They were stratified by a composite variable of GG and the volume of high grade cores at diagnosis. Pathological characteristics and recurrence after radical prostatectomy were evaluated.Of 1,916 men enrolled in active surveillance between 1994 and 2017, 448 (23.4%) underwent deferred radical prostatectomy. Median time to radical prostatectomy was 27 months (IQR 15.5-46.5). At diagnosis 388 men (86.6%) had GG1 disease, 31 (6.9%) had GG2 disease with 1 high grade core and 29 (6.5%) had GG2 disease with 2 or more high grade cores. GG2 with 2 or more high grade cores at diagnosis was associated with an increased risk of recurrence compared to GG1 disease (HR 3.29, 95% CI 1.49-7.26, p0.01). GG2 disease with 1 high grade core did not significantly differ from GG1.Our results support the careful use of active surveillance in men with GG2 and 1 high grade core at diagnosis. Men with 2 or more high grade (GG2 or greater) cores at diagnosis may benefit from immediate treatment.

Background Active surveillance (AS) is increasingly accepted for managing low-risk prostate cancer, yet there is no consensus about implementation. This lack of consensus is due in part to uncertainty about risks for disease progression, which have not been systematically compared or integrated across AS studies with variable surveillance protocols and dropout to active treatment. Objective To compare risks for upgrading from a Gleason score (GS) of 6 or less to 7 or more across AS studies after accounting for differences in surveillance intervals and competing treatments and to evaluate tradeoffs of more versus less frequent biopsies. Design Joint statistical model of longitudinal prostate-specific antigen (PSA) levels and risks for biopsy upgrading. Setting Johns Hopkins University (JHU); Canary Prostate Active Surveillance Study (PASS); University of California, San Francisco (UCSF); and University of Toronto (UT) AS studies. Patients 2576 men aged 40 to 80 years with a GS between 2 and 6 and clinical stage T1 or T2 prostate cancer enrolled between 1995 and 2014. Measurements PSA levels and biopsy GSs. Results After variable surveillance intervals and competing treatments were accounted for, estimated risks for biopsy upgrading were similar in the PASS and UT studies but higher in UCSF and lower in JHU studies. All cohorts had a delay of 3 to 5 months in detecting upgrading with biennial biopsies starting after a first confirmatory biopsy versus annual biopsies. Limitation The model does not account for possible misclassification of biopsy GS. Conclusion Men in different AS studies have different risks for biopsy upgrading after variable surveillance protocols and competing treatments are accounted for. Despite these differences, the consequences of more versus less frequent biopsies seem to be similar across cohorts. Biennial biopsies seem to be an acceptable alternative to annual biopsies. Primary funding source National Cancer Institute.

INTRODUCTION AND OBJECTIVE:The 4K score and MRI are used as screening tools to add specificity to PSA. Here we aim to evaluate 4K and its added value when combined with prostate MRI in the detectio...

INTRODUCTION AND OBJECTIVE:Although adoption of new biomarkers and MRI has become widespread, their utility when deciding to biopsy is unclear. We aim to evaluate and compare the 4K score, SelectMD...

INTRODUCTION AND OBJECTIVE:Active surveillance (AS) is recognized as a safe management option for low-risk prostate cancer, however, its utilization varies. We aim to characterize variability in AS...

The OncotypeDx® GPS (Genomic Prostate Score®) is a 17-gene RNA expression assay intended to help guide treatment decisions in men diagnosed with prostate cancer. The PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 was developed to standardize the risk stratification of lesions identified on multiparametric prostate magnetic resonance imaging. We sought to determine whether these tests are associated with an increased risk of biopsy upgrading in men on active surveillance.We identified all patients on active surveillance at the University of California-San Francisco who had low/intermediate risk prostate cancer (prostate specific antigen 20 ng/ml or less and clinical stage T1/T2) and Gleason score 6 disease who underwent multiple biopsies and had a GPS available and/or had undergone multiparametric prostate magnetic resonance imaging with an available PI-RADS version 2 score. The primary study outcome was biopsy upgrading, defined as an increase in the Gleason score from 3 + 3 to 3 + 4 or greater, which was analyzed by Cox proportional hazards regression.Of the men 140 had only GPS test findings, 169 had only a PI-RADS version 2 score and 131 had both data. Each 5-unit increase in the GPS was associated with an increased risk of biopsy upgrading (HR 1.28, 95% CI 1.19-1.39, p0.01). PI-RADS scores of 5 vs 1-2 (HR 4.38, 95% CI 2.36-8.16, p0.01) and 4 vs 1-2 (HR 2.62, 95% CI 1.45-4.76, p0.01) were also associated with an increased risk of a biopsy upgrade. On subanalysis of patients with GPS and PI-RADS version 2 scores the GPS was associated with biopsy upgrading, adding value to the clinical covariates (partial likelihood ratio p = 0.01).A higher GPS or a PI-RADS version 2 score of 4 or 5 was associated with an increased risk of biopsy upgrading.

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

PURPOSE: We summarize the available data about the clinical and economic effectiveness of magnetic resonance imaging in the diagnosis and management of prostate cancer, and provide practical recommendations for its use in the screening, diagnosis, staging and surveillance of prostate cancer. MATERIALS AND METHODS: A panel of clinicians with expertise in the diagnosis and management of prostate cancer evaluated the current published literature on the use and effectiveness of magnetic resonance imaging for this disease. When adequate studies were available for analysis, recommendations were made on the basis of data and when adequate studies were not available, recommendations were made on the basis of expert consensus. RESULTS: At this time the data support the use of magnetic resonance imaging in patients with a previous negative biopsy and ongoing concerns about increased risk of prostate cancer. The data regarding its usefulness for initial biopsy suggest a possible role for magnetic resonance imaging in some circumstances. There is currently insufficient evidence to recommend magnetic resonance imaging for screening, staging or surveillance of prostate cancer. CONCLUSIONS: Although it adds cost to the management of prostate cancer, magnetic resonance imaging offers superior anatomic detail, and the ability to evaluate cellular density based on water diffusion and blood flow based on contrast enhancement. Imaging targeted biopsy may increase the diagnosis of clinically significant cancers by identifying specific lesions not visible on conventional ultrasound. The clinical indications for the use of magnetic resonance imaging in the management of prostate cancer are rapidly evolving.

PurposeLittle is known about patterns of local failure following radiation therapy for prostate cancer. We aimed to characterize post-radiation biopsy findings, including the treatment effect and the zonal distribution of recurrent disease after radiation therapy, in men experiencing biochemical recurrence.Materials and methodsWe identified patients who received post-radiation biopsy in the setting of biochemical recurrence following primary radiation for localized disease. Histological post-radiation biopsy results were categorized by the absence of tumor, demonstration of radiation treatment effect, failure (recurrent cancer) or a combination of treatment effect and failure. We described patterns of histological failure and compared them to the diagnostic biopsy findings.ResultsA total of 284 men underwent mapped post-radiation biopsy for biochemical recurrence. Mean age at initial diagnosis was 63 years and median prostate specific antigen was 8.2 ng/ml. Of the men 33%, 32% and 35% were classified at low, intermediate and high risk based on clinical CAPRA (Cancer of the Prostate Risk Assessment) categories. Median time to post-radiation biopsy was 61 months after treatment. Findings were negative in 4% of cases while we noted a treatment effect in 31%, failure in 45% and a combination in 20%. Failure rates were similar across sextants. Of 140 patients with mapped pretreatment and posttreatment biopsies 4% demonstrated cancer in a new location previously identified as negative. Gleason upgrading occurred in 43% of cases with 85% upgraded to 4 + 3 or higher.ConclusionsMen with rising prostate specific antigen after radiotherapy for prostate cancer most often experience recurrence in dominant tumor sites. Whether failure is due to inadequate targeting, dosing or intrinsic radiation resistance remains unknown to our knowledge. Further study is warranted.

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.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.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).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.

Purpose: Prostate cancer incidence and mortality are higher in black than in white American men. We determined whether ethnicity is an independent predictor of disease recurrence in men undergoing radical prostatectomy.Materials and Methods: We studied 1,468 patients who underwent radical prostatectomy at the University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor database, a longitudinal disease registry of patients with prostate cancer. Preoperative characteristics, including age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage, biopsy Gleason score and percent positive prostate biopsies at diagnosis were determined in each patient. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment at least 6 months after surgery. Cox proportional hazards analysis was performed to determine independent predictors of time to disease recur...

Purpose: Secondary cancer treatment is common after definitive local therapy for prostate cancer and it may be an indicator of the efficacy and cost of primary local treatment. We determined predictors of secondary cancer treatment in patients initially treated with radical prostatectomy or external beam radiation.Materials and Methods: We examined 2,336 patients in Cancer of the Prostate Strategic Urologic Research Endeavor, a longitudinal registry of patients with prostate cancer, who underwent initial treatment with radical prostatectomy (1,744) or external beam radiation (592). Patients had at least 1 month of followup and all pretreatment information was available. The percent of patients receiving secondary cancer treatment, time to secondary treatment and type of secondary treatment delivered was determined. Multivariate analysis was done to determine independent predictors of secondary cancer treatment. In patients initially treated with prostatectomy a similar analysis was performed to identify p...

Purpose: We examined the ability of sextant prostate biopsies in combination with other preoperative data to predict side and sextant site of prostate cancer extracapsular extension in a large cohort of patients.Materials and Methods: We examined 223 contemporary cases of prostate cancer managed by radical prostatectomy. Using logistic regression analysis, we determined whether patient age, Gleason score, clinical stage, prostate specific antigen, number of positive sextants, biopsy location or percent of biopsy cores positive for cancer in a sextant site, side and overall gland was predictive of location of pathological extracapsular extension into periprostatic tissue.Results: Of 41 of the 223 (18%) patients with nonorgan confined disease extracapsular extension was localized to 45 sextant sites in 36 (apex 8, mid 22, base 15) while only side of extension was known in 5. In a multivariate analysis the best predictors of the risk of extracapsular extension on a side were average percent biopsy cores posi...

Although younger men have better health related quality of life scores after radical prostatectomy, many have higher baseline function with more to lose than older men. We examined the impact of age on sexual and urinary function and bother during the first 2 years after radical prostatectomy.Participants enrolled in CaPSURE™ reported sexual and urinary scores before and after radical prostatectomy using UCLA-PCI. Repeated measures mixed models were used to compare the change in health related quality of life with time between men who were younger (age 60 years or less) and older (age greater than 60 years). Logistic regression models were used to assess associations between age and clinically meaningful health related quality of life decreases (worsening). Models were adjusted for clinical characteristics.Of 1,806 patients younger men reported higher sexual and urinary function scores at each time point and higher sexual function decrease rates at 1 year than older men (81% vs 75%, p0.01). Younger men also had higher sexual bother decrease rates 1 year (74% vs 61%, p0.01) and 2 years (62% vs 56%, p=0.02) after radical prostatectomy. On multivariate analysis age was associated with changes in sexual function and bother from baseline through 2 years (each p0.01). Younger men had higher adjusted odds of sexual function decreases at 1 year (OR 1.15/5 years, 95% CI 1.01-1.30, p=0.03) but not at 2 years. Younger age was associated with lower odds of worsening sexual bother at 2 years (OR 0.79/5 years, 95% CI 0.67-0.94, p0.01). Urinary function and bother decrease rates were similar by age. Secondary analyses of the age/health related quality of life interaction showed that men were at greater risk for health related quality of life decreases if baseline scores were above average regardless of age.Younger men reported higher sexual and urinary function overall, and experienced greater decreases in sexual function immediately after radical prostatectomy than older men. While the 2 groups experienced similar relative sexual function decreases at 2 years, younger men had worse interim decreases at 1 year. Providers should consider these findings when discussing treatment timing, particularly with younger men diagnosed with early stage, low grade disease.

Purpose: Biostatistical models to predict stage or outcome in patients with clinically localized prostate cancer with pretreatment prostate specific antigen (PSA), Gleason sum on biopsy or prostatectomy specimen, clinical or pathological stage and other variables, including ethnicity, have been developed. However, to date models have relied on small subsets from academic centers or military populations that may not be representative. Our study validates and updates a model published previously with the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE, UCSF, Urology Outcomes Research Group and TAP Pharmaceutical Products, Inc.), a large multicenter, community based prostate cancer database and Center for Prostate Disease Research (CPDR), a large military database.Materials and Methods: We validated a biostatistical model that includes pretreatment PSA, highest Gleason sum on prostatectomy specimen, prostatectomy organ confinement status and ethnicity, including white and black patients....

Purpose: We studied the methylation status of E-cadherin gene promoter in prostate cancer and its relationship with E-cadherin inactivation in prostate cancer.Materials and Methods: Seven human prostate cell lines and 35 microdissected prostate cancer specimens were analyzed for E-cadherin promoter methylation using the bisulfite genome sequencing technique. E-cadherin messenger (m)RNA expression and protein expression were also studied in prostate cell lines by reverse transcriptase-polymerase chain reaction and in prostate cancer specimens by immunostaining, respectively.Results: The overall methylation of E-cadherin promoter was evident in 14 of 20 grades III to V (70%) and in 5 of 15 grades I to II (33%) prostate cancer samples. It correlated with absent or reduced E-cadherin immunostaining. Methylation in low grade tumors was present mainly in the exon region, whereas in high grade tumors methylation was also present in the promoter region. Methylation was noted in 2 of 6 prostate cancer cell lines (...

Purpose: External beam radiotherapy may be given after radical prostatectomy as adjuvant (immediate) or therapeutic (delayed) treatment, the latter in response to evidence of disease recurrence. In patients receiving delayed radiotherapy the necessity of a positive anastomotic biopsy before treatment remains unclear. We determined whether a positive anastomotic biopsy predicted the response to radiation in this setting.Materials and Methods: We reviewed the records of 67 patients who received radiotherapy for biochemical or biopsy proved recurrent prostate cancer after radical prostatectomy. Patients underwent surgery at our institution or its affiliated hospitals, or were referred to our institution for radiotherapy. All patients had a negative metastatic evaluation before receiving radiotherapy. Biochemical failure after radiotherapy was defined as serum prostate specific antigen (PSA) 0.2 ng./dl. or greater on 2 or more consecutive occasions. Biochemical recurrence-free survival was calculated using th...

Purpose: In recent years the role of pelvic lymph node dissection before or at radical prostatectomy has been questioned. We compared the outcome of performing or omitting pelvic lymph node dissection in patients undergoing radical retropubic prostatectomy by formal decision analysis.Materials and Methods: We created a decision tree for patients undergoing radical retropubic prostatectomy that accounts for all possible branch points and outcomes. Outcome probabilities applied to the model were derived from published data. Utility values were determined for each outcome state by a panel of experts. Decision analysis was done using decision analysis computer software. Sensitivity analysis was performed to determine which elements in the model were most important and to calculate threshold values.Results: Using probability data from the literature and our assigned outcome values, decision analysis initially favored omitting pelvic lymph node dissection. Sensitivity analysis revealed that the threshold values...

Purpose: We determined the demographic and clinical profile of men who elect surveillance as the initial management of prostate cancer as well as the incidence and predictors of secondary treatment of these patients.Materials and Methods: The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is a national disease registry of patients with various stages and treatments of prostate cancer. Using this database of 4,458 men we identified 329 (8.2%) who elected surveillance as the initial management of prostate cancer. Patients choosing watchful waiting were compared to other CaPSURE participants using the chi-square test. The likelihood of treatment initiation in the watchful waiting group was calculated using the Kaplan-Meier method. After adjusting for patient age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage and total Gleason score the Cox proportional hazards regression model was used to determine significant predictors of treatment initiation.Results: Compare...

Purpose: We created and tested a decision analysis model to help determine the preferred management of a positive surgical margin(s) after radical prostatectomy.Materials and Methods: We constructed a decision tree modeling surveillance versus immediate prophylactic adjuvant radiation in patients with a positive surgical margin(s) after radical prostatectomy. Literature and institution based estimates were determined for certain factors, including the probability of undetectable prostate specific antigen (PSA) in patients followed expectantly postoperatively and those treated with immediate adjuvant radiotherapy, complications of radiotherapy after prostatectomy and probability of undetectable PSA in those treated with therapeutic radiation for detectable PSA postoperatively. A panel of experts assigned utilities to the various outcomes. Sensitivity analysis was performed to determine threshold values required to change the model outcome.Results: Using average probability estimates from a literature revie...

Purpose: We analyze biopsy and prostate specific antigen (PSA) results following cryosurgery for patients with clinically localized prostate cancer.Materials and Methods: A total of 176 patients underwent 207 cryosurgical procedures for clinically localized (stages T1 to T4) prostate cancer using a multiprobe cryosurgical device. Cancer stage was T1 in 8.7%, T2 in 30%, T3 in 59% and T4 in 2.3% of the 176 patients. Neoadjuvant androgen deprivation was delivered to 101 patients (57%). End points used to determine efficacy of the procedure included analysis of posttreatment serum PSA characteristics (nadir and nonrising status) and biopsy results (absence of cancer). Cryosurgery was considered successful if PSA reached a nadir of less than 0.5 ng./ml. and did not increase by more than 0.2 ng./ml. on 2 consecutive occasions. Mean followup for the entire group was 30.8 months, with 122 patients (60%) followed for 24 or more months and 75 (36%) followed for 36 or more months.Results: Serial PSA data was...

Purpose: We define epidemiological trends in radical prostatectomy among Medicare beneficiaries in the United States, describe related financial reimbursement to hospitals and physicians, and determine how many men received adjuvant therapy with androgen ablation or pelvic irradiation from 1991 to 1993.Materials and Methods: We examined radical prostatectomy claims from a national 5% simple random sample (688,000 men) of 1991, 1992 and 1993 data on Medicare beneficiaries from the Health Care Financing Administration. We determined rates of radical prostatectomies among patients stratified by age, race and geographical region, and measured the fraction of men who had claims submitted for postoperative therapies for prostate cancer. We also collected financial information for Medicare parts A and B to estimate federal government economic burden from radical prostatectomy in this population.Results: Among the 5,016 patients identified with Medicare claims for radical prostatectomy during 1991 to 1993...

Purpose: We evaluated prospectively the ethnic variations in prostate specific antigen (PSA) and prostate specific antigen density in the detection of carcinoma of the prostate.Materials and Methods: A total of 297 consecutive patients with an elevated serum PSA and/or abnormal digital rectal examination underwent transrectal ultrasound with lesion directed and systematic biopsy (6 if the prostatic volume was 50 cc or less and 12 if it was greater than 50 cc). Receiver operating characteristic curves, predictive values and likelihood ratios were calculated for PSA and PSA density for white and black patients. Ethnic analysis was performed for the entire group, patients with a normal digital rectal examination, and those with a normal digital rectal examination and PSA of 4 to 10 ng./ml.Results: Of the 297 patients 131 (44%) had cancer, including 48 of 97 black (50%) and 83 of 200 white (42%) patients. Median PSA, PSA density and prostate size did not differ between the positive or negative biopsy ...

Purpose: We evaluated prospectively prostate specific antigen (PSA) and prostate specific antigen density in the detection of prostate cancer in patients with normal findings on digital rectal examination with and without normal transrectal ultrasound.Materials and Methods: Consecutive patients (184) with an elevated serum PSA and normal digital rectal examination underwent transrectal ultrasound with lesion directed and systematic biopsies (6 if prostatic volume was 50 cc or less and 12 if volume was more than 50 cc). Receiver operating characteristic curves, predictive values and likelihood ratios were calculated for PSA and PSA density.Results: Of the 184 patients 50 (27 percent) with a normal digital rectal examination had cancer compared to 30 of 112 (27 percent) with a normal digital rectal examination and transrectal ultrasound. Median PSA or PSA density did not differ between the positive and negative biopsy groups among patients with a normal digital rectal examination (8.4 versus 7.1 and...

Purpose: We assessed the ability of tumor cellular proliferative fraction to predict long-term survival among patients with lymphatic metastases from prostate cancer.Materials and Methods: We studied 50 patients with stage D1 (TxN+M0) prostate cancer who underwent pelvic lymphadenectomy and125 iodine seed implantation between 1970 and 1978. We used the MIB-1 monoclonal antibody to Ki67 to stain sections of the lymphatic metastases in these patients. The Ki67 proliferative fraction was defined as the fraction of positively stained malignant nuclei. We also used flow cytometry to determine the deoxyribonucleic acid content of the lymphatic metastases.Results: Median followup was 6.1 years. Patients whose metastases had a Ki67 proliferative fraction of less than 0.1 had significantly longer survival compared to those with a proliferative fraction of greater than 0.1 (8.7 years versus 4.4 years, respectively, p = 0.005, log rank test). The Ki67 proliferative fraction and ploidy were not independent va...

We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection.The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases.There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities.Although recently published trials show different results regarding the impact of prostate cancer screening on mortality, both suggest that prostate cancer screening leads to overdetection and overtreatment of some patients. Therefore, men should be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men diagnosed with prostate cancer.

We described changes in tumor volume on serial biopsies during an extended period in men on active surveillance.The study cohort included men diagnosed with prostate cancer between 1998 and 2010 enrolled in active surveillance with 6 or more months of followup. Change in volume over time was assessed as change in percent cores positive, percent cancer in 1 biopsy core and the doubling of total cancer volume (mm). Logistic regression was used to determine the association between grade and volume progression.A total of 399 men met the study inclusion criteria. Mean patient age was 61.8 years old and 313 (78%) had low risk disease. Overall 231 (58%) men had stable disease on repeat biopsies. There were 39 (10%) men with a volume increase, defined by an increase to more than 33% cores involved or an increase in maximum single core positive to more than 50%, and there were 44 (11%) with an increase in volume and grade. Approximately 10% of men experienced a decrease in cancer volume. On multivariate analysis there was a significant association between grade and volume progression on any biopsy (OR 3.07), and a doubling of tumor length (mm) at 5 years (OR 6.30).Prostate cancer volume increases and decreases at a similar rate of 10% per biopsy. An increase in tumor volume is associated with an increase in cancer grade on early repeat biopsies. However, there is a large degree of variation in cancer volume over time.

PurposeRenal cell carcinoma is increasingly diagnosed at stage I, and among stage I cases mean tumor size has been decreasing. Previous reports suggest that nephron sparing surgery is underused for small renal cell carcinomas. We determined updated, population based treatment trends for stage I renal cell carcinoma.Materials and methodsThe National Cancer Data Base, which captures approximately 70% of all cancer diagnoses in the United States, was queried for renal cell carcinoma in adults diagnosed between 1993 and 2007. Trends in treatment, including no surgery, total nephrectomy, partial nephrectomy and focal ablation, were analyzed among all stage I tumors and small stage I tumors categorized by size. Logistic regression was used to identify predictors of nephron sparing surgery (partial nephrectomy or focal ablation).ResultsDuring the study period we identified 242,740 renal cell carcinomas, of which 127,691 were stage I. For all stage I tumors partial nephrectomy increased from 6.3% to 32.2% of cases and ablation increased from 1.0% to 6.8%. For tumors less than 2.0, 2.0 to 2.9 and 3.0 to 3.9 cm partial nephrectomy increased from 15.3% to 61.1%, 11.0% to 44.2% and 7.2% to 31.1%, respectively (each p

Bladder cancer survival is consistently lower in female and black patients than in male and white patients. We compared trends and differences according to clinical, demographic and facility characteristics by patient race and gender to identify the impact of these characteristics on survival.We identified bladder transitional cell carcinoma cases diagnosed in 1993 to 2007 from the National Cancer Data Base. Trends in grade and stage distribution between 1993 and 2007 were analyzed. Survival differences by race and gender were compared using 5-year relative survival and multivariate Cox regression.There were 310,257 white male, 102,345 white female, 13,313 black male and 7,439 black female patients. Black and female patients had a higher proportion of muscle invasive tumors than white and male patients, and black patients had a larger proportion of higher grade tumors. The incidence of stage 0a and of high grade tumors significantly increased with time. Multivariate analysis showed a significantly lower HR in white females than in white males (HR 0.9) but a significantly higher HR in black males and females (HR 1.2). The higher mortality risk in black males and females was primarily limited to late stage disease (HR 1.3).Survival differences by race and gender are partially explained by differences in tumor and demographic characteristics in black males and females, and fully explained by these characteristics in white females. Treatment delays and under treatment due to comorbid conditions, age and other factors may also contribute to these disparities.

Scholarly research is considered by many to be an important component of residency training but little is known about the quantity and types of publications produced by urology residents. To our knowledge whether publication efforts during residency predict future academic publication performance is also unknown. We evaluated resident productivity, as measured by peer reviewed publication output, and determined its relation to future publication output as junior faculty.We assembled a list of graduating residents from 2002 to 2004 who were affiliated with the top 50 urology hospitals, as ranked in 2009 by U.S. NewsWorld Report. PubMed® was queried to determine the publication total in the last 3 years of residency of each individual and during years 2 to 4 after residency graduation. Resident publication output was stratified by research time and fellowship training. The relationship between resident productivity and future achievement was assessed.We assessed the publication output of 251 urologists from a total of 34 training programs affiliated with the top 50 urology hospitals. Subjects published a mean total of 3.5 and a mean of 2.0 first author papers during training. Greater research time during residency was associated with increased productivity during and after residency. Publication during training correlated with publication during the early academic career.Publication output correlated with increasing dedicated research time and was associated with the pursuit of fellowship training and an academic career. Publication during residency predicted future academic achievement.

We examined patterns of primary treatment for prostate cancer in men 75 years or older.Data were obtained from the multi-institutional CaPSURE database on the type of primary therapy performed in men younger than 75, or 75 years old or older. Primary therapy was defined as watchful waiting, radical prostatectomy, brachytherapy, brachytherapy plus external beam radiotherapy, external beam radiotherapy or primary androgen deprivation therapy. The chi-square test and multinomial logistic regression analysis were performed to identify predictors of the type of primary therapy and outcomes.A greater proportion of patients 75 years or older were white, single, had multiple comorbidities, low income and low education, and were classified as being at high risk compared to those younger than 75 years (43% vs 25%). On multivariate analysis adjusted for sociodemographic factors, diagnostic risk category and the number of comorbidities at diagnosis patients 75 years or older were less likely to be treated with primary therapy than with watchful waiting regardless of the risk category or comorbidity level.Older patients with high risk cancer are far more likely to be observed regardless of the burden of comorbidity. A more tailored approach to prostate cancer therapy that considers comorbidity and functional level to determine primary therapy may be more appropriate. Well selected older patients with high risk disease, particularly those with low comorbidity levels, may derive survival benefit from a primary therapy other than watchful waiting. Alternatively elderly patients with low risk disease may be better treated with watchful waiting.

Purpose: The proportion of renal cell carcinoma cases diagnosed at stage I is known to be increasing significantly. We characterized stage I tumors further in terms of tumor size at diagnosis using a large national cancer registry. Materials and Methods: The National Cancer Data Base captures approximately 75% of all newly diagnosed cancer cases in the United States. The database was queried for all adults who were diagnosed between 1993 and 2004 with stage I renal cell carcinoma. Trends were assessed in mean size with time as well as in the proportion of stage I tumors diagnosed at less than 2.0, less than 2.5 and less than 3.0 cm. Results: There were 104,150 patients in the National Cancer Data Base diagnosed with stage I renal cell carcinoma during the study period. A total of 10,279 stage I tumors (9.9%) were less than 2.0 cm, 26,621 (25.6%) were 2.5 cm or less and 39,879 (38.3%) were 3.0 cm or less. Analysis of stage I renal cell carcinoma diagnoses with time demonstrated a statistically significant increase in the proportion of renal masses 3.0 cm or less between 1993 and 2004 (32.5% vs 43.4%). Of tumors 3.0 cm or less the proportion smaller than 2.0 cm increased significantly during the study period from 24.1% in 1993 to 29.4% in 2004. Mean tumor size decreased from 4.1 to 3.6 cm between 1993 and 2004 (p

We analyzed patterns of disease presentation and outcome of renal cell carcinomas by gender using data from the National Cancer Database during a 10-year period. We hypothesized that women presented with lower stage disease and had increased survival than men due to increased imaging.The National Cancer Database is a nationwide oncology data set that currently captures approximately 75% of all newly diagnosed cancer cases from more than 1,400 facility based cancer registries in the United States annually since 1985. The National Cancer Database was queried for adults with renal cell carcinoma diagnosed between 1993 and 2004. Cases were examined according to gender in relation to mean age, American Joint Committee on Cancer stage, histology, grade, tumor size, mortality and race.We identified a total of 236,930 patients with renal cell carcinoma diagnosed between 1993 and 2004 from the National Cancer Database. A total of 89,243 (37.7%) were female and 147,687 (62.3%) were male. Mean age was greater in females (64.3) than in males (62.9) (p0.001). Women had a higher percentage of stage I tumors (54.1% vs 48.5%, p0.001). Progressive stage migration was documented in men and women. A trend toward increased survival was noted in women relative to men that did not reach statistical significance.Results from this study show a ratio of 1.65 of renal cell carcinoma for males compared to females. Women are more likely than men to have stage I tumors. Both men and women have demonstrated stage migration, although women more so than men.