Targeted Biopsy Is Sufficient for Men on Active Surveillance for Early-Stage Prostate Cancer.

PURPOSE: Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. mpMRI targeting has become a standard. It is unclear whether targeted biopsy alone reliably identifies the dominant lesion, thereby obviating the need for systematic sampling. MATERIALS AND METHODS: Participants enrolled in AS with early-stage prostate cancer (PSA < 20, cT1-2, GG1-2) and underwent 2+ systematic biopsy sessions with or without MR-targeted sampling. The findings for dominant Gleason Grade (GG) and tumor localization were assessed. RESULTS: Among 821 men who underwent MR fusion biopsies, 82% were diagnosed with GG1 and 18% with GG2. Sixty-two percent had their first MR fusion biopsy as diagnostic or confirmatory. Across all fusion biopsies, MRI-targeted detection of GG and/or tumor location overlapped with systematic sampling for 95% of cases. For 5% of cases, systematic biopsy was unique in detecting GG and location outside the target. Most unique lesions detected outside the target had marginally aggressive features: 73% GG2 of low-volume and favorable histologic subtypes. CONCLUSIONS: In men with MR fusion biopsies, targeting alone identified the dominant GG and location most of the time (95%); 25% of dominant lesions were contiguous to the target, suggesting that better sampling of the target improves detection. The remaining 5% of men had higher-grade, low-volume disease outside the targeted lesion of which only 2% had aggressive risk features. MR fusion targeting, without systematic sampling, may be sufficient to monitor men on AS. Few high-risk cancers are missed, all of limited volume and favorable histology.

Representation Matters: Trust in Digital Health Information Among Black Patients With Prostate Cancer.

PURPOSE: Although the majority of US adults obtain health information on the internet, the quality of information about prostate cancer is highly variable. Black adults are underrepresented in online content about prostate cancer despite a higher incidence of and mortality from the disease. The goal of this study was to explore the perspectives of Black patients with prostate cancer on the importance of racial representation in online content and other factors influencing trust. MATERIALS AND METHODS: We conducted 7 virtual focus groups with Black patients with prostate cancer in 2022 and 2023. Participants completed an intake questionnaire with demographics followed by a group discussion, including feedback on purposefully selected online content. Transcripts were independently analyzed by 2 investigators experienced in qualitative research using a constant comparative method. RESULTS: Most participants use online sources to look for prostate cancer information. Racial representation is an important factor affecting trust in the content. A lack of Black representation has consequences, including misperceptions about a lower risk of prostate cancer and discouraging further information-seeking. Other key themes affecting trust in online content included the importance of a reputable source of information, professional website structure, and soliciting money. CONCLUSIONS: Underrepresentation of Black adults in prostate cancer content has the potential to worsen health disparities. Optimal online communications should include racially diverse representation and evidence-based information in a professional format from reputable sources without financial conflict.

PSA density does not improve predictive accuracy of the UCSF-CAPRA score.

INTRODUCTION: The University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score is a validated tool using factors at diagnosis to predict prostate cancer outcomes after radical prostatectomy (RP). This study evaluates whether substitution of prostate-specific antigen (PSA) density for serum PSA improves predictive performance of the clinical CAPRA model. METHODS: Participants were diagnosed in 2000-2019 with stage T1/T2 cancer, underwent RP, with at least a 6-month follow-up. We computed standard CAPRA score using diagnostic age, Gleason grade, percent positive cores, clinical T stage, and serum PSA, and an alternate score using similar variables but substituting PSA density for PSA. We reported CAPRA categories as low (0-2), intermediate (3-5), and high (6-10) risk. Recurrence was defined as two consecutive PSA ≥ 0.2 ng/mL or receipt of salvage treatment. Life table and Kaplan-Meier analysis evaluated recurrence-free survival after prostatectomy. Cox proportional hazards regression models tested associations of standard or alternate CAPRA variables with recurrence risk. Additional models tested associations between standard or alternate CAPRA score with recurrence risk. Cox log-likelihood ratio test (-2 LOG L) assessed model accuracy. RESULTS: A total of 2880 patients had median age 62 years, GG1 30% and GG2 31%, median PSA 6.5, and median PSA density 0.19. Median postoperative follow-up was 45 months. Alternate CAPRA model was associated with shifts in risk scores, with 16% of patients increasing and 7% decreasing (p < 0.01). Recurrence-free survival after RP was 75% at 5 years and 62% at 10 years. Both CAPRA component models were associated with recurrence risk after RP on Cox regression. Covariate fit statistics showed better fit for standard CAPRA model versus alternate (p < 0.01). Standard (hazard ratio [HR]: 1.55; 95% confidence interval [CI]: 1.50-1.61) and alternate (HR: 1.50; 95% CI: 1.44-1.55) CAPRA scores were associated with recurrence risk, with better fit for standard model (p < 0.01). CONCLUSIONS: In a 2880 patient cohort followed for median 45 months after RP, alternate CAPRA model using PSA density was associated with higher biochemical recurrence (BCR) risk, but performed inferior to standard CAPRA at predicting BCR. While PSA density is an established prognostic variable in prediagnostic settings and sub-stratifying low-risk disease, it does not improve BCR model predictive accuracy when applied across a range of cancer risk.

Stability of Prognostic Estimation Using the CAPRA Score Incorporating Imaging-based vs Physical Exam-based Staging.

PURPOSE: Although official T-staging criteria for prostate cancer are based on digital rectal examination findings, providers increasingly rely on transrectal US and MRI to define pragmatic clinical stage to guide management. We assessed the impact of incorporating imaging findings into T-staging on performance of a well-validated prognostic instrument. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for prostate cancer diagnosed between 2000 and 2019 with stage ≤cT3a on both digital rectal examination and imaging (transrectal US/MRI) were included. The University of California, San Francisco CAPRA (Cancer of the Prostate Risk Assessment) score was computed 2 ways: (1) incorporating digital rectal examination-based T stage and (2) incorporating imaging-based T stage. We assessed for risk changes across the 2 methods and associations of CAPRA (by both methods) with biochemical recurrence, using unadjusted and adjusted Cox proportional hazards models. Model discrimination and net benefit were assessed with time-dependent area under the curve and decision curve analysis, respectively. RESULTS: Of 2,222 men included, 377 (17%) increased in CAPRA score with imaging-based staging (P < .01). Digital rectal examination-based (HR 1.54; 95% CI 1.48-1.61) and imaging-based (HR 1.52; 95% CI 1.46-1.58) CAPRA scores were comparably accurate for predicting recurrence with similar discrimination and decision curve analyses. On multivariable Cox regression, positive digital rectal examination at diagnosis (HR 1.29; 95% CI 1.09-1.53) and imaging-based clinical T3/4 disease (HR 1.72; 95% CI 1.43-2.07) were independently associated with biochemical recurrence. CONCLUSIONS: The CAPRA score remains accurate whether determined using imaging-based staging or digital rectal examination-based staging, with relatively minor discrepancies and similar associations with biochemical recurrence. Staging information from either modality can be used in the CAPRA score calculation and still reliably predict risk of biochemical recurrence.

Gleason Grade 1 Prostate Cancer Volume at Biopsy Is Associated With Upgrading but Not Adverse Pathology or Recurrence After Radical Prostatectomy: Results From a Large Institutional Cohort.

PURPOSE: 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. MATERIALS AND METHODS: Men with cT1-2N0/xM0/x prostate cancer, prostate specific antigen at diagnosis <10 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. RESULTS: 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, P < .01), but not University of California, San Francisco adverse pathology at radical prostatectomy (P = .84); percentage of positive cores was negatively associated with alternate adverse pathology (OR 0.67, 95% CI 0.48-0.93, P = .02). Multivariable Cox regression models demonstrated no association between percentage of positive cores and hazard of recurrence after radical prostatectomy (P = .11). CONCLUSIONS: 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.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Androgen Deprivation Therapy and the Risk of Dementia after Treatment for Prostate Cancer.

PURPOSE: The association between androgen deprivation therapy (ADT) and dementia in men with prostate cancer remains inconclusive. We assessed the association between cumulative ADT exposure and the onset of dementia in a nationwide longitudinal registry of men with prostate cancer. MATERIALS AND METHODS: A retrospective analysis of men aged ≥50 years from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry was performed. The primary outcome was onset of dementia after primary treatment. ADT exposure was expressed as a time-varying independent variable of total ADT exposure. The probability of receiving ADT was estimated using a propensity score. Cox proportional hazards regression was performed to determine the association between ADT exposure and dementia with competing risk of death, adjusted for propensity score and clinical covariates among men receiving various treatments. RESULTS: Of 13,570 men 317 (2.3%) were diagnosed with dementia after a median of 7.0 years (IQR 3.0-12.0) of followup. Cumulative ADT use was significantly associated with dementia (HR 2.02; 95% CI 1.40-2.91; p <0.01) after adjustment. In a subset of 8,506 men, where propensity score matched by whether or not they received ADT, there was also an association between ADT use and dementia (HR 1.59; 95% CI 1.03-2.44; p=0.04). There was no association between primary treatment type and onset of dementia in the 8,489 men in the cohort who did not receive ADT. CONCLUSIONS: Cumulative ADT exposure was associated with dementia. This increased risk should be accompanied by a careful discussion of the needs and benefits of ADT in those being considered for treatment.

The Natural History of Untreated Biopsy Grade Group Progression and Delayed Definitive Treatment for Men on Active Surveillance for Early-Stage Prostate Cancer.

PURPOSE: 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. MATERIALS AND METHODS: Participants in our prospective AS cohort (1990-2018) diagnosed with grade group (GG) 1, localized prostate cancer, with prostate specific antigen <20 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. RESULTS: 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). CONCLUSIONS: 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.

Natural history of an immediately detectable PSA following radical prostatectomy in a contemporary cohort.

BACKGROUND: A detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) is an unfavorable prognostic factor. However, not all men with a detectable PSA experience recurrence. We describe the natural history and outcomes in men with a detectable PSA following RP in a contemporary cohort. METHODS: A retrospective analysis of men who underwent RP for non-metastatic prostate cancer at the University of California, San Francisco from 2000 to 2020 was performed. A detectable PSA was defined as PSA ≥ 0.03 ng/ml within 6 months of RP. Cox regression models tested the effect of detectable PSA on the development of metastasis, prostate cancer-specific mortality, and overall survival. RESULTS: We identified 2941 men who had RP with 408 (13.9%) with a detectable PSA within the first 6 months. The median follow-up was 4.42 years (interquartile range [IQR], 2.58-8.00). In total, 296 (72.5%) men with a detectable PSA had salvage treatment at a median of 6 months (IQR, 4-11). One hundred sixteen of these men had PSA failure after salvage treatment at a median of 2.0 years (IQR, 0.7-3.8). On multivariable Cox regression, the risk of development of metastasis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = .01), prostate cancer-specific mortality (HR, 1.13; 95% CI, 1.05-1.21; p = .0005), and overall mortality (HR, 1.07; 95% CI, 1.03-1.12; p = .002) was associated with PSA velocity after salvage treatment in men with a detectable PSA. CONCLUSIONS: Men with a detectable PSA after RP may have excellent long-term outcomes. PSA velocity after salvage treatment may be an important predictor for the development of metastasis, prostate cancer-specific mortality, and overall mortality.

Influence of pelvic lymph node dissection and node-positive disease on biochemical recurrence, secondary treatment, and survival after radical prostatectomy in men with prostate cancer.

BACKGROUND: The benefit of pelvic lymph node dissection (PLND) at radical prostatectomy (RP) remains unclear given the low prevalence of known nodal disease (pN1) and concerns about its therapeutic utility. OBJECTIVE: To characterize the impact of PLND and secondary treatment on oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of men who underwent primary RP with PLND for prostate cancer (PCa) at our institution since 2003. Men stratified by nodal status. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Outcomes include biochemical recurrence-free survival (bRFS), overall survival, and PCa-specific mortality (PCSM). Multivariable Cox regression models used for each outcome. RESULTS AND LIMITATIONS: Of 1,543 men who underwent primary RP, 174 (11%) had pN1 disease. Median follow-up was 34 months (interquartile range, 15-62). Seven-year outcomes were similar whether less than or ≥14 LNs dissected. Among node-positive patients, 29% had undetectable (UDT) prostate-specific antigen (PSA), 11% had UDT PSA + adjuvant therapy, and 60% had detectable PSA, and 7-year bRFS differed (75% for UDT PSA, 90% for UDT + adjuvant therapy, 38% for detectable PSA, p < .01). Survival outcomes did not differ. In multivariable analysis, detectable PSA (vs. UDT, HR 5.2, 95% CI 2.0-13.3) associated with worse bRFS. After salvage treatment, 7-year outcomes did not differ between groups. Study limited by retrospective review.

The Clinical Significance of Multiple Negative Surveillance Prostate Biopsies for Men on Active Surveillance-Does Cancer Vanish or Simply Hide?

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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, p <0.01). 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). CONCLUSIONS: Consecutively negative surveillance biopsies are correlated with favorable clinical risk factors and independently associated with subsequent negative biopsy and lower risk of active treatment.

Residual Benign Prostate Glandular Tissue after Radical Prostatectomy is Not Associated with the Development of Detectable Postoperative Serum Prostate Specific Antigen.

PURPOSE: To determine if benign glandular tissue at the surgical margin (BGM) is associated with detectable prostate specific antigen (PSA) and/or biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: Participants underwent RP for localized prostate cancer between 2004 and 2018. Regression analysis was used to identify demographic, clinical and surgical factors associated with the likelihood of BGM presence on surgical pathology. Oncologic outcomes included detectable PSA (>0.03 ng/ml), BCR (≥0.2 ng/ml) and progression to BCR or salvage treatment after detectable PSA. Life tables and Cox proportional hazards regression models were used to determine the association of BGM and risk of oncologic outcomes. RESULTS: A total of 1,082 men underwent RP for localized prostate cancer with BGM reported on surgical pathology and an undetectable postoperative PSA. BGM was present on 249 (23%) specimens. Younger age, bilateral nerve sparing surgery and robotic approach were associated with presence of BGM while malignancy at the surgical margin (MSM) was not. At 7 years after RP, 29% experienced detectable PSA and 11% had BCR. In the subgroup of men who reached detectable PSA, 79% had progression within 7 years. On multivariate Cox proportional hazards regression, BGM status was not independently associated with detectable PSA, BCR and/or progression from detectable PSA to BCR or salvage treatment. CONCLUSIONS: The presence of BGM at RP was not associated with increased risk of MSM, detectable PSA, BCR or progression after detectable PSA.

Bladder cancer in patients younger than 40 years: outcomes from the National Cancer Database.

PURPOSE: To evaluate the clinical, pathological, and survival outcomes of bladder cancer in patients aged 18-40 years. METHODS: We identified 362,091 bladder cancer patients from the National Cancer Database between 2004-2013 and compared patients aged 18-40 years to those > 40 years of age with univariate analysis using Chi-square tests. A subset analysis was performed on patients who underwent cystectomy. Multivariable Cox regression was used for overall survival analysis. RESULTS: Our final analysis included 314,177 patients with 3314 (1.1%) patients aged 18-40 years. Patients aged 18-40 years had a lower male-to-female ratio (2.4 versus 3.0), a greater proportion of low-grade tumors (72.7% versus 48.3%, p < 0.001), non-muscle invasive tumors (90.3% versus 81.2%, p < 0.001), and variant histology (4.0% versus 3.3%, p < 0.001). Similar trends were observed at cystectomy including lower male-to-female ratio in the 18-40 years group (1.7 versus 3.1), a greater proportion of variant histology (25.0% versus 10.0%, p < 0.001); and 53.3% of those younger patients with variant histology were women. Patients aged 18-40 years who underwent cystectomy had a higher proportion of locally advanced disease (pT4 19.2% versus 14.6%, p = 0.004). Multivariable analyses in both cohorts demonstrated that variant histology was a predictor of worse overall survival. CONCLUSION: The majority of patients aged 18-40 years with bladder cancer present with low-grade, non-muscle-invasive disease associated with better survival. However, a subset of younger patients with a higher proportion of women presents with aggressive bladder cancer which may be partly explained by a higher prevalence of variant histology.

Post-Diagnostic Dietary and Lifestyle Factors and Prostate Cancer Recurrence, Progression, and Mortality.

PURPOSE OF REVIEW: This study aimed to summarize evidence published between 1999 and June 2020 examining diet and lifestyle after prostate cancer (PC) diagnosis in relation to risk of biochemical recurrence, PC progression, and PC-specific mortality. RECENT FINDINGS: Secondary prevention is an important research area in cancer survivorship. A growing number of studies have reported associations between post-diagnostic modifiable behaviors and risk of PC outcomes. Evidence on modifiable lifestyle factors and PC remains limited. Where multiple studies exist, findings are often mixed. However, studies consistently suggest that smoking and consumption of whole milk/high-fat dairy are associated with higher risk of PC recurrence and mortality. In addition, physical activity and ½ to 1 glass of red wine/day have been associated with lower risk of recurrence and PC-specific mortality. Greater inclusion of racially/ethnically diverse groups in future research is necessary to understand these relationships in populations most impacted by adverse PC outcomes.

The Long-Term Risks of Metastases in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Risk Factors for Biopsy Reclassification over Time in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: Few validated clinical tools currently exist to standardize the frequency of biopsies for men on active surveillance for low risk prostate cancer. We determined predictors of biopsy reclassification at specific time points after enrollment on active surveillance. MATERIALS AND METHODS: We identified men with clinically low risk prostate cancer prospectively enrolled on active surveillance at the University of California, San Francisco between 2000 and 2016. Biopsy reclassification was defined as Gleason Grade Group 2 or greater on subsequent biopsy. Multivariable Cox proportional hazards regression models were used to identify factors associated with risk of biopsy reclassification at first surveillance biopsy and 1 to 3, 3 to 5 and 5 to 10 years after enrollment, adjusting for clinicodemographic factors, PI-RADS® (Prostate Imaging Reporting and Data System) score and genomic testing. RESULTS: A total of 1,031 men were included in the study. On multivariable analysis biopsy reclassification was associated with prostate specific antigen density 0.15 or greater (HR 3.37, 95% CI 1.83-6.21), percentage biopsy cores positive (HR 1.27, 95% CI 1.05-1.54) and high genomic score (HR 2.81, 95% CI 1.21-6.52) at first surveillance biopsy and also at 1 to 3 years, after adjustment. Prostate specific antigen density 0.15 or greater (HR 2.36, 95% CI 1.56-3.56) and prostate specific antigen kinetics (HR 2.19, 95% CI 1.43-3.34) were associated with reclassification at 3 to 5 years. A PI-RADS 4-5 score was not associated with biopsy reclassification at any time point. CONCLUSIONS: High genomic score, prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater were associated with reclassification within 3 years of commencing active surveillance, and prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater remained associated with reclassification at 5 years after diagnosis.

MRI-Based Prostate-Specific Antigen Density Predicts Gleason Score Upgrade in an Active Surveillance Cohort.

OBJECTIVE. Elevated prostate-specific antigen density (PSAD) based on transrectal ultrasound (TRUS) measurements has been shown to be strongly associated with clinically significant disease and to predict progression on active surveillance (AS) for men with disease that is at a low stage or grade. We hypothesized that elevated MRI PSAD is similarly associated with increased risk of progression on subsequent biopsy. MATERIALS AND METHODS. In this retrospective study, men with Gleason score of 3+3 on diagnostic TRUS-guided biopsy who were managed with AS, had undergone MRI, and had at least one additional biopsy were included. MRI PSAD was calculated using prostate volume on MRI and prostate-specific antigen level temporally closest to the MRI. Multivariable logistics regression models were used to evaluate the association between MRI PSAD and predictors of upgrade on serial biopsy. RESULTS. A total of 166 patients were identified, of whom 74 (44.6%) were upgraded to a Gleason score of 7 or higher on subsequent biopsy. Lesions with Prostate Imaging Reporting and Data System (PI-RADS) scores of 4 and 5 more commonly had MRI PSAD of 0.15 ng/mL2 or higher (51.93% vs 22.22%, p = 0.01) than lesions with PI-RADS scores of 1-3. Median MRI PSAD was significantly higher in the upgraded group compared with the group that was not upgraded (0.15 ng/mL2 vs 0.11 ng/mL2, p = 0.01). MRI PSAD was significantly associated with increased odds of upgrading on subsequent biopsy (log transformation; odds ratio, 1.9 [95% CI, 1.2-2.8]; p = 0.01) after adjusting for age and length of follow-up. CONCLUSION. MRI PSAD was significantly associated with Gleason score upgrading on subsequent biopsy for men initially diagnosed with Gleason 3+3 disease. Although this result is intuitive, to our knowledge it has not been previously shown. As MRI utilization increases, MRI PSAD can aid in risk stratification for men managed with AS.

Correction to: A comparison of stage-specific all-cause mortality between testicular sex cordstromal tumors and germ cell tumors: results from the National Cancer Database.

An amendment to this paper has been published and can be accessed via the original article.

A comparison of stage-specific all-cause mortality between testicular sex cord stromal tumors and germ cell tumors: results from the National Cancer Database.

BACKGROUND: Testicular sex cord stromal tumors (SCSTs) are managed similarly to germ cell tumors (GCTs); however, few studies have directly compared outcomes between these tumor types. Using the National Cancer Database (NCDB), we sought to compare overall and stage-specific all-cause mortality (ACM) between SCSTs versus GCTs. METHODS: NCDB was queried for patients diagnosed with SCSTs and GCTs between 2004 and 2013. Descriptive statistics were used to compare sociodemographic and clinical characteristics between groups. Univariable and multivariable Cox proportional hazards regression analyses were used to assess associations with ACM. RESULTS: We identified 42,192 patients diagnosed with testicular cancer between 2004 and 2013, with 280 having SCSTs and 41,912 patients having GCTs. Median age for SCSTs and GCTs was 45 (interquartile range [IQR] 34-59) and 34 (IQR 27-43), respectively (p < 0.001). Median follow-up was 39 and 52 months, respectively. Overall, patients with SCSTs had greater risk of ACM compared to those with GCTs (HR 1.69, 95% CI 1.14-2.50). Private insurance, greater education, and fewer comorbidities were associated with reduced risk of ACM (p < 0.05 for all). Among those with stage I disease, tumor type was not associated with ACM on multivariable analysis. Among those with stage II/III disease, patients with SCSTs had increased risk of ACM compared to patients with GCTs (HR 3.29, 95% CI 1.89-5.72). CONCLUSIONS: Patients with advanced SCSTs had worse survival outcomes compared to those with advanced GCTs. These data suggest a need for further investigation to ascertain effective management recommendations for SCSTs.

Stability of a 17-Gene Genomic Prostate Score in Serial Testing of Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: Genomic testing may improve risk stratification in men with prostate cancer managed by active surveillance. We aimed to characterize the stability and usefulness of serial genomic test scores in men undergoing serial biopsies during active surveillance. MATERIALS AND METHODS: We compiled clinical and disease characteristics of men on active surveillance using an institutional Urologic Outcomes Database. We included patients initially diagnosed with Gleason 3 + 3 prostate cancer who elected active surveillance and received 2, 17-gene GPS (Genomic Prostate Score) results. We examined the association of GPS results and Gleason grade reclassification (Gleason 3 + 4 or greater) with definitive treatment using multivariable Cox proportional hazards regression models. RESULTS: We identified 111 men who underwent serial genomic testing. There were 49 grade reclassification events (44%) at a median followup of 64 months. The mean ± SD GPS change between the first and second biopsies was 2.1 ± 10.3. The GPS at first biopsy (per 5 units HR 1.04, 95% CI 1.00-1.07, p=0.03) was associated with an upgrade at second biopsy, although the second GPS was not (HR 1.02, 95% CI 0.99-1.05, p=0.13). The first and second GPSs (HR 1.09, 95% CI 1.04-1.14 and HR 1.09, 95% CI 1.04-1.14, each p <0.01) were associated with active treatment. CONCLUSIONS: The GPS undergoes small changes with time. Absolute GPS results at the first and second biopsies were associated with Gleason upgrading and transition from active surveillance to active treatment.