Search

Purpose: Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. multiparametric MRI 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 magnetic resonance (MR)-targeted sampling. The findings for dominant Gleason Grade Group (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.

Background and Objective: Active surveillance (AS) of prostate cancer (PCa) involves regular monitoring for disease progression. The aim is to avoid unnecessary treatment while ensuring appropriate and timely treatment for those whose disease progresses. AS has emerged as the standard of care for low-grade (Gleason grade 1, GG 1) PCa. Opponents are concerned that initial undersampling and delay of definitive management for patients with GG 2 disease may lead to adverse outcomes. We sought to determine whether the timing for definitive management of GG 2 PCa, either upfront or after initial AS, affects recurrence outcomes after radical prostatectomy (RP)., Methods: Participants were diagnosed with cT1-2N0/xM0/x, prostate-specific antigen (PSA) <20 ng/ml, and GG 1-2 PCa between 2000 and 2020 and underwent immediate RP for GG 2 or AS followed by delayed RP on upgrading to GG 2. The outcome was recurrence-free survival (RFS) after surgery, with recurrence defined as either biochemical failure (2 PSA measurements ≥0.2 ng/ml) or a second treatment. Multivariable Cox proportional-hazards regression models were used to calculate associations between the timing for definitive RP and the risk of recurrence, adjusted for age at diagnosis, percentage of positive biopsy cores (PPC), PSA density, PSA before RP, year of diagnosis, surgical margins, genomic risk score, and prostate MRI findings., Key Findings: Of the 1259 men who met the inclusion criteria, 979 underwent immediate RP after diagnosis of GG 2, 190 underwent RP within 12 mo of upgrading to GG 2 on AS, and 90 men underwent RP >12 mo after upgrading to GG 2. The 5-yr RFS rates were 81% for the immediate RP group, 80% for the delayed RP ≤12 mo, and 70% for the delayed RP >12 mo group (univariate log-rank p = 0.03). Cox multivariable regression demonstrated no difference in RFS outcomes between immediate RP for GG 2 disease and delayed RP after upgrading on AS. PPC (hazard ratio [HR] per 10% increment 1.08, 95% confidence interval [CI] 1.02-1.15; p = 0.01) and PSA before RP (HR 1.06, 95% CI 1.03-1.09; p < 0.01) were significantly associated with the risk of recurrence., Conclusions and Clinical Implications: PPC and PSA before RP, but not the timing of definitive surgery after upgrade to GG 2, were associated with the risk of PCa recurrence after RP on multivariable analysis. These findings support the safety of AS and delayed definitive therapy for a subset of patients with GG 2 disease., Patient Summary: In a large group of 1259 patients with low-grade prostate cancer, we found that delaying surgical treatment after an initial period of active surveillance resulted in no differences in prostate cancer recurrence. Our results support the safety of active surveillance for low-grade prostate cancer., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The optimal treatment of localized prostate cancer (PCa) remains controversial., Objective: To compare long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (active surveillance [AS]/watchful waiting [WW]) for PCa., Design, Setting, and Participants: This is a cohort study with long-term follow-up from the multicenter, prospective, largely community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Men with biopsy-proven, clinical T1-3aN0M0, localized PCa were consecutively accrued within 6 mo of diagnosis and had clinical risk data and at least 12 mo of follow-up after diagnosis available., Outcome Measurements and Statistical Analysis: PCa risk was assessed, and multivariable analyses were performed to compare PCa-specific mortality (PCSM) and all-cause mortality by primary treatment, with extensive adjustment for age and case mix using the Cancer of the Prostate Risk Assessment (CAPRA) score and a well-validated nomogram., Results and Limitations: Among 11 864 men, 6227 (53%) underwent RP, 1645 (14%) received BT, 1462 (12%) received EBRT, 1510 (13%) received PADT, and 1020 (9%) were managed with AS/WW. At a median of 9.4 yr (interquartile range 5.8-13.7) after treatment, 764 men had died from PCa. After adjusting for CAPRA score, the hazard ratios for PCSM with RP as the reference were 1.57 (95% confidence interval [CI] 1.24-1.98; p < 0.001) for BT, 1.55 (95% CI 1.26-1.91; p < 0.001) for EBRT, 2.36 (95% CI 1.94-2.87; p < 0.001) for PADT, and 1.76 (95% CI 1.30-2.40; p < 0.001) for AS/WW. In models for long-term outcomes, PCSM differences were negligible for low-risk disease and increased progressively with risk. Limitations include the evolution of diagnostic and therapeutic strategies for PCa over time. In this nonrandomized study, the possibility of residual confounding remains salient., Conclusions: In a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, PCSM was lower after local therapy for those with higher-risk disease, and in particular after RP. Confirmation of these results via long-term follow-up of ongoing trials is awaited., Patient Summary: We evaluated different treatment options for localized prostate cancer in a large group of patients who were treated mostly in nonacademic medical centers. Results from nonrandomized trials should be interpret with caution, but even after careful risk adjustment, survival rates for men with higher-risk cancer appeared to be highest for patients whose first treatment was surgery rather than radiotherapy, hormones, or monitoring., (Copyright © 2023. Published by Elsevier B.V.)

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.

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.

Importance: Active surveillance (AS) is now recognized as the preferred management option for most low-risk prostate cancers to minimize risks of overtreatment. Despite increasing use of AS in the US, wide regional variability has been observed, and these regional variations in contemporary practice have not been well described., Objective: To explore variations between county and Surveillance, Epidemiology, and End Results (SEER) regions in AS in the US., Design, Setting, and Participants: A cohort study using the SEER Prostate with Watchful Waiting (WW) database linked to the County Area Health Resource File for detailed county-level demographics and physician distribution data was conducted from January 2010 to December 2015. Analysis was performed in October 2020. A total of 79 825 men with clinically localized, low-risk prostate cancer eligible for AS or WW were included., Exposures: Multiple patient-, county-, and SEER region-level factors, including age, year of diagnosis, county-level densities of urologists, radiation oncologists, primary care physicians, and SEER registry region., Main Outcomes and Measures: Use of AS or WW as the initial reported treatment strategy were noted. Hierarchical mixed-effect logistic regression models were used to evaluate clustered random regional variation on use of AS or WW. Temporal trends by year in proportions of initial treatment type, as well as county-level local variation, were also estimated., Results: Of 79 825 men (mean [SD] age, 62.8 [7.6] years, 11 292 [14.1%] non-Hispanic Black, 7506 [9.4%] Hispanic) with low-risk prostate cancer, the mean annualized percent increase in AS rates from 2010 to 2015 ranged from 6.3% in New Mexico to 81.0% in New Jersey. Differences across SEER regions accounted for 17% of the total variation in AS. Increasing age (51-60 years: odds ratio [OR], 1.33; 95% CI, 1.21-1.46; 61-70 years: OR, 1.86; 95% CI, 1.70-2.04; 71-80 years: OR, 2.26; 95% CI, 2.05-2.50) was associated with greater odds of AS. Hispanic ethnicity (OR, 0.79; 95% CI, 0.74-0.85), T category (OR, 0.79; 95% CI, 0.73-0.84), and Medicaid enrollment (OR, 0.73; 95% CI, 0.66-0.81) were associated with lower odds of AS. Black race, county-level socioeconomic factors (household income, educational level, and city type), and specialist densities were not associated with AS use., Conclusions and Relevance: In this US cohort study based on the SEER-WW database, although the use of AS increased, considerable practice variation appeared to be associated with geographic location, but use of AS was not associated with Black race, specialty professional density, or socioeconomic factors. This small area variation underlies the broader national trends in AS practice and may inform policies aimed at continuing to affect risk-appropriate care for men throughout the US.

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.

Background: Active surveillance (AS)/watchful waiting (WW) strategy for localized prostate cancer (PCa) is increasingly and broadly endorsed as a preferred option for initial treatment of men with very low- and low-risk PCa, but outcomes can be difficult to analyze in traditional, population-based registries. The recently released Surveillance, Epidemiology, and End Results (SEER) Prostate with WW dataset provides an opportunity to understand national patterns and trends in AS/WW, but the data source itself has not been well described., Objective: To provide a comprehensive description of this dataset and investigate possible biases due to missing data., Design, Setting, and Participants: The SEER is a population-based epidemiologic registry in the USA. Newly diagnosed PCa patient data were collected from 18 SEER registries between 2010 and 2015, with inclusion of a new treatment variable for AS/WW. We identified 316 724 patients in the entire cohort and 257 060 men with clinically localized PCa (T1-2N0M0)., Intervention: Various primary treatments for PCa., Outcome Measurements and Statistical Analysis: The degree of missing data for each variable was measured. In order to investigate possible bias due to missing data for cancer characterization, we compared two versions of the data: one that excluded cases with missing data and one dataset generated applying multiple imputations., Results and Limitations: Only 46% of cases had complete data on basic cancer characteristics for risk stratification. The excluded dataset (N=118 821) differed significantly from the multiple imputation dataset (N=257 060) in the distribution of every reported variable (all p<0.001). The dataset does not distinguish WW from AS, which is a limitation., Conclusions: While the SEER Prostate with WW dataset offers a new method to describe treatment trends for men with PCa, including the use of AS/WW, the amount of missing data should not be ignored., Patient Summary: While the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting dataset offers a new method to describe treatment trends for men with prostate cancer, including the use of active surveillance, it has a significant amount of missing data, which can be a source of potential bias if not addressed properly., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: Active surveillance is becoming more widely accepted as an initial management option for carefully selected men with favorable intermediate-risk prostate cancer (PCa). As prospective active surveillance cohorts mature sufficiently to begin evaluating longer-term outcomes, consensus on more precise evidence-based guidelines is needed to identify the patient cohorts who may be safely managed with active surveillance and what the ideal surveillance protocol entails., Recent Findings: Long-term outcomes updates have suggested a trend toward worse 15-year survival outcomes for intermediate-risk patients on active surveillance compared with definitive treatment, but 'intermediate-risk' is a broad category and there is a subset of favorable intermediate-risk patients for whom survival outcomes remain equivalent. Promising updates to current risk stratification include consideration of genomic classifiers, advanced imaging and more nuanced interpretation of biopsy results., Summary: Despite widespread acknowledgement of the pitfalls of overtreatment in clinically localized PCa, utilization of active surveillance in the intermediate-risk population remains marginal, in part due to the absence of easily interpretable consensus recommendations. As more long-term outcomes data become available for this subgroup, the field is now poised to refine the definition of favorable intermediate-risk patients for whom active surveillance is a safe, evidence-based first-line management option.

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.

Purpose of Review: Active surveillance has become the recommended management strategy for most patients with low-risk prostate cancer (PCa), but whether surveillance criteria can be expanded without compromising oncologic outcomes is a matter of debate. Whereas there is essentially uniform consensus that those with low-risk disease can be safely managed with AS, those with intermediate-risk disease, younger men and African-American men are often excluded., Recent Findings: Outcome data for intermediate-risk patients managed by active surveillance demonstrate acceptable oncologic outcomes, but there is also evidence that such patients have higher rates of progression, adverse disease and metastatic disease. Studies evaluating the utility of quantitative Gleason grade, the use of biomarkers and multiparametric MRI are emerging and are likely to refine risk assessment. Literature describing the effects of young age on outcomes is lacking, but early data appear promising. Data on African-American men show varied results that are sometimes contradictory and further investigation is needed to elucidate the impact of race, independent of socioeconomic status., Summary: Patients with intermediate-risk PCa should not be excluded from active surveillance based on any single, borderline criterion; rather, treatment decisions should be based on the full clinical picture, and may be further refined by patient characteristics and adjunctive tools.