Biopsy Reclassification Research Articles

Association of Baseline Magnetic Resonance Imaging Prostate Imaging Reporting and Data System Score With Prostate Cancer Active Surveillance Early Biopsy Reclassification: Data From the Michigan Urological Surgery Improvement Collaborative (MUSIC).

The purpose of our study was to evaluate the association of baseline MRI Prostate Imaging Reporting and Data System (PI-RADS) score with biopsy reclassification in a multicenter active surveillance (AS) cohort. We identified men in the Michigan Urological Surgery Improvement Collaborative registry (46 hospital-based/academic/private practice urology groups) with National Comprehensive Cancer Network (NCCN) low-risk and favorable intermediate-risk prostate cancer who underwent MRI within 6 months before or after initial biopsy and enrolled in AS from June 2016 to January 2021. The primary objective was to determine the association of baseline MRI PI-RADS score (≥4 lesion) with reclassification to high-grade prostate cancer (≥grade group 3) on surveillance biopsy. Multivariable Cox proportional hazards regression models were constructed and adjusted for pathologic, MRI, and clinical/biopsy factors, with landmark time of 6 months from diagnostic biopsy. We included an interaction term between PI-RADS score and NCCN group in the Cox model. A total of 1491 men were included with median age 64 years (IQR: 59-69) with median follow-up 11.0 months (IQR: 6.0-23.0) after landmark. Baseline PI-RADS ≥ 4 lesion was associated with an increased hazard of biopsy reclassification (HR: 2.3 [95% CI: 1.6-3.2], P < .001), along with grade group 2 vs 1 (HR: 2.5 [95% CI: 1.7-3.7], P < .001), and increasing age (per 10 years; HR: 1.8 [95% CI: 1.4-2.4], P < .001). The interaction between NCCN risk group with MRI findings was not significant (P = .7). In this multicenter cohort study of real-world data, baseline MRI PI-RADS score was significantly associated with early biopsy reclassification in men undergoing AS with NCCN low- or favorable intermediate-risk prostate cancer.

The Journal of Urology® Home Study Course 2023 Volume 209/210.

The Journal of Urology® Home Study Course 2023 Volume 209/210.

Abstract B048: Performance of diagnostic biomarkers in the Canary Prostate cancer Active Surveillance Study (PASS)

Abstract Introduction Many biomarker assays improve sensitivity in diagnosing high grade prostate cancer (PCa), but their performance during active surveillance, after a diagnosis of PCa, is not well understood. Procedures In the multicenter Canary PASS cohort, we explored the contribution of four distinct biomarker panels (blood-based: 4Kpanel, phi; urine-based: PCA3, MDxSelect RNA) and clinical variables in predicting 4-year extreme biopsy reclassification to Gleason Grade Group 3 (GG3) or above. Biomarker assays were performed between 2014-2020 on subcohorts including 727-1,176 participants; outcomes were collected through March 2020. Models were built using a) biomarker, b) biomarker + prostate volume, c) biomarker + biopsy variables d) biomarker + prostate volume + biopsy variables, and, for urine markers e) biomarker + prostate volume + biopsy variables + serum PSA. Clinical PSA was used as a reference. Partly conditional Cox proportional hazards regression models for residual time to event were constructed based on information available at each prediction time, accounting for competing risk. The probability of extreme reclassification within 4 years was calculated after diagnosis and after first follow-up biopsy (Bx1) and the accuracy was assessed with the cross-validated receiver operating characteristic (ROC) curve analysis. Results Cross validated Areas Under the Curve (AUCs) for predictions made with biomarkers ranged from 0.648 (95% CI: 0.581, 0.716) to 0.755 (95% CI: 0.687, 0.824) after diagnosis and from 0.588 (95% CI: 0.480, 0.696) to 0.669 (95% CI: 0.558, 0.780) after Bx1, and were consistently higher than AUCs for clinical PSA at both timepoints; the difference in AUC between biomarker and PSA was statistically significant only for 4Kpanel and phi. Adding clinical variables to predictive models improved AUCs to varying degrees; AUCs for full models with all variables were 0.702 (95% CI: 0.641, 0.764) to 0.776 (95% CI: 0.715, 0.837) after diagnosis and 0.740 (95% CI: 0.656, 0.824) to 0.763 (95% CI: 0.691, 0.836) after Bx1. Adding clinical variables to blood biomarkers resulted in less incremental improvement than for urine markers. A limitation of this study is that prostate MRI was not part of the PASS protocol, although MRI data collected suggests minimal predictive ability during active surveillance. Conclusions Our results suggest that early during prostate cancer active surveillance the blood-based biomarkers of the 4Kpanel and phi may predict future reclassification to higher grade cancer as well as or better than common clinical variables. Clinical variables improve the performance of the urine-based markers of PCA3 or MDxSelect. External validation studies are needed. Citation Format: Lisa F. Newcomb, Yingye Zheng, Menghan Liu, James D. Brooks, Peter R. Carroll, Atreya Dash, William J. Ellis, Christopher J. Filson, Martin E. Gleave, Michael A. Liss, Frances M. Martin, Todd M. Morgan, Peter S. Nelson, Andrew A. Wagner, Daniel W. Lin. Performance of diagnostic biomarkers in the Canary Prostate cancer Active Surveillance Study (PASS) [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B048.

Editorial Comment.

No AccessJournal of UrologyAdult Urology27 Apr 2023Editorial CommentThis article comments on the following:Identifying Men Who Can Remain on Active Surveillance Despite Biopsy Reclassification to Grade Group 2 Prostate Cancer Sandip M. Prasad and Evan Kovac Sandip M. PrasadSandip M. Prasad Garden State Urology, Morristown Medical Center/Atlantic Health System, Morristown, New Jersey More articles by this author and Evan KovacEvan Kovac Rutgers New Jersey Medical School, Cancer Institute of New Jersey, Newark, New Jersey More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003461.01AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, Publish Ahead of Print, pp. – REFERENCES 1. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015; 33(3):272-277. Crossref, Medline, Google Scholar 2. Identifying men who can remain on active surveillance despite biopsy reclassification to Grade Group 2 prostate cancer. J Urol. 2023; 210(1):000-000. Google Scholar 3. Risk of adverse pathology at prostatectomy in the era of MRI and targeted biopsies; rethinking active surveillance for intermediate risk prostate cancer patients. Urol Oncol. 2021; 39(10):729.e1-729.e6. Crossref, Medline, Google Scholar 4. . Optimal use of tumor-based molecular assays for localized prostate cancer. Curr Oncol Rep. 2022; 24(2):249-256. Crossref, Medline, Google Scholar © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology12 Apr 2023Identifying Men Who Can Remain on Active Surveillance Despite Biopsy Reclassification to Grade Group 2 Prostate Cancer Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sandip M. Prasad Garden State Urology, Morristown Medical Center/Atlantic Health System, Morristown, New Jersey More articles by this author Evan Kovac Rutgers New Jersey Medical School, Cancer Institute of New Jersey, Newark, New Jersey More articles by this author Expand All Advertisement PDF downloadLoading ...

Identifying Men Who Can Remain on Active Surveillance Despite Biopsy Reclassification to Grade Group 2 Prostate Cancer.

Men on active surveillance with Grade Group 1 prostate cancer who reclassify to Grade Group 2 on surveillance biopsy often leave active surveillance. We aimed to identify subgroups of men who can safely remain on active surveillance despite preoperative reclassification to Grade Group 2. We studied 249 active surveillance patients with surveillance biopsies classified as Grade Group 1 or Grade Group 2 who underwent radical prostatectomy. Perineural invasion, cancer volume, linear length and maximum percentage of Gleason pattern 4, and prostate-specific antigen density were evaluated. Radical prostatectomy adverse pathology was defined by any of: pN1; ≥pT3; ≥Grade Group 2 with ≥20% Gleason pattern 4; intraductal carcinoma; large cribriform glands. A multivariable logistic regression model incorporating prostate-specific antigen density and perineural invasion stratified radical prostatectomy adverse pathology risk among Grade Group 1 and Grade Group 2 active surveillance patients. 57% (39/68) of Grade Group 1 men reclassified to Grade Group 2 while on active surveillance had favorable radical prostatectomy pathology. Those without biopsy perineural invasion and with low prostate-specific antigen density were more likely to have favorable radical prostatectomy pathology. Most Grade Group 1 men who enter active surveillance and subsequently reclassify to Grade Group 2 have favorable findings at radical prostatectomy and can remain on active surveillance. Among patients reclassified to Grade Group 2, those with low prostate-specific antigen density and without perineural invasion had the lowest risk of radical prostatectomy adverse pathology, comparable to (or below) that of Grade Group 1 patients who were not reclassified to Grade Group 2 preoperatively. Prostate-specific antigen density and perineural invasion stratify risk in active surveillance patients reclassified to Grade Group 2 and, if concordant with other clinicopathological and radiographic findings, can enable more patients to remain on active surveillance. Reclassification to Grade Group 2 alone should not disqualify men from remaining on active surveillance.

Association Between a 22-feature Genomic Classifier and Biopsy Gleason Upgrade During Active Surveillance for Prostate Cancer

BackgroundAlthough the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing the risk of biopsy reclassification for patients on active surveillance, a key event that often triggers treatment. ObjectiveTo evaluate the association between Decipher genomic classifier scores and biopsy Gleason upgrading among patients on active surveillance. Design, setting, and participantsThis was a retrospective cohort study among patients with low- and favorable intermediate-risk prostate cancer on active surveillance who underwent biopsy-based Decipher testing as part of their clinical care. Outcome measurements and statistical analysisWe evaluated the association between the Decipher score and any increase in biopsy Gleason grade group (GG) using univariable and multivariable logistic regression. We compared the area under the receiver operating characteristic curve (AUC) for models comprising baseline clinical variables with or without the Decipher score. Results and limitationsWe identified 133 patients for inclusion with a median age of 67.7 yr and median prostate-specific of 5.6 ng/ml. At enrollment, 75.9% had GG1 and 24.1% had GG2 disease. Forty-three patients experienced biopsy upgrading. On multivariable logistic regression, the Decipher score was significantly associated with biopsy upgrading (odds ratio 1.37 per 0.10 unit increase, 95% confidence interval [CI] 1.05–1.79; p = 0.02). The Decipher score was associated with upgrading among patients with biopsy GG 1 disease, but not GG2 disease. The discriminative ability of a clinical model (AUC 0.63, 95% CI 0.51–0.74) was improved by integration of the Decipher score (AUC 0.69, 95% CI 0.58–0.80). ConclusionsThe Decipher genomic classifier score was associated with short-term biopsy Gleason upgrading among patients on active surveillance. Patient summaryThe results from this study indicate that among patients with prostate cancer undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time. These findings indicate that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance, such as more frequent biopsy for patients with higher scores.

Impact of Early Confirmatory Tests on Upgrading and Conversion to Treatment in Prostate Cancer Patients on Active Surveillance

To assess the impact of confirmatory tests on active surveillance (AS) biopsy disease reclassification and progression to treatment in men with favorable risk prostate cancer (FRPC). We searched the MUSIC registry for men with FRPC managed with AS without or with a confirmatory test. Confirmatory tests included (1) repeat prostate biopsy, (2) genomic tests, (3) prostate magnetic resonance imaging (MRI), or (4) MRI followed by a post-MRI biopsy. Confirmatory test results were deemed reassuring (RA) or nonreassuring (nonRA) according to predefined criteria. Kaplan-Meier curves and multivariable Cox regression models were used to compare surveillance biopsy disease reclassification-free survival and treatment-free survival. Of the 2,514 men with FRPC who were managed on AS, 1211 (48%) men obtained a confirmatory test. We noted differences in the 12-month unadjusted surveillance biopsy disease reclassification-free probability (68%, 83%, and 90%, P < .0001) and 24-month unadjusted treatment-free probability (55%, 81%, and 79%, P < .0001), for men with nonRA confirmatory tests, no confirmatory test, and RA confirmatory tests, respectively. Excluding patients with genomic confirmatory tests, men with RA confirmatory tests were associated with a lower hazard (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.38-0.84, P = .005) and men with nonRA confirmatory tests had an increased hazard (HR 1.97, 95% CI 1.22-3.19, P = .006) of surveillance disease reclassification compared with men without confirmatory tests in the multivariable model. These data suggest men with RA confirmatory tests have less surveillance biopsy reclassification and remain on AS longer than men with nonRA test results. Confirmatory tests may help risk stratify men considering active surveillance.

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

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. 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. 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. 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.

Prostate cancer patients can benefit from 5-alpha-reductase inhibitor treatment: a meta-analysis.

BackgroundThe efficacy and safety of 5α-reductase inhibitors (5ARIs) in treating prostate cancer (PCa) have not been fully determined. We performed a meta-analysis to evaluate the effectiveness and safety of 5ARIs for PCa patients.MethodsA comprehensive literature search of online databases was conducted to obtain comparative studies exploring the effectiveness and safety of 5ARIs in treating PCa up to October 2019. Summarized odds ratio s (OR s) or hazard ratio s (HR s) were calculated to compare the outcomes between 5ARI and control groups. Our meta-analysis was registered in PROSPERO under number CRD42018109809.ResultsA total of 2,277 patients from 10 studies were included. No significant difference was found in prostate-specific antigen progression between two groups (OR = 0.82, 95% CI [0.52–1.29], P = 0.40). However, 5ARI treatment significantly reduced the total progression of PCa (OR = 0.61, 95% CI [0.48–0.77], P < 0.0001), especially for patients with local (OR = 0.56, 95% CI [0.44–0.73], P < 0.00001) and low-Gleason score (≤7) PCa (OR = 0.63, 95% CI [0.48–0.84], P = 0.002). Additionally, 5ARIs also significantly prolonged the progression-free survival time (HR = 0.57, 95% CI [0.34–0.96], P = 0.04) for PCa patients. No significant difference was found in the occurrence of PCa recurrence, metastasis, biopsy reclassification, and side-effects between two groups.ConclusionsOur study suggests that 5ARI treatment can benefit patients with local and low Gleason score (≤7) PCa, especially in delaying the disease progression. More studies with larger sample size and comprehensive study design are still needed to verify our outcomes.

Magnetic Resonance Imaging for the Detection of High Grade Cancer in the Canary Prostate Active Surveillance Study.

We investigated the ability of prostate magnetic resonance imaging to detect Gleason Grade Group 2 or greater cancer in a standardized, multi-institutional active surveillance cohort. We evaluated men enrolled in Canary Prostate Active Surveillance Study with Gleason Grade Group less than 2 and who underwent biopsy within 12 months of multiparametric magnetic resonance imaging. Our primary outcome was biopsy reclassification to Gleason Grade Group 2 or greater. We evaluated the performance of magnetic resonance imaging PI-RADS® score and clinical factors. Multivariable logistic regression models were fit with magnetic resonance imaging and clinical factors and used to perform receiver operating curve analyses. There were 361 participants with 395 prostate magnetic resonance imaging studies with a median followup of 4.1 (IQR 2.0-7.6) years. Overall 108 (27%) biopsies showed reclassification. Defining positive magnetic resonance imaging as PI-RADS 3-5, the negative predictive value and positive predictive value for detecting Gleason Grade Group 2 or greater cancer was 83% (95% CI 76-90) and 31% (95% CI 26-37), respectively. PI-RADS was significantly associated with reclassification (PI-RADS 5 vs 1 and 2 OR 2.71, 95% CI 1.21-6.17, p=0.016) in a multivariable model but did not improve upon a model with only clinical factors (AUC 0.768 vs 0.762). In 194 fusion biopsies higher grade cancer was found in targeted cores in 21 (11%) instances, while 25 (13%) had higher grade cancer in the systematic cores. This study adds the largest cohort data to the body of literature for magnetic resonance imaging in active surveillance, recommending systematic biopsy in patients with negative magnetic resonance imaging and the inclusion of systematic biopsy in patients with positive magnetic resonance imaging.

Natural history of prostatic lesions on serial multiparametric magnetic resonance imaging.

The natural history of prostatic lesions identified on multiparametric magnetic resonance imaging (mpMRI) is largely unknown. We aimed to describe changes observed over time on serial MRI. All patients with ≥2 MRI studies between 2008 and 2015 at our institution were identified. MRI progression was defined as an increase in Prostate Imaging Reporting and Data System (PI-RADS; version 2) or size of existing lesions, or the appearance of a new lesion PIRADS ≥4. Patients on active surveillance (AS) were analyzed for correlation of MRI progression to biopsy reclassification. A total of 83 patients (54 on AS and 29 for diagnostic purposes) underwent serial MRI, with a mean interval of 1.9 years between scans. At baseline, 115 lesions (66 index, 49 non-index) were identified. Index lesions were more likely than non-index lesions to increase in size ≥2 mm (36.2 vs. 7.3 %; p=0.002). Overall progression was more likely to be seen among the index cohort (34.8 vs. 7.6%; p<0.001). New lesions with PI-RADS ≥4 were seen on second imaging in 13 (16.5%) men, and became the index lesion in 29 cases (34.9%). Eighteen men on AS showed evidence of MRI progression (five with new lesions, 13 with progression of a previous lesion). Biopsy reclassification was present in three men (16.7%) with and seven men without MRI progression (19.4%). Overall changes in size and PI-RADS scores of index lesions on MRI were small. New lesions were common, but usually did not alter management.

MP12-02 EFFECTS OF INITIAL GLEASON GRADE ON OUTCOMES DURING ACTIVE SURVEILLANCE FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I1 Apr 2018MP12-02 EFFECTS OF INITIAL GLEASON GRADE ON OUTCOMES DURING ACTIVE SURVEILLANCE FOR PROSTATE CANCER Selma Masic, Janet Cowan, Hao Nguyen, Katsuto Shinohara, Matthew Cooperberg, and Peter Carroll Selma MasicSelma Masic More articles by this author , Janet CowanJanet Cowan More articles by this author , Hao NguyenHao Nguyen More articles by this author , Katsuto ShinoharaKatsuto Shinohara More articles by this author , Matthew CooperbergMatthew Cooperberg More articles by this author , and Peter CarrollPeter Carroll More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.389AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Whether men with GS 3+4 disease are appropriate active surveillance (AS) candidates remains a matter of debate. We evaluated the effects of the initial Gleason grade on biopsy reclassification, treatment and outcomes after radical prostatectomy (RP). METHODS We followed men on AS between 1990 and 2016. Those diagnosed with Gleason 3+3 or 3+4 were included. Outcomes were biopsy reclassification (increase in Gleason grade =3+4 for those starting with Gleason 3+3 or = 4+3 for those with Gleason 3+4, or volume >33% positive cores), treatment, metastasis, adverse pathology (Gleason =4+3 or stage =pT3a or pN1), and prostate specific antigen (PSA) recurrence after deferred RP. Multivariate Cox proportional hazards regression was used to determine risk factors for outcome events. A sensitivity analysis was performed to evaluate outcomes for patients with limited amount of Gleason 3+4. Models were adjusted for age, PSA, PSA density (PSAD), internal versus external diagnostic biopsy, and percentage of cores positive at diagnosis; PSA recurrence-free survival after surgery was also for pathologic stage and positive surgical margins. RESULTS 1,243 men met inclusion criteria with Gleason 3+3 or 3+4 on initial biopsy. A total of 1,119 (90%) had Gleason 3+3 and 124 (10%) 3+4. Patients with Gleason 3+4 had lower reclassification-free survival (17% vs 39%, p<0.01) and treatment-free survival (49% vs 64%, p<0.01) at 5 years. On multivariate analysis, diagnostic grade was not a risk factor for biopsy reclassification (HR 1.21 95% CI 0.94-1.58), but was a risk factor for treatment (HR 1.37 95% CI 1.01-1.85). Among 367 men who underwent deferred RP, patients with Gleason 3+4 had a higher risk of adverse pathology on univariate analysis (HR 1.96 95% CI 1.25-3.08) but not multivariate analysis (HR 1.32 95% CI 0.80-2.18). At three years, patients starting with Gleason 3+4 had lower unadjusted PSA recurrence-free survival (69% vs 91%, p<0.01); the finding was significant on multivariate analysis (HR 3.67 95% CI 1.30-10.36). A sensitivity model showed that grade was associated with risk of PSA recurrence, however, only for patients with more than one high-grade core. Diagnostic grade was not a risk factor for metastasis on univariate or multivariate analyses. CONCLUSIONS Gleason 3+4 at initial biopsy was a risk factor for treatment and PSA recurrence but was not associated with higher risk of biopsy reclassification, metastasis, or adverse pathology. Sensitivity analysis showed that patients with a single core of Gleason 3+4 at diagnosis have outcomes similar to those with Gleason 3+3. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e135 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Selma Masic More articles by this author Janet Cowan More articles by this author Hao Nguyen More articles by this author Katsuto Shinohara More articles by this author Matthew Cooperberg More articles by this author Peter Carroll More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Natural history of prostatic lesions on serial multiparametric magnetic resonance imaging.

The natural history of prostatic lesions identified on multiparametric magnetic resonance imaging (mpMRI) is largely unknown. We aimed to describe changes observed over time on serial MRI. All patients with ≥2 MRI studies between 2008 and 2015 at our institution were identified. MRI progression was defined as an increase in Prostate Imaging Reporting and Data System (PI-RADS; version 2) or size of existing lesions, or the appearance of a new lesion PIRADS ≥4. Patients on active surveillance (AS) were analyzed for correlation of MRI progression to biopsy reclassification. A total of 83 patients (54 on AS and 29 for diagnostic purposes) underwent serial MRI, with a mean interval of 1.9 years between scans. At baseline, 115 lesions (66 index, 49 non-index) were identified. Index lesions were more likely than non-index lesions to increase in size ≥2 mm (36.2 vs. 7.3 %; p=0.002). Overall progression was more likely to be seen among the index cohort (34.8 vs. 7.6%; p<0.001). New lesions with PIRADS ≥4 were seen on second imaging in 13 (16.5%) men, and became the index lesion in 29 cases (34.9%). Eighteen men on AS showed evidence of MRI progression (five with new lesions, 13 with progression of a previous lesion). Biopsy reclassification was present in three men (16.7%) with and seven men without MRI progression (19.4%). Overall changes in size and PIRADS scores of index lesions on MRI were small. New lesions were common, but usually did not alter management.

Refined Analysis of Prostate-specific Antigen Kinetics to Predict Prostate Cancer Active Surveillance Outcomes

BackgroundFor men on active surveillance for prostate cancer, utility of prostate-specific antigen (PSA) kinetics (PSAk) in predicting pathologic reclassification remains controversial. ObjectiveTo develop prediction methods for utilizing serial PSA and evaluate frequency of collection. Design, setting, and participantsData were collected from men enrolled in the multicenter Canary Prostate Active Surveillance Study, for whom PSA data were measured and biopsies performed on prespecified schedules. We developed a PSAk parameter based on a linear mixed-effect model (LMEM) that accounted for serial PSA levels. Outcome measurements and statistical analysisThe association of diagnostic PSA and/or PSAk with time to reclassification (increase in cancer grade and/or volume) was evaluated using multivariable Cox proportional hazards models. Results and limitationsA total of 851 men met the study criteria; 255 (30%) had a reclassification event within 5 yr. Median follow-up was 3.7 yr. After adjusting for prostate size, time since diagnosis, biopsy parameters, and diagnostic PSA, PSAk was a significant predictor of reclassification (hazard ratio for each 0.10 increase in PSAk=1.6 [95% confidence interval 1.2–2.1, p<0.001]). The PSAk model improved stratification of risk prediction for the top and bottom deciles of risk over a model without PSAk. Model performance was essentially identical using PSA data measured every 6 mo to those measured every 3 mo. The major limitation is the reliability of reclassification as an end point, although it drives most treatment decisions. ConclusionsPSAk calculated using an LMEM statistically significantly predicts biopsy reclassification. Models that use repeat PSA measurements outperform a model incorporating only diagnostic PSA. Model performance is similar using PSA assessed every 3 or 6 mo. If validated, these results should inform optimal incorporation of PSA trends into active surveillance protocols and risk calculators. Patient summaryIn this report, we looked at whether repeat prostate-specific antigen (PSA) measurements, or PSA kinetics, improve prediction of biopsy outcomes in men using active surveillance to manage localized prostate cancer. We found that in a large multicenter active surveillance cohort, PSA kinetics improves the prediction of surveillance biopsy outcome.

Eleven-year management of prostate cancer patients on active surveillance: what have we learned?

PurposeTo evaluate the outcomes of active surveillance (AS) on patients with low-risk prostate cancer (PCa) and to identify predictors of disease reclassification.MethodsIn 2005, we defined an institutional AS protocol (Sorveglianza Attiva Istituto Nazionale Tumori [SAINT]), and we joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study in 2007. Eligibility criteria included clinical stage ≤T2a, initial prostate-specific antigen (PSA) <10 ng/mL, and Gleason Pattern Score (GPS) ≤3 + 3 (both protocols); ≤25% positive cores with a maximum core length containing cancer ≤50% (SAINT); and ≤2 positive cores and PSA density <0.2 ng/mL/cm3 (PRIAS). Switching to active treatment was advised for a worsening of GPS, increased positive cores, or PSA doubling time <3 years. Active treatment-free survival (ATFS) was assessed using the ­Kaplan-Meier method. Factors associated with ATFS were evaluated with a multivariate Cox proportional hazards model.ResultsA total of 818 patients were included: 200 in SAINT, 530 in PRIAS, and 88 in personalized AS monitoring. Active treatment-free survival was 50% after a median follow-up of 60 months. A total of 404/818 patients (49.4%) discontinued AS: 274 for biopsy-related reclassification, 121/404 (30%) for off-protocol reasons, 9/404 (2.2%) because of anxiety. Biopsy reclassification was associated with PSA density (hazard ratio [HR] 1.8), maximum percentage of core involvement (HR 1.5), positive cores at diagnostic biopsy (HR 1.6), older age (HR 1.5), and prostate volume (HR 0.6) (all p<0.01). Patients from SAINT were significantly more likely to discontinue AS than were the patients from PRIAS (HR 1.65, p<0.0001).ConclusionsFive years after diagnosis, 50% of patients with early PCa were spared from active treatment. Wide inclusion criteria are associated with lower ATFS. However, at preliminary analysis, this does not seem to affect the probability of unfavorable pathology.

Timing of Adverse Prostate Cancer Reclassification on First Surveillance Biopsy: Results from the Canary Prostate Cancer Active Surveillance Study

During active surveillance for localized prostate cancer, the timing of the first surveillance biopsy varies. We analyzed the Canary PASS (Prostate Cancer Active Surveillance Study) to determine biopsy timing influence on rates of prostate cancer adverse reclassification at the first active surveillance biopsy. Of 1,085 participants in PASS, 421 had fewer than 34% of cores involved with cancer and Gleason sum 6 or less, and thereafter underwent on-study active surveillance biopsy. Reclassification was defined as an increase in Gleason sum and/or 34% or more of cores with prostate cancer. First active surveillance biopsy reclassification rates were categorized as less than 8, 8 to 13 and greater than 13 months after diagnosis. Multivariable logistic regression determined association between reclassification and first biopsy timing. Of 421 men, 89 (21.1%) experienced reclassification at the first active surveillance biopsy. Median time from prostate cancer diagnosis to first active surveillance biopsy was 11 months (IQR 7.8-13.8). Reclassification rates at less than 8, 8 to 13 and greater than 13 months were 24%, 19% and 22% (p = 0.65). On multivariable analysis, compared to men biopsied at less than 8 months the OR of reclassification at 8 to 13 and greater than 13 months were 0.88 (95% CI 0.5,1.6) and 0.95 (95% CI 0.5,1.9), respectively. Prostate specific antigen density 0.15 or greater (referent less than 0.15, OR 1.9, 95% CI 1.1, 4.1) and body mass index 35 kg/m2 or greater (referent less than 25 kg/m2, OR 2.4, 95% CI 1.1,5.7) were associated with increased odds of reclassification. Timing of the first active surveillance biopsy was not associated with increased adverse reclassification but prostate specific antigen density and body mass index were. In low risk patients on active surveillance, it may be reasonable to perform the first active surveillance biopsy at a later time, reducing the overall cost and morbidity of active surveillance.

MP15-08 IS PSA DENSITY OR PSA (OR NEITHER) USEFUL TO PREDICT BIOPSY RECLASSIFICATION IN ACTIVE SURVEILLANCE PATIENTS?

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II1 Apr 2016MP15-08 IS PSA DENSITY OR PSA (OR NEITHER) USEFUL TO PREDICT BIOPSY RECLASSIFICATION IN ACTIVE SURVEILLANCE PATIENTS? Roghayeh Fazeli, Mufaddal Mamawala, Patricia Landis, Sacha Wolf, H. Ballentine Carter, and Bruce J Trock Roghayeh FazeliRoghayeh Fazeli More articles by this author , Mufaddal MamawalaMufaddal Mamawala More articles by this author , Patricia LandisPatricia Landis More articles by this author , Sacha WolfSacha Wolf More articles by this author , H. Ballentine CarterH. Ballentine Carter More articles by this author , and Bruce J TrockBruce J Trock More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2532AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate specific antigen (PSA) and PSA density (PSAD) are widely used to predict risk of biopsy progression in active surveillance (AS) patients. However, their relative prognostic accuracy has not been evaluated, nor has the incremental improvement they provide over other predictors. We compared the predictive accuracy of PSA and PSAD for biopsy reclassification and upgrading in prostate cancer patients managed by AS. METHODS The AS program at Johns Hopkins includes men with clinical stage T1c, PSAD < 0.15 ng/ml/mm3, biopsy Gleason score (GS) =6, <2 positive biopsy cores, =50% core involvement. Older men with low-risk tumors who did not meet all the criteria also entered due to patient preference. Biopsy reclassification is defined by >2 positive cores, >50% core involvement, or GS >7 (upgrading) at annual surveillance biopsy. Cox proportional hazards models of time to biopsy reclassification and upgrading evaluated PSA (PSA =2.5 vs. <2.5) and PSAD (PSAD =0.09 vs. <0.09), adjusted for age, number of positive cores, maximum core involvement, and year of diagnosis. Sub-analyses evaluated whether the effect of PSAD or PSA varied over time (before 2004 vs. 2004 -2014), or by prostate volume (= 45 mm3 vs. <45 mm3), or age at diagnosis (=65 vs. <65). RESULTS 1160 patients (median age 66) with at least 1 surveillance biopsy entered the AS program from 1995-2014. Median follow-up duration, time to reclassification, and time to upgrading were 4.8, 3.3, and 4.2 years, respectively. On multivariable analysis, risk of biopsy reclassification was associated with both binary PSAD, hazard ratio [HR]=1.35 (95% CI 1.1-1.6), p=0.003; and PSA, HR=1.59 (95% CI 1.17-2.15), p=0.003, as was risk of upgrading: PSAD, HR=1.53 (95% CI 1.14-2.06), p=0.004; and PSA, HR=1.71, (95% CI 1.08-2.71), p=0.023. Particularly strong significant associations for both PSAD and PSA were seen in men older than 65 who had prostate volume <45 mm3 (HR=2.40-3.59). However, adding PSA or PSAD to a base model with age, number of positive cores, and maximum tumor percentage gave only small increases in the c-index, except in men with prostate volume <45 (c-index increased from 0.613 to 0.646 for PSA and to 0.648 for PSAD). CONCLUSIONS Both PSAD and PSA have statistically significant predictive value for risks of biopsy reclassification and biopsy upgrading, with neither showing an advantage over the other. However, their utility for risk stratification is particularly important in men older than 65 with prostate volume <45 mm3. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e154-e155 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Roghayeh Fazeli More articles by this author Mufaddal Mamawala More articles by this author Patricia Landis More articles by this author Sacha Wolf More articles by this author H. Ballentine Carter More articles by this author Bruce J Trock More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract 4352: Prediction of prostate cancer progression with biomarkers and tissue morphometry changes

Abstract Introduction: The progression of prostate cancer (PCa) involves both tissue morphometric changes and critical molecular alterations (such as cancer-associated markers). We have studied 80 men that underwent radical prostatectomy (RP) to evaluate this dual approach to discriminate Gleason score and progression. Next, we applied our approach at the diagnostic biopsy of men that chose active surveillance (AS) as an option for the management of their PCa, to predict the likelihood for re-classification of their disease to immediate treatment. Materials &amp; Methods: Two tissue microarrays (TMAs) with 80 RP PCa cases, stratified by Gleason scores were used first. Next, a total of 27 favorable and 24 unfavorable AS biopsy PCa cases were evaluated. In both series we applied multiplex tissue immunoblotting (MTI) &amp; quantitative nuclear morphometry studies. Data were first analyzed alone and then in combination using multivariate logistic regression (MLR) to predict the aggressive RP cases or AS biopsy reclassification status of the cancer. MTI was used to simultaneously detect 5∼6 biomarkers ((-5,-7)ProPSA, PCNA, RBM3, Her2/neu, &amp; CACNA1D, etc) on a single 5 micron section. Proteins on the slide were transferred onto a series of 5∼6 P-film membranes and each membrane was probed with different primary antibody. The quantified FITC fluorescence signal of the biomarker were normalized to CY5 labelled total protein. For the nuclear morphometry analysis, quantification of the nuclear features were achieved either using ImagePro Premier 9.1 Software for the TMAs or the adaptive active contour scheme (AdACM) that uses nuclear shape, architectural and textural features extracted from AS biopsies. RESULTS: Using MLR, to differentiate aggressive PCa (Gleason score 4+3 &amp; &amp;gt; = 8) from less aggressive PCa (Gleason score 3+3 &amp; 3+4) on the TMAs of RP cases, our biomarkers model generated an ROC-AUC of 0.8 with accuracy of 71.43%, while morphometry model generate an ROC-AUC of 0.92 with accuracy of 82.50 %. When combined, it improved to an ROC-AUC of 0.96 and accuracy of 87.01%. Additionally, MLR was used for differentiation unfavorable biopsy cases that requires reclassification due to upgraded Gleason score, increased tumor volume, and/or PSA/PSAD during monitoring and need definitive treatment. On the contrary, favorable cases are very low risk (VLR) PCa biopsies that are not reclassified and can continue monitoring. The biomarkers model produced an ROC-AUC of 0.71 with an accuracy of 73.91% while morphometry model produces an ROC-AUC of 0.84 and accuracy of 74.51%. When combined, the new model produces an ROC-AUC of 0.88 and accuracy of 80.43%. CONCLUSIONS: Our method combining tissue morphometry with biomarkers demonstrated its translational clinical relevance since it can predict PCa aggressiveness in men that have undergone RP. Also, this approach predicts AS PCa cases requiring reclassification and immediate treatment at biopsy. Citation Format: Guangjing Zhu, George Lee, Christine Davis, Luciane Tsukamoto Kagohara, Jonathan I. Epstein, Patricia Landis, H. Ballantine Carter, Anant Madabhushi, Robert W. Veltri. Prediction of prostate cancer progression with biomarkers and tissue morphometry changes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4352. doi:10.1158/1538-7445.AM2015-4352

Magnetic resonance imaging on disease reclassification among active surveillance candidates with low-risk prostate cancer: a diagnostic meta-analysis.

Active surveillance (AS) is an increasingly important attempt to avoid overtreatment of patients who harbor clinically insignificant disease while offering curative treatment to those in whom disease is reclassified as higher risk after an observation period and repeat biopsy. We aim to evaluate the diagnostic performance of magnetic resonance imaging (MRI) in predicting upgrading on confirmatory biopsy in men with low-risk prostate cancer (PCa) on AS. We searched the PubMed for pertinent studies up to November 2014. We used standard methods recommended for meta-analyses of diagnostic test evaluations. The analysis was based on a summary receiver operating characteristic (SROC) curve. Meta-regression analysis was used to assess the effects of some confounding factors on the results of the meta-analysis. The potential presence of publication bias was tested using the Deeks' funnel plots. Seven studies provided the diagnostic data on MRI and AS of PCa, comprising 1028 patients. The pooled estimates of MRI on disease reclassification among AS candidates were as follows: sensitivity, 0.69 (95% confidence interval (CI), 0.44-0.86); specificity, 0.78 (95% CI, 0.53-0.91); positive likelihood ratio, 3.1 (95% CI, 1.6-6.0); negative likelihood ratio, 0.40 (95% CI, 0.23-0.70); and diagnostic odds ratio, 8 (95% CI, 4-16). The P-value for heterogeneity was <0.001. We found that the SROC curve is positioned toward the desirable upper left corner of the curve, and the area under the curve was 0.79 (95% CI, 0.76-0.83). For a pretest probability of 0.20, the corresponding positive predictive value (PPV) was 0.44 and the negative predictive value (NPV) was 0.91. MRI may reveal an unrecognized significant lesion in 33.27% of patients, and biopsy of these areas reclassified 14.59% of cases as no longer fulfilling the criteria for AS. In addition, when no suspicious disease progression (66.34%) was identified on MRI, the chance of reclassification on repeat biopsy was extremely low at 6.13%. MRI, especially multiparametric (MP)-MRI, has a moderate diagnostic accuracy as a significant predictor of disease reclassification among AS candidates. The high NPV and specificity for the prediction of biopsy reclassification upon clinical follow-up suggest that negative prostate MRI findings may support a patient remaining under AS. Although the PPV and sensitivity for the prediction were relatively low, the presence of a suspicious lesion >10 mm lesion may suggest an increased risk for disease progression.

Active surveillance for prostate cancer: when to recommend delayed intervention.

There are no agreed upon guidelines for placing patients on active surveillance (AS). Therefore, there are no absolute criteria for taking patients off AS and when to recommend treatment. The criteria used to define progression are currently based on prostate specific antigen (PSA) kinetics, biopsy reclassification, and change in clinical stage. Multiple studies have evaluated predictors of progression such as PSA, PSA density (PSAD), prostate volume, core positivity, and visible lesion on multiparametric magnetic resonance imaging (mpMRI). Furthermore, published nomograms designed to predict indolent prostate cancer do not perform well when used to predict progression. Newer biomarkers have also not performed well to predict progression. These findings highlight that clinical and pathologic variables are not enough to identify patients that will progress while on AS. In the future, with the use of imaging, biomarkers, and gene expression assays, we should be better equipped to diagnose/stage prostate cancer and to distinguish between insignificant and significant disease.