Urinary TMPRSS2: Use of ERG and PCA3 to predict tumor volume and Gleason grade in an active surveillance cohort—Results from the Canary/EDRN Prostate Active Surveillance Study.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Daniel W. Lin ◽  
Lisa F Newcomb ◽  
Elissa C Brown ◽  
James D Brooks ◽  
Peter Carroll ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Tumor Volume ◽  
Surveillance Study ◽  
Low Grade ◽  
Gleason Grade ◽  
Aggressive Disease ◽  
Negative Biopsy ◽  
Risk Prostate Cancer

2 Background: Active surveillance is an increasing alternative for the management of low risk prostate cancer; however, there is a crucial need for better biomarkers to distinguish men with indolent versus aggressive disease. Both PCA3 and TMRPSS2-ERG (T2-ERG) are biomarkers that show promise in that they may be associated with more aggressive disease. This study examines the correlation of these biomarkers with higher volume or grade cancer in an active surveillance cohort. Methods: Post-DRE urine was collected prospectively as part of the multi-institutional Canary/EDRN Prostate Active Surveillance Study (PASS). PCA3 and T2-ERG levels were analyzed in urine collected from 401 men at study entry. Many of the men had undergone previous biopsies after initial prostate cancer diagnosis, and 20% of the urine specimens were associated with a negative serial biopsy. Biomarker scores were correlated to clinical and pathologic variables, including tumor volume - measured by percent of biopsy core involvement - and Gleason score, using non-parametric and univariate analyses. Results: Both PCA3 and T2-ERG scores were significantly associated with higher volume disease. For negative repeat biopsy, 1-10%, 11-34%, >34% positive cores, median (95% CI) PCA3 scores were 27 (24-31), 26 (22-33), 40 (29-51), 47 (26-90), p = 0.003 [Kruskal Wallis test (KW)], and median T2-ERG scores were 5 (2-8), 9 (4-14), 21 (14-40), 23 (4-115), p < 0.0001 (KW). Both PCA3 and T2-ERG scores were also significantly associated with presence of higher grade disease. For negative biopsy, Gleason 5 - 6, and Gleason >7, the median PCA3 scores were 27 (24-31), 31 (27-35), 48 (31-92), p = 0.02 (KW), and median T2-ERG scores were 5 (2-8), 14 (9-18), 29 (13-78), p = 0.001 (KW). The odds ratio for a positive biopsy versus a negative biopsy (ref) on modeling was 1.37 (1.04-1.81), p = 0.02 for PCA3 and 1.30 (1.12-1.51), p = 0.0006 for T2-ERG. Conclusions: Both PCA3 and T2-ERG appear to stratify risk, for men on active surveillance, of having aggressive cancer as defined by tumor volume or Gleason score and may have clinical applicability in selecting men with low volume/low grade disease for active surveillance.

Adverse Disease Features in Gleason Score 3 + 4 “Favorable Intermediate-Risk” Prostate Cancer: Implications for Active Surveillance

2017 ◽  
Vol 72 (3) ◽  
pp. 442-447 ◽  
Author(s):  
Alessandro Morlacco ◽  
John C. Cheville ◽  
Laureano J. Rangel ◽  
Derek J. Gearman ◽  
R. Jeffrey Karnes
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Intermediate Risk ◽  
Risk Prostate Cancer

scholarly journals Natural history of prostate cancer on active surveillance: stratification by MRI using the PRECISE recommendations in a UK cohort

2020 ◽  
Author(s):  
Francesco Giganti ◽  
Armando Stabile ◽  
Vasilis Stavrinides ◽  
Elizabeth Osinibi ◽  
Adam Retter ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Rank Test ◽  
Gleason Grade ◽  
Clinical Progression ◽  
Radiological Progression ◽  
Grade Group ◽  
Psa Density

Abstract Objectives The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol. Methods A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves. Results Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5 months; interquartile ranges, 53–98). Of all patients, 313/553 (57%) did not show radiological progression on MRI (PRECISE 1–3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression on MRI (PRECISE 4–5), 146/240 (61%) experienced clinical progression (p < 0.0001). Patients with radiological progression on MRI (PRECISE 4-5) showed a trend to an increase in PSA density. Conclusions Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. Key Points • Patients without radiological progression on MRI (PRECISE 1–3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4–5) during AS. • Patients with radiological progression on MRI (PRECISE 4–5) during AS showed a trend to an increase in PSA density.

Multiparametric prostate MRI and MRI/ultrasound fusion biopsy as tools to follow prostate cancer progression for men on active surveillance.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 63-63 ◽  
Author(s):  
Nabeel Shakir ◽  
Annerleim Walton-Diaz ◽  
Soroush Rais-Bahrami ◽  
Baris Turkbey ◽  
Jason Rothwax ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Cancer Progression ◽  
Predictive Value ◽  
Low Risk ◽  
Fusion Biopsy ◽  
Trus Biopsy ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

63 Background: Active surveillance (AS) is an option for patients with low risk prostate cancer (PCa); however, determining disease progression is challenging. At the NCI, multiparametric MRI (MP-MRI) with our biopsy protocol (MR-US fusion-guided plus 12 core extended sextant biopsy) has been used to confirm eligibility for AS. We evaluated the utility of these modalities in monitoring patients on AS. Methods: Patients who underwent MP-MRI of the prostate with biopsy per our protocol between 2007-2012 were reviewed. We selected a subset who met Johns Hopkins criteria for AS (Gleason score≤6, PSA density≤0.15, tumor involvement of ≤2 cores, and ≤50% of any single core) by outside 12−core TRUS biopsy. Patients with Gleason score≤6 confirmed at first NCI biopsy session were followed with annual MP-MRI and biopsy. MRI progression was defined as an increase in MP-MRI suspicion level, lesion diameter, or number of lesions. Pathologic progression was defined as an increase to Gleason score≥7 in either 12-core or MR-fusion biopsy. We determined the association between MRI and pathologic progression. Results: 129 patients met JHU criteria for AS by outside biopsy. Mean age was 61.6 years and mean PSA 5.16ng/mL. 28/129 (21.7%) patients had Gleason score ≥7 at first NCI biopsy session.31 patients had at least two biopsy sessions (mean follow up 18 months, range 12-54 months) of which 9/31 (29%) increased in Gleason score, all to 3+4=7. Fusion biopsy detected more pathologic progression than did standard biopsy (Table). The positive predictive value of MP-MRI for pathologic progression was 50%, while the negative predictive value was 84%. The sensitivity and specificity of MP-MRI for increase in Gleason score was 67% and 73%, respectively. Conclusions: Stable findings on MP-MRI are associated with Gleason score stability in patients with low-risk PCa choosing AS. The majority of patients who had pathologic progression were detected on fusion biopsy, which may suggest that random biopsies are unnecessary in this population. Larger studies are needed to validate these findings. [Table: see text]

Gleason score upgrade among 10,282 men who underwent surgery as initial treatment in 2010: A population-based study.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 72-72
Author(s):  
Hong Zhang ◽  
Edward M. Messing ◽  
Hamza Ahmed ◽  
Yuhchyau Chen
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Specific Antigen ◽  
Low Risk ◽  
Categorical Variables ◽  
Intermediate Risk ◽  
Time Of Surgery ◽  
Significant Difference ◽  
Risk Prostate Cancer

72 Background: Active surveillance is now accepted initial management for men who have localized prostate cancer with low risk of disease progression. Many criteria have been used for patient identification, including Gleason score (GS) obtained from prostate biopsy. Because of concerns of sampling error, some have recommended repeated biopsy before committing to active surveillance. However, there is limited information about the risk of missing high grade disease using the current standard biopsy approach. This study seeks to compare GS difference from biopsy and surgery to provide an estimated rate of GS upgrade. Methods: The Surveillance, Epidemiology, and End Results (SEER) program was used to identify men with American Joint Committee on Cancer stage T1-2cN0M0 prostate cancer diagnosed between January 2010 and December 2010. Patients who underwent prostatectomy were selected for further analysis. Based on prostate-specific antigen (PSA) levels and GS, cases were divided into low (PSA <=10 and GS <=6) and intermediate (10<PSA<=20 or GS=7) risk groups. The rates of GS upgrade were reported for each group. Chi-square tests were used to assess differences in categorical variables (e.g. age and race) between groups of GS upgrade and no change/downgrade. Results: A total of 10,282 men were evaluated, with 9.2% (n=942) having low-risk disease, and 90.8% (n=9340) having intermediate-risk disease. Among men with low-risk prostate cancer, 22.3% (n=210) had GS upgrade and 0.8% (n=8) had GS 8 disease. Among men with intermediate risk disease, 26.2% (n=2446) had GS upgrade and 2.3% (n=214) had GS 8 disease. There was no statistically significant difference in either age or race distribution among men who had GS upgrade versus no change or downgrade at the time of surgery. Conclusions: A substantial number of low- and intermediate-risk prostate cancer patients had GS upgrade at the time of surgery, but few had upgraded to GS 8 high risk disease. These observations suggest that repeat biopsy prior to active surveillance may not be necessary.

scholarly journals Changes in Prostate Cancer Grade on Serial Biopsy in Men Undergoing Active Surveillance

2011 ◽  
Vol 29 (20) ◽  
pp. 2795-2800 ◽  
Author(s):  
Sima P. Porten ◽  
Jared M. Whitson ◽  
Janet E. Cowan ◽  
Matthew R. Cooperberg ◽  
Katsuto Shinohara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Sampling Error ◽  
Survival Rates ◽  
Specific Antigen ◽  
Extended Period ◽  
Low Risk ◽  
Gleason Grade

Purpose Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time. Patients and Methods Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates. Results Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy. Conclusion A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.

Transperineal sector biopsies: Their role in prostate cancer active surveillance.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 228-228
Author(s):  
Lona Vyas
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Active Surveillance ◽  
Definitive Treatment ◽  
Gleason Grade ◽  
Delayed Treatment ◽  
Prostate Biopsies ◽  
Transrectal Biopsy ◽  
Risk Prostate Cancer

228 Background: Many men with low risk prostate cancer on transrectal biopsy appear suitable for active surveillance (AS). Under staging and grading at diagnosis can result in delayed treatment and risk of poorer oncological outcomes. In most AS series about 30% men have active treatment at a median of two years for presumed disease progression/choice but this may represent disease mischaracterised at initial biopsy. So it is essential to accurately stratify patients before surveillance. We have routinely offered transperineal sector prostate biopsies (TPSB), using 24-32 cores, to all patients considering AS. Methods: 350 patients with apparent low to intermediate risk prostate cancer after transrectal prostate biopsy (TRUS Bx) underwent transperineal sector biopsies. Results: Median age 64 yrs (38–84). Median PSA 7.2 ug/l (0.14–58). 190 had Gleason 3+3, 115 had Gleason 3+4 and 45 >3+4 disease. 145 (41%) patients elected for definitive treatment, in 112 because there was an upgrade or higher disease volume compared with the original TRUS Bx. 33 patients chose definitive treatment rather than continued AS. 205 (59%) patients entered our AS programme, in 25 follow up data is incomplete leaving 180 for analysis. 61 have had repeat TPSB within our protocol and at a median follow up at 2 years in 56/61 (92%) the Gleason score and volume of disease was unchanged. Only 5/180, 2.8% have had treatment for disease progression and additionally 4/180 (2.2%) have chosen active intervention over continued surveillance, despite no evidence of progression. Conclusions: TRUS biopsies under-estimate Gleason grade or cancer volume compared with TPSB. In our cohort of AS patients only 2.8%, at a median follow up of two years, have transferred to definitive treatment for disease progression. TPSB provides the best method to exclude higher risk disease from AS programmes.

Multiparametric magnetic resonance imaging of multifocal prostate cancer to reveal intra-prostatic genomic heterogeneity and novel radio-genomic correlates: Results of the Smarter Prostate Interventions and Therapeutics (SPIRIT) study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 20-20
Author(s):  
Glenn Bauman ◽  
Rohann Correa ◽  
Erfan Aref-Eshghi ◽  
Ryan Alfano ◽  
Bekim Sadikovic ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Prostate Cancer ◽  
Magnetic Resonance ◽  
Gleason Score ◽  
Peripheral Zone ◽  
Imaging Biomarker ◽  
Low Grade ◽  
Gleason Grade ◽  
Resonance Imaging ◽  
Multiparametric Magnetic Resonance Imaging

20 Background: Multi-focality and heterogeneity in prostate cancer can confound the selection of appropriate clinical management. Our study aimed to explore radio-genomic correlations using multiparametric magnetic resonance imaging (mpMRI) against a histopathologic reference standard. Methods: Eight men with prostate cancer who underwent mpMRI followed by prostatectomy were selected for this pilot. Whole-mount histopathology was digitized and co-registered to corresponding MRI slices using a validated high-fidelity methodology.(1) Foci, including central/transitional and peripheral zone lesions were identified by a pathologist, and contoured on digitized histopathology specimens and these digitized maps were used to guide macrodissection of the individual foci for genomic copy-number aberration (CNA) analysis. Correlation of radiomics signatures with the histologic findings and genomic analysis was performed. Results: We found a broad range of CNAs revealing inter-patient and intra-prostatic heterogeneity. Recurrently-altered loci ( e.g., 8p21) containing genes of known significance ( e.g., NKX3-1) were observed. Only radiomic features derived from apparent diffusion coefficient (ADC) independently correlated with both Gleason grade (Rho=-0.62, p=0.003) and median CNA burden (Rho=-0.68, p<0.001). While greater CNA burden expectedly correlated with higher grade, intermediate-grade (Gleason score 3+4 or 4+3) lesions appeared more like either high-grade (Gleason scores ≥4+4) or low-grade (Gleason score 3+3) disease when clustered based on CNA and ADC metrics. Conclusions: These findings suggest ADC derived radiomic metrics may be a useful imaging biomarker across both central and peripheral zone lesion and could aid in further characterization of intra-prostatic biologic heterogeneity. These proof-of-principle data reveal novel radio-genomic correlations that could supplement histologic grading and conventional imaging, thus warranting expanded study and validation. 1) Int J Rad Oncol Biol Phys. 2016; 96(1):188-96.

Tumor Volume on Biopsy of Low Risk Prostate Cancer Managed with Active Surveillance

2018 ◽  
Vol 199 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Jeffrey J. Tosoian ◽  
Mufaddal Mamawala ◽  
Hiten D. Patel ◽  
Ridwan Alam ◽  
Jonathan I. Epstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Tumor Volume ◽  
Low Risk ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

OLDER AGE AND TIME TO LAST BIOPSY ARE ASSOCIATED WITH RISE IN GLEASON SCORE FOR MEN ON ACTIVE SURVEILLANCE FOR LOW RISK PROSTATE CANCER

2008 ◽  
Vol 179 (4S) ◽  
pp. 154-154 ◽  
Author(s):  
Marc A Dall'Era ◽  
Badrinath R Konety ◽  
Maxwell V Meng ◽  
Katsuto Shinohara ◽  
Nannette Perez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Older Age ◽  
Low Risk ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

scholarly journals Predicting Low-Risk Prostate Cancer from Transperineal Saturation Biopsies

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Pim J. van Leeuwen ◽  
Amila Siriwardana ◽  
Monique Roobol ◽  
Francis Ting ◽  
Daan Nieboer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Tumour Volume ◽  
Low Risk ◽  
Gleason Grade ◽  
Saturation Biopsy ◽  
Core Length ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer ◽  
Total Tumour Volume

Introduction. To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC).Materials and Methods. Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA <10 ng/mL, Gleason score <8 PC, diagnosed by transperineal template-guided saturation biopsy were included. The performance of five previously described criteria (i.e., criteria 1–5, criterion 1 stringent (Gleason score 6 + ≤5 mm total max core length PC + ≤3 mm max per core length PC) up to criterion 5 less stringent (Gleason score 6-7 with ≤5% Gleason grade 4) was analysed to assess ability of each to predict insignificant disease in RP specimens (defined as Gleason score ≤6 and total tumour volume <2.5 mL, or Gleason score 7 with ≤5% grade 4 and total tumour volume <0.7 mL).Results. 994 men who underwent RP were included. Criterion 4 (Gleason score 6) performed best with area under the curve of receiver operating characteristics 0.792. At decision curve analysis, criterion 4 was deemed clinically the best performing transperineal saturation biopsy-based definition for low-risk PC.Conclusions. Gleason score 6 disease demonstrated a superior trade-off between sensitivity and specificity for clarifying low-risk PC that can guide treatment and be used as reference test in diagnostic studies.

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