Association of chronic baseline prostate inflammation with lower tumor grade in men with prostate cancer on repeat biopsy.

75 Background: We have previously shown that chronic baseline prostate inflammation in an otherwise benign biopsy was associated with lower risk of prostate cancer in repeat prostate biopsies and lower tumor volumes for those who are diagnosed with cancer. In the present study, we evaluated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade at the 2-year repeat prostate biopsy. Methods: Retrospective analysis of 889 men 50-75 years-old with negative baseline prostate biopsy and positive 2-year repeat biopsy for prostate cancer in the REDUCE study. Acute and chronic prostate inflammation (coded as present or absent) and cancer grade were determined by central pathology. The association of inflammation in baseline biopsies with 2-year repeat biopsy cancer grade (low-grade: Gleason scores 2-6 vs. high-grade: Gleason scores 7-10) was evaluated with t test, chi-squared test and logistic regression controlling for age, race, body-mass index (BMI), digital rectal exam (DRE), prostate volume, baseline pre-study PSA and treatment (dutasteride or placebo). Results: Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammations were significantly associated with each other (P < 0.001). Patients with chronic inflammation had significantly larger prostates (P < 0.001). Both types of inflammation were unrelated to race, BMI, PSA or DRE. At 2-year biopsy, a total of 621 (70%) tumors were low-grade and 268 (30%) tumors were high-grade. In both uni- and multivariable analyses, men with baseline chronic inflammation had significantly less high-grade tumors (univariable OR = 0.64, 95% CI = 0.47-0.87, P = 0.004; multivariable OR = 0.68, 95% CI = 0.50-0.93, P = 0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade. Conclusions: Among men undergoing repeat prostate biopsy 2 years after a negative baseline biopsy who all had cancer on the follow-up biopsy, the presence baseline chronic inflammation was associated with lower prostate cancer grade.

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Atypical Small Acinar Proliferation: Repeat Biopsy and Detection of High Grade Prostate Cancer

Prostate Cancer ◽

10.1155/2015/810159 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Andrew Leone ◽

Katherine Rotker ◽

Christi Butler ◽

Anthony Mega ◽

Jianhong Li ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Prostate Biopsy ◽

Repeat Biopsy ◽

Gleason Grade ◽

High Grade ◽

Atypical Small Acinar Proliferation ◽

Prostate Biopsies ◽

Significant Difference ◽

Initial Biopsy

Purpose. Atypical small acinar proliferation (ASAP) is diagnosed in 1-2% of prostate biopsies. 30–40% of patients with ASAP may be diagnosed with prostate cancer (PCa) on repeat biopsy. Our objective was to examine the association between ASAP and subsequent diagnosis of intermediate/high risk PCa.Materials and Methods. Ninety-six patients who underwent prostate biopsy from 2000 to 2013 and were diagnosed with ASAP were identified. Clinicopathologic features were analyzed. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology.Results. 56/96 (58%) patients had a repeat biopsy. 22/56 (39%) were subsequently diagnosed with PCa. There was no significant difference in patients’ characteristics. Presence of HGPIN on initial biopsy was associated with a benign repeat biopsy (68% versus 23%). 17/22 (77%) had Gleason grade (GG) 3+3 disease and only 5/22 (23%) had GG 3+4 disease.Conclusions. 22/56 patients (39%) of patients who underwent a subsequent prostate biopsy following a diagnosis of ASAP were found to have PCa. 77% of these men were diagnosed with GG 3+3 PCa. Only 23% were found to have intermediate risk PCa and no high risk PCa was identified. Immediate repeat prostate biopsy in patients diagnosed with ASAP may be safely delayed. A multi-institutional cohort is being analyzed.

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A urine-based Exosomal gene expression test stratifies risk of high-grade prostate Cancer in men with prior negative prostate biopsy undergoing repeat biopsy

BMC Urology ◽

10.1186/s12894-020-00712-4 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

James McKiernan ◽

Mikkel Noerholm ◽

Vasisht Tadigotla ◽

Sonia Kumar ◽

Phillipp Torkler ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Prostate Biopsy ◽

Repeat Biopsy ◽

High Grade ◽

Negative Prostate Biopsy

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Is histological prostate inflammation in an initial prostate biopsy a predictor of prostate cancer on repeat biopsy?

International Urology and Nephrology ◽

10.1007/s11255-015-1029-6 ◽

2015 ◽

Vol 47 (8) ◽

pp. 1251-1257 ◽

Cited By ~ 7

Author(s):

Bu Hyeon Yun ◽

Eu Chang Hwang ◽

Ho Song Yu ◽

Hoseok Chung ◽

Sun-Ouck Kim ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Biopsy ◽

Repeat Biopsy ◽

Prostate Inflammation

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Chronic Baseline Prostate Inflammation is Associated with Lower Tumor Grade in Men with Prostate Cancer on Repeat Biopsy: Results from the REDUCE Study

The Journal of Urology ◽

10.1097/ju.0000000000001407 ◽

2020 ◽

Author(s):

Ushasi Naha ◽

J. Curtis Nickel ◽

Gerald L. Andriole ◽

Stephen J. Freedland ◽

Daniel M. Moreira

Keyword(s):

Prostate Cancer ◽

Tumor Grade ◽

Repeat Biopsy ◽

Prostate Inflammation

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A preliminary study of micro-RNAs as minimally invasive biomarkers for the diagnosis of prostate cancer patients

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01875-0 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Simona Giglio ◽

Cosimo De Nunzio ◽

Roberto Cirombella ◽

Antonella Stoppacciaro ◽

Omar Faruq ◽

...

Keyword(s):

Prostate Cancer ◽

Minimally Invasive ◽

Cancer Patients ◽

Strong Predictor ◽

Diagnostic Model ◽

Low Grade ◽

High Grade ◽

Grade Group ◽

Prostate Biopsies ◽

Micro Rnas

Abstract Background A prostate cancer diagnosis is based on biopsy sampling that is an invasive, expensive procedure, and doesn’t accurately represent multifocal disease. Methods To establish a model using plasma miRs to distinguish Prostate cancer patients from non-cancer controls, we enrolled 600 patients histologically diagnosed as having or not prostate cancer at biopsy. Two hundred ninety patients were eligible for the analysis. Samples were randomly divided into discovery and validation cohorts. Results NGS-miR-expression profiling revealed a miRs signature able to distinguish prostate cancer from non-cancer plasma samples. Of 51 miRs selected in the discovery cohort, we successfully validated 5 miRs (4732-3p, 98-5p, let-7a-5p, 26b-5p, and 21-5p) deregulated in prostate cancer samples compared to controls (p ≤ 0.05). Multivariate and ROC analyses show miR-26b-5p as a strong predictor of PCa, with an AUC of 0.89 (CI = 0.83–0.95;p < 0.001). Combining miRs 26b-5p and 98-5p, we developed a model that has the best predictive power in discriminating prostate cancer from non-cancer (AUC = 0.94; CI: 0,835-0,954). To distinguish between low and high-grade prostate cancer, we found that miR-4732-3p levels were significantly higher; instead, miR-26b-5p and miR-98-5p levels were lower in low-grade compared to the high-grade group (p ≤ 0.05). Combining miR-26b-5p and miR-4732-3p we have the highest diagnostic accuracy for high-grade prostate cancer patients, (AUC = 0.80; CI 0,69-0,873). Conclusions Noninvasive diagnostic tests may reduce the number of unnecessary prostate biopsies. The 2-miRs-diagnostic model (miR-26b-5p and miR-98-5p) and the 2-miRs-grade model (miR-26b-5p and miR-4732-3p) are promising minimally invasive tools in prostate cancer clinical management.

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Rate of clinically significant prostate cancer on repeat saturation biopsy after a diagnosis of atypical small acinar proliferation

Urologia Journal ◽

10.1177/0391560321993595 ◽

2021 ◽

pp. 039156032199359

Author(s):

Angelo Totaro ◽

Luca Di Gianfrancesco ◽

Francesco Pinto ◽

Marco Racioppi ◽

Giuseppe Palermo ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Prostate Biopsy ◽

Initial Diagnosis ◽

Repeat Biopsy ◽

Atypical Small Acinar Proliferation ◽

Saturation Biopsy ◽

Prostate Biopsies ◽

History Of ◽

Clinically Significant

Background: Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30%–40% of these patients may develop prostate cancer (PCa) within a 5-year period, often not clinically significant. Current guidelines recommend a repeat biopsy within 3–6 months after the initial diagnosis, but it seem not to be the best strategy. Methods: Objectives—evaluating the natural history of ASAP, stratifying the risk of csPCa after ASAP, identifying predictive factors of PCa after atypical diagnosis. Materials and methods—retrospective single-institutional study on patients undergoing prostate biopsy for suspicious PCa (2005–2016). We evaluated the incidence of overall PCa, intermediate-high risk of PCa and csPCa in case of ASAP, according to D’Amico classification and Epstein modified criteria. Results: Out of 4.567 patients undergoing prostate biopsy, ASAP was detected in 2.6% of cases. All patients with ASAP underwent repeat saturation biopsy within 6 months and PCa was diagnosed in 34.5%. According to D’Amico classification, 26%, 5.9%, and 2.5% had low, intermediate, and high-risk disease, respectively. According modified Epstein criteria, the incidence of csPCa was 12.6%. LRT showed that the overall probability to develop PCa doubled when PSA density (PSAD) moved from values lower than 0.13 ng/ml/cc to class 0.13–0.30 ng/ml/cc, and it tripled when PSAD was higher than 0.30 ng/ml/cc. Conclusions: The rate of csPCa in patients with an initial diagnosis of ASAP who had repeat biopsy was 12.6%. The overall PCa rate was 34.5%. Among patient undergoing RP, an upgrading from ncsPCa to csPCa was reported in 35% of cases. PSAD is the only predictive factor directly associated to the risk of developing PCa on repeat biopsy. These ﬁndings suggest that immediate repeat biopsy remains the correct strategy in absence of novel predictor factors and non-invasive diagnostic evaluations.

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A Urine-Based Exosomal Gene Expression Test Stratifies Risk of High-Grade Prostate Cancer in Men with Prior Negative Prostate Biopsy Undergoing Repeat Biopsy

10.21203/rs.3.rs-26752/v2 ◽

2020 ◽

Author(s):

James McKiernan ◽

Mikkel Noerholm ◽

Vasisht Tadigotla ◽

Sonia Kumar ◽

Phillipp Torkler ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Clinical Features ◽

Prostate Biopsy ◽

Repeat Biopsy ◽

Superior Performance ◽

High Grade ◽

Cut Point ◽

Negative Biopsy ◽

Initial Biopsy

Abstract BACKGROUND: Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate(IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established. Methods: As part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2-10ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results. Results: 229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35% and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.Conclusions: The EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2-10ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.

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