Thrombospondin 1 and cathepsin D improve the detection of high-grade prostate cancer and reduce the number of unnecessary prostate biopsies

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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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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FOLLOW-UP PROSTATE BIOPSIES OF PATIENTS WITH DIAGNOSIS OF HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA AND ATYPICAL SMALL ACINAR PROLIFERATION: PREDICTORS FOR PROSTATE CANCER

European Urology Supplements ◽

10.1016/s1569-9056(08)60611-9 ◽

2008 ◽

Vol 7 (3) ◽

pp. 224

Author(s):

F. Ekren ◽

U. Aliyeva ◽

S. Tamsel ◽

R. Altintas ◽

A. Simsir ◽

...

Keyword(s):

Prostate Cancer ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

High Grade ◽

Atypical Small Acinar Proliferation ◽

Prostate Biopsies

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Analytical performance of thrombospondin-1 and cathepsin D immunoassays part of a novel CE-IVD marked test as an aid in the diagnosis of prostate cancer

PLoS ONE ◽

10.1371/journal.pone.0233442 ◽

2020 ◽

Vol 15 (5) ◽

pp. e0233442

Author(s):

Annalisa Macagno ◽

Alcibiade Athanasiou ◽

Anja Wittig ◽

Ramy Huber ◽

Stephan Weber ◽

...

Keyword(s):

Prostate Cancer ◽

Cathepsin D ◽

Analytical Performance ◽

Thrombospondin 1

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Widespread high grade prostatic intraepithelial neoplasia on biopsy predicts the risk of prostate cancer: A 12 months analysis after three consecutive prostate biopsies

Archivio Italiano di Urologia e Andrologia ◽

10.4081/aiua.2013.2.59 ◽

2013 ◽

Vol 85 (2) ◽

pp. 59 ◽

Cited By ~ 4

Author(s):

Cosimo De Nunzio ◽

Simone Albisinni ◽

Antonio Cicione ◽

Mauro Gacci ◽

Costantino Leonardo ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Biopsy ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

Intraepithelial Neoplasia ◽

High Grade ◽

Prostatic Biopsy ◽

The Third ◽

Prostate Biopsies ◽

Logistic Regressions

Purpose: To evaluate the risk of prostate cancer (PCa) on a third prostate biopsy in a group of patients with two consecutive diagnoses of high grade intraepithelial neoplasia (HGPIN). Materials and methods: From November 2004 to December 2007, patients referred to our clinic with a PSA ! 4 ng/ml or an abnormal digital rectal examination (DRE) were scheduled for trans-rectal ultrasound (TRUS) guided 12-core prostate biopsy. Patients with HGPIN underwent a second prostate biopsy, and if the results of such procedure yielded a second diagnosis of HGPIN, we proposed a third 12-core needle biopsy regardless of PSA value. Crude and adjusted logistic regressions were used to assess predictors of PCa on the third biopsy. Results: A total of 650 patients underwent 12 cores transrectal ultrasound prostatic biopsy in the study period. Of 147 (22%) men with a diagnosis of HGPIN, 117 underwent a second prostatic biopsy after six months and 43 a third biopsy after other six months. After the third biopsy, 19 patients (34%) still showed HGPIN, 15 (35%) were diagnosed with PCa and 9 (21%) presented with chronic prostatitis. Widespread HGPIN on a second biopsy was significantly associated with PCa on further biopsy (!2 = 4.04, p = 0.04). Moreover, the presence of widespread HGPIN significantly predicted the risk of PCa on crude and adjusted logistic regressions. Conclusions: Widespread HGPIN on second biopsy is associated with the presence of PCa on a third biopsy. Nonetheless, the relationship between HGPIN and PCa remains complex and further studies are needed to confirm our findings.

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The percentage of high‐grade prostatic adenocarcinoma in prostate biopsies significantly improves on Grade Groups in the prediction of prostate cancer death

Histopathology ◽

10.1111/his.13888 ◽

2019 ◽

Vol 75 (4) ◽

pp. 589-597 ◽

Cited By ~ 2

Author(s):

Daniel M Berney ◽

Luis Beltran ◽

Holly Sandu ◽

Geraldine Soosay ◽

Henrik Møller ◽

...

Keyword(s):

Prostate Cancer ◽

Prostatic Adenocarcinoma ◽

High Grade ◽

Cancer Death ◽

Prostate Biopsies ◽

Prostate Cancer Death ◽

Grade Groups

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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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Intraductal Carcinoma of the Prostate

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2011-0519-ra ◽

2012 ◽

Vol 136 (4) ◽

pp. 418-425 ◽

Cited By ~ 36

Author(s):

Brian Robinson ◽

Cristina Magi-Galluzzi ◽

Ming Zhou

Keyword(s):

Prostate Cancer ◽

Intraepithelial Neoplasia ◽

High Volume ◽

Intraductal Carcinoma ◽

Definitive Treatment ◽

Secretory Cells ◽

High Grade ◽

Carcinoma Of The Prostate ◽

Prostate Biopsies ◽

Genetic Features

Context.—Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity, characterized by an expansile proliferation of secretory cells within prostatic ducts and acini that demonstrate marked architectural and cytologic atypia. Intraductal carcinoma of the prostate is strongly associated with high-grade and high-volume, invasive prostate cancer and a poorer prognosis than cases without IDC-P. Objective.—To review the historic perspectives, pathologic and genetic features, diagnostic criteria and differential diagnoses, and the clinical significance of IDC-P. Data Sources.—Relevant studies indexed in PubMed. Conclusions.—It is critical to recognize IDC-P, especially in prostate biopsies in which the clinical implications of IDC-P are greatest. Morphologic criteria have been proposed to distinguish IDC-P from several other lesions with similar histologic appearance such as high-grade prostatic intraepithelial neoplasia, invasive cribriform prostate cancer, and urothelial carcinoma involving the prostate. Intraductal carcinoma of the prostate is an uncommon finding in prostate biopsies, and it is even rarer as an isolated finding without concomitant prostate cancer in biopsies. However, patients with isolated IDC-P in biopsies are recommended for either definitive treatment or immediate repeat biopsy.

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Impact of PCA3 on the number of repeat prostate biopsies and sensitivity to detect high-grade cancer in the placebo cohort of the REDUCE study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.111 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 111-111

Author(s):

Bertrand Tombal ◽

Gerald L. Andriole ◽

Louis Smets ◽

Herman Stoevelaar

Keyword(s):

Prostate Cancer ◽

Prostate Volume ◽

High Grade ◽

Current Analysis ◽

Pain Anxiety ◽

Prostate Biopsies ◽

Initial Biopsy ◽

Placebo Cohort ◽

Baseline Psa ◽

Expert Recommendations

111 Background: 10-35% of men with a negative initial biopsy (Bx) have prostate cancer (PCa) found on repeat Bx (rBx). Fear of missing significant cancer frequently results in, often negative, rBx. As Bx is associated with pain, anxiety and complications, a better individualization of the decision for rBx to reduce the number of rBx and overdiagnosis of indolent PCa is needed. Recently, we used the RAND Appropriateness Method (RAM) to develop a model for rBx patient selection, based on expert recommendations and including the PROGENSA PCA3 Assay (Tombal B, et al. World J Urol 2011;doi:10.1007/s00345-011-0721-0). PCA3 has been shown to predict the probability that a rBx will be positive and may be indicative of PCa significance (Aubin SMJ, et al. J Urol 2010;184:1947-52). In the current analysis, we tested the expert recommendations model on the placebo cohort of the REDUCE study. Methods: The RAM expert recommendations were applied to the placebo cohort of the REDUCE study in which 1073 men with a baseline PSA 2.5-10 ng/mL and a prior negative Bx had a PCA3 test before the planned 2-year and 4-year rBx2. For each scenario (with and without PCA3), the number of rBx and the number of missed high-grade (Gleason sum ≥ 7) cancers were assessed. Results: Data from 1024 subjects were available for analysis. In the scenario without PCA3 consideration (reflecting the experts’ recommendations using PSA, DRE, number of previous negative Bx, prostate volume and life expectancy), 267 (26%) of study-mandated rBx were considered inappropriate and the number of missed high-grade cancers was 14. The scenario including also PCA3 consideration led to a reduction of the number of rBx (656 or 64%), while the number of missed high-grade cancers was decreased to 8. The diagnostic accuracy was superior in the model with PCA3: sensitivity for high-grade cancer was 85% vs. 75%, specificity 67% vs. 26%, positive predictive value PPV 13% vs. 5%, NPV 99% vs. 95%. Conclusions: Application of RAM expert recommendations for rBx that include the PCA3 Score can reduce the number of rBx for men with an elevated PSA while maintaining the sensitivity to detect high-grade cancer.

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