418: Association between the Dihydrotestosterone Level in the Prostate and Prostate Cancer Aggressiveness Using the Gleason Score

47 Background: New prognostic markers for prostate cancer play an important role in addressing the controversies of over diagnosis and treatment. The cell cycle progression score (CCP) (Prolaris, Myriad Genetic Laboratories, Inc.) is a new RNA-based marker, which improved the prediction of prostate cancer aggressiveness in eight separate cohorts. Each one-unit increase in CCP score corresponds with approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In this analysis, we characterized the CCP score distribution from our initial CCP signature commercial testing. Methods: Our current laboratory database was evaluated for patients whose biopsy was analyzed with the CCP test and whose clinicopathologic data was collected by the ordering physician. Formalin fixed, prostate biopsy tissue from 1,648 patients diagnosed with adenocarcinoma ordered by more than 300 physicians were analyzed. The CCP score was calculated by measuring the RNA expression of 31 cell cycle progression genes normalized to 15 housekeeping genes. Results: Of the 1,648 samples that contained sufficient carcinoma (more than 0.5mm linear extent), 1,604 (97.3%) provided quality RNA for analysis. This retrospective analysis showed a normal distribution for the CCP score ranging from −2.9 to 3.1. Correlation with Gleason score was r=0.35. A relative classification of cancer aggressiveness based on CCP of approximately1,200 patients from multiple cohorts was developed to interpret how the patient’s CCP score compared to that of patients within the same AUA risk category. The thresholds between each of the five intervals are one unit of CCP score apart, with the "consistent" interval centered at the median CCP score. Based on the CCP score, 27.9% of men had a less aggressive cancer compared to the clinicopathologic prediction and were assigned to a lower risk group while 27.6% of patients had a more aggressive cancer. Conclusions: The CCP signature test is a novel assay that can improve risk stratification for men with prostate adenocarcinoma independent of the Gleason score and prostate-specific antigen level. Over 50% of men initially tested in the commercial assay were assigned to a different risk category than predicted by clinicopathologic features alone.

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Prediction of Prostate Cancer Disease Aggressiveness Using Bi-Parametric Mri Radiomics

Cancers ◽

10.3390/cancers13236065 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6065

Author(s):

Ana Rodrigues ◽

João Santinha ◽

Bernardo Galvão ◽

Celso Matos ◽

Francisco M. Couto ◽

...

Keyword(s):

Prostate Cancer ◽

Machine Learning ◽

Gleason Score ◽

Feature Selection Method ◽

Supervised Machine Learning ◽

Lesion Volume ◽

Clinical Images ◽

Gland Volume ◽

Volume Of Interest ◽

Cancer Aggressiveness

Prostate cancer is one of the most prevalent cancers in the male population. Its diagnosis and classification rely on unspecific measures such as PSA levels and DRE, followed by biopsy, where an aggressiveness level is assigned in the form of Gleason Score. Efforts have been made in the past to use radiomics coupled with machine learning to predict prostate cancer aggressiveness from clinical images, showing promising results. Thus, the main goal of this work was to develop supervised machine learning models exploiting radiomic features extracted from bpMRI examinations, to predict biological aggressiveness; 288 classifiers were developed, corresponding to different combinations of pipeline aspects, namely, type of input data, sampling strategy, feature selection method and machine learning algorithm. On a cohort of 281 lesions from 183 patients, it was found that (1) radiomic features extracted from the lesion volume of interest were less stable to segmentation than the equivalent extraction from the whole gland volume of interest; and (2) radiomic features extracted from the whole gland volume of interest produced higher performance and less overfitted classifiers than radiomic features extracted from the lesions volumes of interest. This result suggests that the areas surrounding the tumour lesions offer relevant information regarding the Gleason Score that is ultimately attributed to that lesion.

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Preoperative Prostate Health Index predicts adverse pathology and Gleason score upgrading after radical prostatectomy for prostate cancer

10.21203/rs.3.rs-17248/v1 ◽

2020 ◽

Author(s):

Vojtěch Novák ◽

Štěpán Veselý ◽

Hana Lukšanová ◽

Richard Průša ◽

Otakar Čapoun ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Gleason Score ◽

Specific Antigen ◽

Surgical Margin ◽

Positive Surgical Margin ◽

Health Index ◽

Cancer Aggressiveness ◽

Prostate Health Index ◽

Prostate Health

Abstract Background: We aimed to explore the utility of prostate specific antigen (PSA) isoform [-2]proPSA and its derivatives for prediction of pathological outcome after radical prostatectomy (RP).Methods: Preoperative blood samples were prospectively and consecutively analyzed from 472 patients treated with RP for clinically localized prostate cancer at four medical centers. Measured parameters were PSA, free PSA (fPSA), fPSA/PSA ratio, [-2]proPSA (p2PSA), p2PSA/fPSA ratio and Prostate Health Index (PHI) (p2PSA/fPSA)*√PSA]. Logistic regression models were fitted to determine the accuracy of markers for prediction of pathological Gleason score (GS) ≥7, Gleason score upgrading, extracapsular extension of the tumor (pT3) and the presence of positive surgical margin (PSM). Results: Of 472 patients undergoing RP, 339 (72%) were found to have pathologic GS ≥ 7, out of them 178 (53%) experienced an upgrade from their preoperative GS=6. The findings of pT3 and PSM were present in 132 (28%) and 133 (28%) cases, respectively. At univariable analysis of all the preoperative parameters, PHI was the most accurate predictor of pathological GS ≥7, GS upgrading, pT3 disease and the presence of PSM. Adding of PHI into the base multivariable model increased significantly the accuracy for prediction of pathological GS and GS upgrading by 4.4% (p=0.015) and 5.0% (p=0.025), respectively. Conclusion: We found that PHI provides the highest accuracy in predicting prostate cancer aggressiveness and expansion of the tumor detected at final pathology. The ability of PHI to predict the risk of Gleason score upgrade may help to identify potentially high-risk patients among men with biopsy proven insignificant prostate cancer.

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PSA Velocity Is Associated With Gleason Score in Radical Prostatectomy Specimen: Marker for Prostate Cancer Aggressiveness

Urology ◽

10.1016/j.urology.2008.01.082 ◽

2008 ◽

Vol 72 (5) ◽

pp. 1116-1120 ◽

Cited By ~ 20

Author(s):

Stacy Loeb ◽

Douglas E. Sutherland ◽

Anthony V. D'Amico ◽

Kimberly A. Roehl ◽

William J. Catalona

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Gleason Score ◽

Radical Prostatectomy Specimen ◽

Cancer Aggressiveness ◽

Psa Velocity ◽

Prostatectomy Specimen

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The Change in the Dihydrotestosterone Level in the Prostate Before and After Androgen Deprivation Therapy in Connection With Prostate Cancer Aggressiveness Using the Gleason Score

The Journal of Urology ◽

10.1016/j.juro.2007.05.138 ◽

2007 ◽

Vol 178 (4) ◽

pp. 1282-1289 ◽

Cited By ~ 41

Author(s):

Tsutomu Nishiyama ◽

Toshihiko Ikarashi ◽

Yutaka Hashimoto ◽

Koichi Wako ◽

Kota Takahashi

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Gleason Score ◽

Androgen Deprivation ◽

Cancer Aggressiveness ◽

Before And After

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ARRDC4 and UBXN1: Novel Target Genes Correlated with Prostate Cancer Gleason Score

Cancers ◽

10.3390/cancers13205209 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5209

Author(s):

Jong Jin Oh ◽

Jin-Nyoung Ho ◽

Seok-Soo Byun

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Gleason Score ◽

Target Genes ◽

Epithelial Mesenchymal Transition ◽

Tissue Samples ◽

Mesenchymal Transition ◽

Akt Phosphorylation ◽

Cancer Aggressiveness ◽

Novel Target

To investigate potential markers of the prostate cancer (PCa) Gleason score (GS), genetic arrays in 841 PCa patients were conducted followed by functional validation in PCa cell lines. A total of 841 PCa patients who received radical prostatectomy (RP) from November 2003 to July 2019 were enrolled. HumanExome BeadChip 12v1-1 (Illumina, Inc.; San Diego, CA, USA) exomic arrays were performed on RP tissue samples. Unconditional logistic regression was used to calculate odds ratios to generate estimates of the relative risk of pathologic GS (≥8); SNPs with the highest association were selected and validated using PCa cell lines (PC3, LNCaP, 22Rv1 and DU145). Following transfection with target-gene siRNA, assays for cell viability, wound healing, and transwell invasion were performed. Mean age of enrolled subjects was 66.34 years and median PSA was 8.43 ng/mL. After RP, 122 patients (14.5%) had pathological Gleason scores ≥8. The results from genotyping with 242,186 SNPs by exomic array revealed that 4 SNPs (rs200944490, rs117555780, rs34625170, and rs61754877) were significantly associated with high pathological GS (≥8) within cut-off level to p < 10−5. The most highly associated rs200944490 in ARRDC4 (p = 1.39 × 10−6) and rs117555780 in UBXN1 (p = 2.92 × 10−5) were selected for further validation. The knockdown of UBXN1 and ARRDC4 led to significantly reduced cell proliferation and suppressed migration and invasiveness in PCa cell lines. Epithelial mesenchymal transition (EMT) markers were significantly down-regulated in si-ARRDC4 and si-UBXN1-transfected cells. The expression levels of PI3K-phosphorylation and Akt phosphorylation and NF-κB were also suppressed following knockdown of UBXN1 and ARRDC4. The rs200944490 (ARRDC4) and rs117555780 (UBXN1) were identified as candidate markers predictive of PCa Gleason score which is strongly associated with cancer aggressiveness. Additional validation in future studies is warranted.

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Prostate cancer aggressiveness and age: Impact of p53, BCL-2 and microvessel density

Journal of Investigative Medicine ◽

10.1136/jim-2018-000804 ◽

2018 ◽

Vol 66 (8) ◽

pp. 1142-1146 ◽

Cited By ~ 2

Author(s):

Lisa Calvocoressi ◽

Edward Uchio ◽

John Ko ◽

Krishnan Radhakrishnan ◽

Mihaela Aslan ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Markers ◽

Gleason Score ◽

Microvessel Density ◽

Specific Antigen ◽

B Cell Lymphoma ◽

Cancer Aggressiveness ◽

Increased Risk ◽

Prostate Cancer Death ◽

Therapeutic Decision Making

Older men are more likely to have advanced prostate cancer at time of their diagnosis, but whether prostate tumors are inherently (biologically) more aggressive with advancing age is uncertain. To address this gap in knowledge, we analyzed data from veterans (n=971) diagnosed with prostate cancer during 1991–1995. Factors included age, detection of prostate cancer by screening, prostate-specific antigen (PSA) level, anatomic stage, and Gleason score. Information on molecular markers obtained from immunohistochemical staining of prostate tissue, included B cell lymphoma-2 (bcl-2), p53, and microvessel density (MVD), each having a previously documented association with disease progression and increased risk of prostate cancer death. We first examined the bivariate association of demographic, clinical, and molecular factors with age, and found evidence that race, screening status, Gleason score, PSA, bcl-2, p53, and MVD varied across categories of age in this study population. After further characterizing the association between age and Gleason score, we used logistic regression to examine the association between age and molecular markers—accounting for race, screening status, PSA, and Gleason score. Comparing men older than 80 years to those younger than 70 years, adjusted ORs and 95% CIs were 1.89 (0.73 to 4.92), 1.91 (1.05 to 3.46), and 2.00 (1.06 to 3.78), for positive bcl-2, p53, and MVD markers, respectively; no statistically significant associations were found for men 70–79 years old, compared with men younger than 70 years. These novel findings suggest that very elderly men often present with biologically aggressive prostate cancer; the results also have potential implications for therapeutic decision-making.

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Association Between the Dihydrotestosterone Level in the Prostate and Prostate Cancer Aggressiveness Using the Gleason Score

The Journal of Urology ◽

10.1016/j.juro.2006.06.066 ◽

2006 ◽

Vol 176 (4) ◽

pp. 1387-1391 ◽

Cited By ~ 47

Author(s):

Tsutomu Nishiyama ◽

Toshihiko Ikarashi ◽

Yutaka Hashimoto ◽

Kazuya Suzuki ◽

Kota Takahashi

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Cancer Aggressiveness

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Preoperative prostate health index predicts adverse pathology and Gleason score upgrading after radical prostatectomy for prostate cancer

BMC Urology ◽

10.1186/s12894-020-00711-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Vojtech Novak ◽

Stepan Vesely ◽

Hana Luksanová ◽

Richard Prusa ◽

Otakar Capoun ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Gleason Score ◽

Specific Antigen ◽

Receiver Operating Curve ◽

Positive Surgical Margin ◽

Health Index ◽

Cancer Aggressiveness ◽

Prostate Health Index ◽

Prostate Health

Abstract Background We aimed to explore the utility of prostate specific antigen (PSA) isoform [− 2] proPSA and its derivatives for prediction of pathological outcome after radical prostatectomy (RP). Methods Preoperative blood samples were prospectively and consecutivelyanalyzed from 472 patients treated with RP for clinically localized prostate cancerat four medical centers. Measured parameters were PSA, free PSA (fPSA), fPSA/PSA ratio, [− 2] proPSA (p2PSA), p2PSA/fPSA ratio and Prostate Health Index (PHI)(p2PSA/fPSA)*√PSA]. Logistic regression models were fitted to determine the accuracy of markers for prediction of pathological Gleason score (GS) ≥7, Gleason score upgrading, extracapsular extension of the tumor (pT3) and the presence of positive surgical margin (PSM). The accuracy of predictive models was compared using area under the receiver operating curve (AUC). Results Of 472 patients undergoing RP, 339 (72%) were found to have pathologic GS ≥ 7, out of them 178 (53%) experienced an upgrade from their preoperative GS = 6. The findings of pT3 and PSM were present in 132 (28%) and 133 (28%) cases, respectively. At univariable analysis of all the preoperative parameters, PHI was the most accurate predictor of pathological GS ≥7 (OR 1.02, 95% CI 1.01–1.03, p<0.001), GS upgrading (OR 1.02, 95% CI 1.01–1.03, p<0.003), pT3 disease (OR 1.01, 95% CI 1.00–1.02, p<0.007) and the presence of PSM (OR 1.01, 95% CI 1.00–1.02, p<0.002). Adding of PHI into the base multivariable model increased significantly the accuracy for prediction of pathological GS by 4.4% to AUC = 66.6 (p = 0.015) and GS upgrading by 5.0% to AUC = 65.9 (p = 0.025), respectively. Conclusions Preoperative PHI levels may contribute significantly to prediction of prostate cancer aggressiveness and expansion of the tumor detected at final pathology.

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Preoperative Prostate Health Index predicts adverse pathology and Gleason score upgrading after radical prostatectomy for prostate cancer.

10.21203/rs.3.rs-17248/v2 ◽

2020 ◽

Author(s):

Vojtech Novak ◽

Stepan Vesely ◽

Hana Luksanova ◽

Richard Prusa ◽

Otakar Capoun ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Gleason Score ◽

Specific Antigen ◽

Surgical Margin ◽

Positive Surgical Margin ◽

Health Index ◽

Cancer Aggressiveness ◽

Prostate Health Index ◽

Prostate Health

Abstract Background: We aimed to explore the utility of prostate specific antigen (PSA) isoform [-2]proPSA and its derivatives for prediction of pathological outcome after radical prostatectomy (RP).Methods: Preoperative blood samples were prospectively and consecutively analyzed from 472 patients treated with RP for clinically localized prostate cancer at four medical centers. Measured parameters were PSA, free PSA (fPSA), fPSA/PSA ratio, [-2]proPSA (p2PSA), p2PSA/fPSA ratio and Prostate Health Index (PHI) (p2PSA/fPSA)*√PSA]. Logistic regression models were fitted to determine the accuracy of markers for prediction of pathological Gleason score (GS) ≥7, Gleason score upgrading, extracapsular extension of the tumor (pT3) and the presence of positive surgical margin (PSM). Results: Of 472 patients undergoing RP, 339 (72%) were found to have pathologic GS ≥ 7, out of them 178 (53%) experienced an upgrade from their preoperative GS=6. The findings of pT3 and PSM were present in 132 (28%) and 133 (28%) cases, respectively. At univariable analysis of all the preoperative parameters, PHI was the most accurate predictor of pathological GS ≥7, GS upgrading, pT3 disease and the presence of PSM. Adding of PHI into the base multivariable model increased significantly the accuracy for prediction of pathological GS and GS upgrading by 4.4% (p=0.015) and 5.0% (p=0.025), respectively. Conclusion: We found that PHI provides the highest accuracy in predicting prostate cancer aggressiveness and expansion of the tumor detected at final pathology. The ability of PHI to predict the risk of Gleason score upgrade may help to identify potentially high-risk patients among men with biopsy proven insignificant prostate cancer.

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