Prostate Cancer In Radical Prostatectomy Specimens Research Articles

Preoperative Serum Prostate-Specific Antigen Levels Vary According to the Topographical Distribution of Prostate Cancer in Prostatectomy Specimens

To evaluate whether the spatial distribution of prostate cancer (PCa) influences the concentration of prostate-specific antigen (PSA). An observational prospective study was performed in 775 consecutive men with preoperative PSA levels ≤20 ng/mL who underwent radical prostatectomy for organ-confined PCa. We evaluated prostate specimens using a cMDX-based map model of the prostate and determined the prostate volume, number of cancer foci, relative tumor volume, Gleason score, zone of origin, localization, and pathologic stage after stratification according to PSA levels categorized into 3 groups: <4 ng/mL, 4-10 ng/mL, and 10.1-20 ng/mL. The distribution of 5254 PCa foci was analyzed after stratification according to PSA levels and visualized on heat maps. A logistic regression analysis was performed to assess the odds ratios of PSA levels for the presence of PCa in 16 regions. PCa with PSA <4 ng/mL was predominantly localized to the apical part and the peripheral zone of the prostate. PCa with a PSA level 10.1-20 ng/mL (16.4% of cases) was observed more frequently in the anterior part and the base of the prostate than PCa with a PSA level <4 or 4-10 ng/mL (6% and 10%, respectively). Preoperative PSA levels vary according to the spatial distribution of PCa in radical prostatectomy specimens. The probability of anterior PCa is increased with higher PSA serum levels. Regions of interest harboring the PCa can be defined according to preoperative PSA and prostate volume. These findings are useful to optimize the focal therapy or to adjust the radiation fields.

PI-03 LATE-BREAKING ABSTRACT: PREOPERATIVE SERUM PROSTATE SPECIFIC ANTIGEN LEVELS VARY ACCORDING TO TOPOGRAPHICAL DISTRIBUTION OF PROSTATE CANCER IN PROSTATECTOMY SPECIMENS

You have accessJournal of UrologyPlenary Session I: Best Abstract and Late Breaking Abstracts1 Apr 2014PI-03 LATE-BREAKING ABSTRACT: PREOPERATIVE SERUM PROSTATE SPECIFIC ANTIGEN LEVELS VARY ACCORDING TO TOPOGRAPHICAL DISTRIBUTION OF PROSTATE CANCER IN PROSTATECTOMY SPECIMENS Okyaz Eminaga, Reemt Hinkelammert, Elke Eltze, Olaf Bettendorf, and Axel Semjonow Okyaz EminagaOkyaz Eminaga More articles by this author , Reemt HinkelammertReemt Hinkelammert More articles by this author , Elke EltzeElke Eltze More articles by this author , Olaf BettendorfOlaf Bettendorf More articles by this author , and Axel SemjonowAxel Semjonow More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2575AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It remains unclear whether the spatial distribution of prostate cancer (PCa) influences the concentration of prostate specific antigen (PSA). We conducted the current study that investigated the association between PSA levels and the spatial distribution of PCa. METHODS An observational prospective study was performed in 775 consecutive men with preoperative PSA levels ≤20 ng/ml who underwent radical prostatectomy (RP) for organ-confined PCa. We evaluated prostate specimens using a cMDX-based map model of the prostate and determined the prostate volume (PVol), number of cancer foci, relative tumour volume (%TuVol), Gleason score (GS), zone of origin, localisation, and pathologic stage after stratification according to PSA levels categorised into three groups: <4 ng/ml, 4–10 ng/ml, and 10.1–20 ng/ml. The distribution of 5,254 PCa foci was analysed after stratification according to PSA levels and visualised on heat maps. The colour gradient of the heat maps was reduced to 6 colours representing the frequency classification of PCa using an image posterisation effect. A logistic regression analysis was performed to assess the odds ratios of PSA levels for the presence of PCa in 16 regions. RESULTS PCa with PSA <4 ng/ml was predominantly localised to the apical part and the peripheral zone of the prostate. PCa with a PSA level 10.1-20 ng/ml was observed more frequently in the anterior part and the base of the prostate than PCa with a PSA level ≤10 ng/ml. CONCLUSIONS Preoperative PSA levels vary according to the spatial distribution of PCa in RP specimens. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e222-e223 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Okyaz Eminaga More articles by this author Reemt Hinkelammert More articles by this author Elke Eltze More articles by this author Olaf Bettendorf More articles by this author Axel Semjonow More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Development of a needle biopsy-based genomic test to improve discrimination of clinically aggressive from indolent prostate cancer.

4560 Background: Standardized, quantitative tools are needed to improve discrimination of clinically aggressive from indolent prostate cancer at diagnosis. We previously identified multiple genes and biological pathways in radical prostatectomy (RP) specimens associated with clinical recurrence and adverse pathology. We evaluated whether measurement of these genes in prostate needle biopsy (Bx) specimens predicts adverse pathology - high grade (GS ≥ 4+3) and/or non-organ-confined disease (pT3) - in a separate study of AUA low-intermed risk pts treated w/ RP. Methods: All AUA low-intermed risk (cT1-T2a, GS 3+3/3+4) pts treated w/ RP &lt;6 mos from Bx at Cleveland Clinic (1999-2007) w/ available Bx tissue and &lt;3 pos cores were evaluated. Expression of 81 prognostic genes identified in previous RP studies and 5 reference genes was quantitated by RT-PCR in 60 µm manually microdissected FPE prostate needle Bx tissue. Association of gene expression w/ adverse pathology was analyzed by logistic regression controlling false discovery rate (FDR) using Storey’s method. Results: RT-PCR was successful for 167 of 171 (98%) pts (92 AUA low, 75 intermed). At RP, 58 pts (35%) had high-grade and/or non-organ confined disease. 58 of 81(72%) genes predicted high grade and/or non-organ-confined disease (FDR&lt;10%), including all stromal response and androgen genes and the majority of cellular organization genes (82%). Proportionately fewer proliferation (40%), stress response (29%), and basal epithelial (25%) genes were associated w/ adverse path. Androgen and cellular organization genes consistently predicted lower risk; stromal response and proliferation genes predicted higher risk; (majority of std odds ratios &gt;1.5, comparable to the prognostic strength of ER in breast cancer). Conclusions: Genes and biological pathways associated w/ clinically aggressive prostate cancer in RP specimens can be reliably measured by RT-PCR from fixed prostate needle biopsies and predict high-grade, non-organ-confined disease. These results support the potential value of a Bx-based assay to inform selection of immediate treatment or active surveillance for pts diagnosed with prostate cancer on needle Bx.

Proliferative Tumor Doubling Times of Prostatic Carcinoma

Prostate cancer (PCa) has a variable biology ranging from latent cancer to extremely aggressive tumors. Proliferative activities of cancers may indicate their biological potential. A flow cytometric assay to calculate maximum proliferative doubling times (T max) of PCa in radical prostatectomy specimens after preoperative in vivo bromodeoxyuridine (BrdU) infusion is presented. Only 4/17 specimens had tumors large enough for flow cytometric analysis. The T max of tumors was similar and ranged from 0.6 to 3.6 months. Tumors had calculated doubling times 2- to 25-fold faster than their matched normal tissue. Variations in labeling index and T max were observed within a tumor as well as between different Gleason grades. The observed PSA doubling times (PSA-DT) ranged from 18.4 to 32.0 months, considerably slower than the corresponding T max of tumors involved. While lack of data for apoptotic rates is a limitation, apparent biological differences between latent versus aggressive PCa may be attributable to variations in apoptotic rates of these tumors rather than their cell proliferative rates.

The role of transrectal saturation biopsy in tumour localization: pathological correlation after retropubic radical prostatectomy and implication for focal ablative therapy

• To evaluate the accuracy of an initial 24-core prostate biopsy scheme (PBx24) in predicting unilateral prostate cancer (PCa) in radical prostatectomy (RP) specimens. • Between 2005 and 2008, 203 consecutive patients underwent PBx24 followed by RP for PCa. The area under the curve (AUC) was used to evaluate the accuracy of unilateral PCa on PBx24 to predict unilateral PCa in RP specimens. • The positive predictive value (PPV) and negative predictive value (NPV) were also calculated. Moreover, in patients with unilateral PCa on biopsy, univariable and multivariable logistic regression analyses tested the relationship between the presence of unilateral PCa in an RP specimen and the variables: age, prostate-specific antigen (PSA), total prostate volume, clinical stage, primary Gleason grade, secondary Gleason grade and the number of positive cores. • PCa cores were unilateral in 115 patients (56.7%) on biopsy. Of those, only 26 (22.6%) had unilateral PCa in the RP specimen (AUC, 72.9%; PPV, 22.6%; NPV, 98.8%). In patients with clinically low-risk tumours, only 17 of 63 (27%) had a unilateral PCa on PBx24 and in the RP specimen (AUC, 59.1%; PPV, 27.0%; NPV, 100.0%). • None of the examined variables was an independent predictor of the presence of unilateral PCa in the RP specimen (all P > 0.05). • Initial PBx24 is not sufficiently accurate to be dependable as a method of predicting tumour laterality in RP specimens. Therefore, the use of PBx24 to guide hemi-ablation therapy of PCa may lead to mistreatment in a considerable proportion of patients. • Moreover, none of the routinely available clinical and pathological characteristics appears to improve the ability of unilateral PCa on biopsy to predict unilateral PCa in the RP specimen.

Percentages of positive cores, cancer length and Gleason grade 4/5 cancer in systematic sextant biopsy are all predictive of adverse pathology and biochemical failure after radical prostatectomy

We investigated whether the quantitative parameters of systematic sextant biopsies were predictive of either adverse pathological findings or disease recurrence after radical prostatectomy (RP). We retrospectively evaluated a total of 117 men with untreated prostate cancer whose needle biopsies were matched with RP specimens. The pretreatment parameters of the serum prostate-specific antigen (PSA), the PSA density, the percentage of positive biopsy cores, the percentage of cancer length and the percentage of Gleason grade 4/5 cancer in the biopsy were determined and compared with the pathological features of prostate cancer in RP specimens. These pretreatment parameters and pathological factors in the RP specimens, including the cancer volume, the percentage of Gleason grade 4/5 cancer, the positive surgical margin and the seminal vesicle invasion were evaluated for their ability to predict the disease recurrence. The percentages of positive biopsy cores, the Gleason grade 4/5 cancer in the biopsy and the cancer length in the biopsy had a weak correlation with the cancer volume in RP specimens (r = 0.373, 0.345, 0.408, respectively). All quantitative biopsy parameters were strongly predictive of the non-organ-confined status, the positive surgical margin and the seminal vesicle invasion in the logistic regression analysis. The percentage of positive biopsy cores and the percentage of Gleason grade 4/5 cancer in the biopsy predicted biochemical failure after RP. These results indicate that quantitative biopsy parameters are independent predictors of the adverse pathology of prostate cancers and disease recurrence after RP.

Heterogeneity of prostate cancer inradical prostatectomy specimens

Objective To understand the morphologic and spatial relationships of thevarious grades of prostate cancer, we investigated whether poorly differentiated cancer usually arises within the center of a large, well-differentiated tumor or more often forms the periphery or leading edge of the tumor. Methods In a series of one hundred and one completely sectioned whole-mount radical prostatectomy specimens removed from patients with clinical Stage T2 prostate cancer, we mapped the distribution of each of the five Gleason grades and assessed their frequency, proportion, and spatial distribution. Results The average number of different grades present in our patients was 2.7(range 1–5). Over 50 percent of the prostates contained at least three different grades of cancer. The number of different Gleason grades present increased significantly with increasing tumor volume (p < 0.0001). Only 10 percent of the index cancers (largest tumor present) were composed of a single grade and these cancers were small (0.02–1.7 cm 3). Among cancers with multiple grades, the most common finding (53%) was a highgrade cancer present within the core of a larger, more well-differentiated tumor; however, the opposite pattern, low-grade cancer present within a larger poorly differentiated cancer, was also common (30%) and predominated in very large cancers (> 10 cm 3). Conclusion Small prostate cancers are often composed of a single grade, usually Gleason grade 2 or 3. But most palpable cancers contain multiple grades which are arranged in heterogeneous and unpredictable geographic interrelationships.