Cancer In Prostatectomy Specimens Research Articles

En‐face optical coherence tomography for the detection of cancer in prostatectomy specimens: Quantitative analysis in 20 patients

The increase histopathological evaluation of prostatectomy specimens rises the workload on pathologists. Automated histopathology systems, preferably directly on unstained specimens, would accelerate the pathology workflow. In this study, we investigate the potential of quantitative analysis of optical coherence tomography (OCT) to separate benign from malignant prostate tissue automatically. Twenty fixated prostates were cut, from which 54 slices were scanned by OCT. Quantitative OCT metrics (attenuation coefficient, residue, goodness-of-fit) were compared for different tissue types, annotated on the histology slides. To avoid misclassification, the poor-quality slides, and edges of annotations were excluded. Accurate registration of OCT data with histology was achieved in 31 slices. After removing outliers, 56% of the OCT data was compared with histopathology. The quantitative data could not separate malignant from benign tissue. Logistic regression resulted in malignant detection with a sensitivity of 0.80 and a specificity of 0.34. Quantitative OCT analysis should be improved before clinical use.

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.

Evaluating the Distribution of Prostate Cancer in Prostatectomy Specimens to Determine Eligibility for Focal Therapy

The bRFR was 88.7% at 5 years and 80.7% at 8 years. Five patients (18%) underwent biopsy at a median of 4.6 years (range 3.3-8.3 yr) after treatment and 2 had confirmed disease. Salvage therapy for clinical or biochemical failure included hormonal therapy (3) and salvage prostatectomy (1). Two remain on observation without treatment. The actuarial rate of grade 2 maximum late GU and GI toxicity at 5 and 8 years were 27% and 32%, respectively. Maximum late grade 3 GU and GI toxicity were 4% and 11%, respectively. One patient had grade 4 GI and GU toxicity with rectovesical fistula formation. At last follow-up 21 patients (75%) reported RTOG GU-0 and GI-0 toxicity. Persistent Grade 2 GU and GI toxicity were 10.7% and 7.1%, respectively. Most patients improved GU and GI toxicity scores with longer follow up, although one had persistent Grade 3 GU and Grade 4 GI toxicity. One patient developed metastatic disease and 3 died of causes unrelated to prostate cancer. Conclusions: Dose escalated hypofractionated radiation therapy achieved excellent biochemical control for this predominantly intermediate risk group, although a high incidence of treatment related toxicity resulted in early study termination. The PTV margin employed was generous by current standards, and future investigation of this dose-fractionation schedule should include strategies to safely reduce the PTV margin. Author Disclosure: R.Y. Huang: None. D. Vesprini: None. A.J. Bayley: None. R.G. Bristow: None. P. Chung: None. M.K. Gospodarowicz: None. C. Menard: None. M. Milosevic: None. P.R. Warde: None. C. Catton: None.

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples

The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clinical features of prostate cancer have considerably limited the study of prostate CSCs from fresh human tumor samples. We recently reported the isolation of prostate CSCs directly from human tissues by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells are harvested from surgical specimens and mechanically dissociated. A cell suspension is generated and labeled with fluorescently conjugated HLAI and stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated using a flow cytometer. The principal limitation of this protocol is the frequently microscopic and multifocal nature of primary cancer in prostatectomy specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular characterization and functional validation by transplantation in immunodeficient mice.

Revised Gleason Grading System Is a Better Predictor of Indolent Prostate Cancer at the Time of Diagnosis: Retrospective Clinical-Pathological Study on Matched Biopsy and Radical Prostatectomy Specimens

Introduction/BackgroundThe increase of prostate cancer diagnosis after the introduction of prostate-specific antigen (PSA) screening resulted in overtreatment of patients with low risk tumors. The histological Gleason score (GS) revised in 2005 by the International Society of Urological Pathology (ISUP) is currently the most reliable tool to separate aggressive from indolent prostate cancer. Materials and MethodsUsing the new 2005 GS criteria we retrospectively evaluated biopsy and surgical samples of 1344 patients who underwent radical prostatectomy in our institution. According to the new GS criteria we then selected 134 patients who would have been suitable for active surveillance at the time of biopsy (at least 2 positive cores, PSA < 10 ng/mL, GS ≤ 6). We finally assessed the accuracy of the revised GS in biopsy to predict indolent cancer in the prostatectomy specimens. ResultsThe mean GS increased from 6 to 7 after histological revision in biopsy and prostatectomy specimens. Histological revision determined a significant decrease of patients with GS ≤ 6 and an increase of those with GS ≥ 7 (all P < .001). The average of pathologically indolent disease (organ-confined, GS ≤ 6 at surgery, tumor of any volume) significantly decreased after histological revision (P < .001). ConclusionThe revised ISUP 2005 criteria for Gleason grading provided better stratification of GS ≤ 6 prostate cancer and improved the accuracy for the histological diagnosis of indolent prostate cancer in biopsy and radical prostatectomy specimens.

Abstract B41: Urinary EN2 levels predict tumor volume in men undergoing radical prostatectomy for prostate cancer

Abstract Total tumor volume has been proposed as a guide to managing prostate cancer by immediate treatment versus active surveillance. We evaluated the relationship between levels of a recently described prostate cancer biomarker EN2 (Engrailed-2) in urine and cancer volume in men who had undergone radical prostatectomy for prostate cancer. Archived patient samples from the Aarhus Prostate Cancer Project, Denmark, were assessed. Pre-treatment mid stream urines, without preceding prostatic massage, were collected and stored at −80°C. Urinary EN2 levels were measured by a recently published Enzyme-linked Immunosorbent Assay (ELISA). 88 of the whole cohort of 125 men (70%) were positive for EN2 in their urine (&amp;gt;42.5 μ/L); 38/58 (65%) of men where cancer volume data was available. No statistical relationship was found between urinary EN2 levels and serum PSA. PSA levels did not correlate with tumor stage, combined Gleason grade, total prostatic weight or cancer volume. We found a strong statistical relationship between urinary EN2 and prostate cancer volume by linear regression (p=0.0058). Furthermore, higher EN2 levels correlated with tumor stage T1 versus T2 (p=0.0272). Pre-surgical urinary EN2 levels were associated with increasing tumor stage and closely reflected the volume of cancer in prostatectomy specimens. Given the ease of collection (no prostatic massage required) and the simplicity, low cost and robustness of the assay, EN2 may become a useful biomarker in not only identifying which patients have prostate cancer but may also facilitate risk stratification by indicating the burden of tumor volume. Citation Format: Hardev Pandha, Karina Sorensen, Torben Falck Orntoft, Stephen Langley, Soren Hoyer, Michael Borre, Richard Morgan. Urinary EN2 levels predict tumor volume in men undergoing radical prostatectomy for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B41.