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Objectives: To characterize the role of pathology explanation clinics (PECs) in prostate cancer care and determine their impact on patients, urologic oncologists, and quality of care., Methods: Semistructured interviews with 10 patients with newly diagnosed prostate cancer were conducted before and after a PEC pilot and at the 1- and 6-month follow-up visits. Information about participants' cancer knowledge and anxiety were collected quantitatively. Documented pathologist communications and proper review of outside biopsy slides were collected. Semistructured interviews were also completed with participating urologic oncologists following the pilot., Results: Pathology explanation clinics improved participants' understanding of their diagnosis, cognitively and emotionally supporting them first in their urologic oncology visit and later in making an informed treatment decision. Mean knowledge scores were high, and a minority of participants had prostate cancer anxiety. Urologic oncologists noted improved understanding and reduced anxiety among participants, enabling nuanced conversations about prognosis and management during the visit. By ensuring review of outside biopsy slides and communication of clinically significant or unexpected diagnoses, PECs supported high-quality care and patient safety., Conclusions: In this small pilot, PECs positively affected patients with prostate cancer, their clinicians, and the overall care system. Additional studies in larger populations and diverse settings will be useful., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To evaluate patients' and partners' satisfaction with a prostate cancer survivorship program embedded in urologic-oncologic care. As a part of quality improvement activity, we developed a patient and partner-centered, biopsychosocial support program for men and partners coping with the urinary and sexual side-effects of surgical treatment for prostate cancer. The program became a part of usual care for all prostate cancer patients., Methods: Patients who saw both an advanced practice provider and a sex therapist between August 1, 2018 and July 31, 2019 were eligible. Surveys packets were sent to 146 patients with surveys included for partners (N = 292). We used descriptive statistics to characterize participant responses., Results: Responses were received from 88 patients and 70 partners (56% response rate for the group). Patients and partners reported very high or fairly high satisfaction with the rehabilitation activities of the program (86-97% and 90%-100%, respectively); 91% of patients and 84% of partners thought having pre-operative education and post-operative rehabilitation was a good or fairly good idea; 83% of patients and 79% of partners would very much or somewhat recommend the program to a friend who was considering surgical treatment for prostate cancer., Conclusion: Embedding a patient and partner-centered prostate cancer survivorship support program in oncologic care can positively impact patients' and partners' engagement in and satisfaction with post-operative rehabilitation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: We sought to assess the temporary health-related quality of life (health utility) of nonmagnetic resonance imaging-guided transrectal and transperineal prostate biopsy., Materials and Methods: This is a 2-arm, prospectively enrolled, observational, patient-reported outcomes study, performed between June 2019 and November 2020 at a single academic medical center. Inclusion criteria were men undergoing an outpatient ultrasound-guided prostate biopsy (transrectal or transperineal approach, without magnetic resonance imaging guidance). Patients with a history of Gleason 7+ prostate cancer were excluded. Validated survey instruments were utilized to assess baseline (Short Form 12) and testing-related (Testing Morbidities Index [TMI]) health utility states. The primary outcome was the TMI summary testing-related quality-of-life score (summary utility score; scale: 0=death and 1=perfect health). The TMI is comprised of 7 domains, spanning before, during and after testing experiences. Each domain is scored from 1 (no health impact) to 5 (extreme health impact). Testing-related quality-of-life measures were compared with Mann-Whitney U test., Results: Enrollment rates were 80% (60/75; transrectal) and 86% (60/70; transperineal). All patients (120/120) completed the questionnaire. The TMI summary score for transrectal biopsy was not significantly different from transperineal biopsy (0.86, 95% CI 0.84-0.88 vs 0.83, 95% CI 0.81-0.85; p=0.0774). The largest difference in the testing experiences was related to intraprocedural pain (transrectal biopsy: 2.3, 95% CI 2.1-2.4; transperineal biopsy: 2.9, 95% CI 2.6-3.1; p <0.001)., Conclusions: Transperineal and transrectal prostate biopsies have similar effect on temporary health-related quality-of-life. Transient differences relate to intraprocedural pain. These data can inform clinical decision making and future cost-utility models.

Purpose: Unlike many other cancers, measurement of primary prostate tumor size has no defined role in the management of localized prostate cancer. Here, we assess whether prostate tumor size is associated with aggressive tumor biology using biomarkers of genomic risk., Materials and Methods: We abstracted or imputed tumor size from the primary pathology reports of prostate cancers incorporated in The Cancer Genome Atlas. We used transcriptomic data to estimate the Cell Cycle Progression Score (CCPS, Prolaris), the Genomic Classifier Score (GCS, Decipher) and the Genomic Prostate Score (GPS, OncotypeDx), SChLaP1 expression, and copy number alteration percentage (%CNA) as well as hallmark gene set enrichment analysis., Results: Tumor size and gene expression data was available for 267 men. On multivariable regression adjusted for Gleason Grade Group and tumor purity, tumor size was independently associated with the calculated (c)GCS, cGPS, SChLaP1 expression, and %CNA (P< 0.05), but not cCCPS. Gene set enrichment analysis demonstrated that tumors <5 cc, when adjusting for Gleason grade group, were enriched for androgen response genes, while tumors >5 cc were enriched for MYC targets and genes associated with epithelial mesenchymal transition., Conclusions: Prostate tumor size is independently associated with established markers of genomic risk. This study nominates the size of a primary prostate cancer as candidate for inclusion in future novel risk scores seeking to quantify cancer aggressiveness., (Copyright © 2021. Published by Elsevier Inc.)

Glycolysis has been shown to be required for the cell growth and proliferation in several cancer cells. However, prostate cancer cells were accused of using more fatty acid than glucose to meet their bioenergetic demands. The present study was designed to evaluate the involvement of hexokinase and CPT-1 in the cell growth and proliferation of human prostate cancer cell lines, PC3, and LNCaP-FGC-10. Hexokinase and CPT-1 activities were examined in the presence of different concentrations of their inhibitors, lonidamine and etomoxir, to find the concentration of maximum inhibition ([I max]). To assess cell viability and proliferation, dimethylthiazol (MTT) assay was carried out using [I max] for 24, 48, and 72 h on PC3 and LNCaP cells. Apoptosis was determined using annexin-V, caspase-3 activity assay, Hoechst 33258 staining, and evaluation of mitochondrial membrane potential (MMP). Moreover, ATP levels were measured following lonidamine and etomoxir exposure. In addition, to define the impact of exogenous fatty acid on the cell growth and proliferation, CPT-1 activity was evaluated in the presence of palmitate (50 μM). Hexokinase and CPT-1 activities were significantly inhibited by lonidamine [600 μM] and etomoxir [100 μM] in both cell lines. Treatment of the cells with lonidamine [600 μM] resulted in a significant ATP reduction, cell viability and apoptosis, caspase-3 activity elevation, MMP reduction, and appearance of apoptosis-related morphological changes in the cells. In contrast, etomoxir [100 μM] just decreased ATP levels in both cell lines without significant cell death and apoptosis. Compared with glucose (2 g/L), palmitate intensified CPT-1 activity in both cell lines, especially in LNCaP cells. In addition, activity of CPT-1 was higher in LNCaP than PC3 cells. Our results suggest that prostate cancer cells may metabolize glucose as a source of bioenergetic pathways. ATP could also be produced by long-chain fatty acid oxidation. In addition, these data might suggest that LNCaP is more compatible with palmitate.

Background: Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy., Methods: Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model., Results: The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P < .001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P < .01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (<10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD >0.1 ng/mL/cc or abnormal DRE. When PSAD is <0.1 ng/mL/cc, family history or obesity can identify biopsy candidates., Conclusions: A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer., (Copyright © 2011 American Cancer Society.)

Background: Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via intrinsic and extrinsic pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the DU-145, PC3, and LNcap-FGC10 human prostate cancer cells., Methods: To observe cell viability and proliferation, MTT assay, cell counting, and BrdU assay were carried out in DU-145, PC3, and LNcap-FGC10 cells. Apoptosis was assessed with the analysis of cell cycle, Hoechst 33258 staining, propidium iodide and annexin-V staining, reactive oxygen species (ROS) formation, mitochondrial membrane potential (ΔΨM) measurement, caspase-3 activity assay, Bcl-2 and Bax protein expression. Moreover, the expression of adenosine receptors and the effects of adenosine receptor (A(1) , A(2a) , and A(3) ) antagonists were examined., Result: Adenosine significantly reduced cell proliferation in a dose-dependent manner in DU-145, PC3, and LNcap-FGC10 cell lines. Adenosine induced arrest in the cell-cycle progression in G0/G1 phase through Cdk4/cyclinD1-mediated pathway. Adenosine induced apoptosis, which was determined by morphological changes and increased sub-G1 population. Furthermore, increase of ROS, loss of MMP, activation of caspase-3, and down-regulation of Bcl-2 expression was observed. A(1) , A(2a) , A(2b) , and A(3) adenosine receptors mRNA are expressed in the cell lines. Moreover, adenosine-induced apoptosis was inhibited by MRS1220, A(3) adenosine receptor antagonist., Conclusion: Our results suggest that adenosine induced apoptosis in prostate cancer cells via the mitochondrial pathway and is related to the adenosine receptors. These data might suggest that adenosine could be used as an agent for the treatment of prostate cancer., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: A3 adenosine receptor has shown several physiological and pathological activities, including cell proliferation and apoptosis in various cancer cell lines. This study is designed to investigate molecular mechanism and apoptotic pathway of A3 adenosine receptor in DU-145, PC3 and LNcap-FGC10 human prostate cancer cells., Methods: The expression level of A3 adenosine receptor was examined using real-time RT-PCR. cAMP concentration was also measured. MTT viability, cell counting and BrdU incorporation tests were used to study the cell proliferation effect of IB-MECA. Cell cycle analysis, Annexin V-FITC staining, Hoechst 33258 staining, mitochondrial membrane potential (ΔΨM), caspase-3 activity, Bcl-2 and Bax protein expression were used to detect apoptosis., Result: A3 adenosine receptors mRNAs were detected at different levels. IB-MECA inhibited forskolin-stimulated cAMP. IB-MECA at (1 μM) suppressed cell proliferation and induced G1 cell cycle arrest. Indeed, IB-MECA down-regulated the expression of CDK4, cyclin D1 and up-regulated p53 expression. IB-MECA at (10-100 μM) induced apoptosis. The activity of caspase-3 was also increased. Expression of Bcl-2 was decreased in response to IB-MECA, while the expression of Bax protein was increased. The results showed a significant loss of ΔΨM, in a dose-dependent manner., Conclusion: This study introduces a possible mechanism through A3 adenosine receptor activation. IB-MECA inhibited prostate cancer cells proliferation and induced G1 cell cycle arrest through p53, Cdk4/cyclinD1 pathway. Apoptosis determined by characteristic morphological changes and increased in sub-G1 population. Loss of MMP, activation of caspase-3 and down-regulation of Bcl-2 expression indicated mitochondrial signaling pathway that involved in the apoptosis.