Histological Diagnosis Of Prostate Cancer Research Articles

A cross-sectional study of ERG expression and the relationship with clinicopathological features of Prostate cancer in Southwestern Uganda

BackgroundProstate cancer is the leading cause of cancer-related death and the second most commonly diagnosed cancer among men in Uganda and most countries in Sub-Saharan Africa (SSA). The TMPRSS2-ERG fusion gene is the most common genetic alteration seen among prostate cancer patients. There are several contradicting reports about the association of ERG protein with poor prognosis, high PSA, and Gleason score. This study determined the prevalence of ERG expression and the relationship with PSA, Gleason score, and Age of prostate cancer patients in Southwestern Uganda.MethodsWe reviewed 130 archived prostate biopsy (needle and TURP) specimens from patients of age ≥ 50 years who had a histological diagnosis of prostate cancer. We obtained their biodata, and preoperative PSA, from the archived records. We did Immunohistochemistry (IHC) to determine the prevalence of ERG expression.ResultsThe mean patient age in our study was 74.64 ± 10.19 years. Pre-operative PSA levels had been done for 79.2% of the participants. Most cancers (58.46%) were of high grade (grade group 3–5). ERG expression prevalence was 75.4% and its expression was independent of age, re-operative PSA, and Gleason score.ConclusionThere is a significantly higher prevalence of ERG expression in our study compared to what is reported in other African-based studies. The expression of the ERG is independent of age, Gleason score, and serum PSA levels. A high proportion of our prostate cancer has high-grade disease at the time of diagnosis.

The role of urology and radiology in prostate biopsy: current trends and future perspectives.

Prostate biopsy is central to the accurate histological diagnosis of prostate cancer. In current practice, the biopsy procedure can be performed using a transrectal or transperineal route with different technologies available for targeting of lesions within the prostate. Historically, the biopsy procedure was performed solely by urologists, but with the advent of image-guided techniques, the involvement of radiologists in prostate biopsy has become more common. Herein, we discuss the pros, cons and future considerations regarding their ongoing role. A narrative review regarding the current evidence was completed. PubMed and Cochrane central register of controlled trials were search until January 2024. All study types were of consideration if published after 2000 and an English language translation was available. There are no published studies that directly compare outcomes of prostate biopsy when performed by a urologist or radiologist. In all published studies regarding the learning curve for prostate biopsy, the procedure was performed by urologists. These studies suggest that the learning curve for prostate biopsy is between 10 and 50 cases to reach proficiency in terms of prostate cancer detection and complications. It is recognised that many urologists are poorly able to accurately interpret multi parametric (mp)-MRI of theprostate. Collaboration between the specialities is of importance with urology offering the advantage of being involved in prior and future care of the patient while radiology has the advantage of being able to expertly interpret preprocedure MRI. There is no evidence to suggest that prostate biopsy should be solely performed by a specific specialty. The most important factor remains knowledge of the relevant anatomy and sufficient volume of cases to develop and maintain skills.

Transrectal vs. transperineal fusion biopsy of the prostate : Time to switch to the perineal technique-comparison of methods and description of the transperineal procedure under local anesthesia

The clinical and histological diagnosis of prostate cancer is acrucial aspect of the routine work of aurologist. The high prevalence of multiresistant microorganisms leads to an increased incidence of sepsis after transrectal prostate biopsy. It requires a switch from the still gold-standard method to the transperineal fusion biopsy procedure after multiparametric prostate magnetic resonance imaging (MRI). This article provides an overview of the most important differences between the two methods and gives adetailed methodological description of transperineal fusion biopsy under local anesthesia.

TALAPRO-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) vs placebo plus ENZA in patients with DDR gene-mutated, metastatic castration-sensitive prostate cancer (mCSPC).

TPS279 Background: TALA is a poly(ADP-ribose) polymerase inhibitor (PARPi) that has shown efficacy in metastatic castration-resistant prostate cancers with alterations in DNA damage response (DDR) genes involved directly or indirectly in homologous recombination repair (HRR). ENZA is an androgen receptor (AR) inhibitor and established therapy for mCSPC. Since PARP activity has been shown to support AR function, PARP inhibition may increase sensitivity to AR-directed therapies. In addition, AR blockade downregulates HRR gene regulation, which has been hypothesized to induce a “ BRCAness” phenotype. These studies suggest that TALA in combination with ENZA may significantly improve clinical outcomes for men with mCSPC and DDR-HRR alterations. The phase 3, double-blind, randomized trial TALAPRO-3 (NCT04821622) herein presented will compare the combination of TALA plus ENZA vs placebo plus ENZA in this setting. Methods: Approximately 550 patients with mCSPC harboring DDR-HRR alterations will be randomized to TALA (0.5 mg once daily [QD]) plus ENZA (160 mg QD) or placebo (once daily) plus ENZA (160 mg QD). Patients will be stratified according to de novo mCSPC vs relapsed mCSPC, high-volume disease vs low-volume disease, where high-volume disease is defined as the presence of visceral metastases or ≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis, and BRCA vs non-BRCA mutational status. Key eligibility criteria include age ≥18 years; histological diagnosis of prostate cancer; alterations in at least one of 12 DDR/HRR genes known to sensitize patients to PARPi ( ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C); and metastatic disease (no brain metastases). Primary endpoint is radiographic progression-free survival (defined as time to radiographic progression in soft tissue per Response Evaluation Criteria in Solid Tumors version 1.1 or in bone per Prostate Cancer Working Group 3 criteria by investigator, or death). Secondary endpoints include overall survival, safety, and patient-reported outcomes. Patient recruitment is planned/ongoing at approximately 285 sites in 27 countries, including the US and Europe, South America, South Africa, and Asia-Pacific. As of 30 September 2022, a total of 319 patients have been randomized in the study. This study was approved by an Institutional Review Board. Clinical trial information: NCT04821622 .

TALAPRO-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) versus placebo plus ENZA in patients with DDR gene–mutated, metastatic castration-sensitive prostate cancer (mCSPC).

TPS5096 Background: TALA is a poly(ADP-ribose) polymerase inhibitor (PARPi) approved as monotherapy for germline BRCA1/2-mutated HER2-negative advanced breast cancer. Clinical efficacy in metastatic castration-resistant prostate cancers (mCRPC) with alterations in DNA damage response (DDR) genes involved directly or indirectly in homologous recombination repair (HRR) has been demonstrated with some PARPi. Phase 3 study findings (de Bono et al. N Engl J Med, 2020;382:2091-2102) resulted in the approval of olaparib for mCRPC. ENZA is an androgen receptor (AR) inhibitor and established therapy for mCSPC. Since PARP activity has been shown to support AR function, PARP inhibition may increase sensitivity to AR-directed therapies. In addition, AR blockade downregulates HRR gene regulation, which has been hypothesized to induce a “ BRCAness” phenotype. A Phase 2 study of TALA monotherapy (TALAPRO-1) demonstrated robust antitumor activity in men with heavily pretreated, HRR-mutated mCRPC. The Phase 3, double-blind, randomized trial TALAPRO-3 (NCT04821622) herein presented will compare the combination of TALA plus ENZA vs placebo plus ENZA in men with mCSPC with DDR/HRR alterations. Methods: Approximately 550 patients with mCSPC harboring DDR/HRR alterations will be randomized to TALA (0.5 mg once daily) plus ENZA (160 mg once daily) or placebo (once daily) plus ENZA (160 mg once daily). Patients will be stratified according to de novo mCSPC vs relapsed mCSPC, high-volume disease vs low-volume disease, where high-volume disease is defined as the presence of visceral metastases or ≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis and BRCA vs non-BRCA mutational status. Key eligibility criteria include age ≥18 years; histological diagnosis of prostate cancer; alterations in at least one of 12 DDR/HRR genes known to sensitize patients to PARPi ( ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C); and metastatic disease (no brain metastases). Primary endpoint is rPFS (time to radiographic progression in soft tissue per RECIST 1.1 or in bone per PCWG3 criteria by investigator, or death). Secondary endpoints include overall survival, safety, and patient-reported outcomes. Patient recruitment is planned at approximately 285 sites in 27 countries, including the US and Europe, South America, South Africa, and Asia-Pacific. This study was approved by an Institutional Review Board. Clinical trial information: NCT04821622.

Talapro-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) versus placebo plus enza in patients with DDR gene mutated metastatic castration-sensitive prostate cancer (mCSPC).

TPS221 Background: TALA is a poly(ADP-ribose) polymerase inhibitor (PARPi) approved as monotherapy for germline BRCA1/2-mutated HER 2-negative advanced breast cancer. PARPi have demonstrated substantial clinical efficacy in metastatic castration-resistant prostate cancers (mCRPC) with alterations in DNA damage response (DDR) genes involved directly or indirectly in homologous recombination repair (HRR). Phase 3 study findings (de Bono et al. N Engl J Med. 2020;382:2091-2102) resulted in the approval of olaparib for mCRPC. ENZA is an androgen receptor (AR) inhibitor and established therapy for mCSPC. Since PARP activity has been shown to support AR function, PARP inhibition is expected to increase sensitivity to AR-directed therapies. In addition, AR blockade downregulates HRR gene regulation, which has been hypothesized to induce a “ BRCAness ” phenotype . A phase 2 study of TALA monotherapy (TALAPRO-1) demonstrated robust antitumor activity in men with heavily pretreated, HRR-mutated mCRPC . The Phase 3, double-blind, randomized trial TALAPRO-3 (NCT04821622) herein presented will compare the combination of TALA plus ENZA versus placebo plus ENZA in men with mCSPC with DDR/HRR alterations. Methods: Approximately 550 patients with mCSPC harboring DDR/HRR alterations will be randomized to TALA (0.5 mg once daily) plus ENZA (160 mg once daily) or placebo (once daily) plus ENZA (160 mg once daily). Key eligibility criteria include age ≥18 years; histological diagnosis of prostate cancer; alterations in 12 DDR/HRR genes known to sensitize to PARPi ( ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C); and metastatic disease (no brain metastases). Primary endpoint is rPFS (time to radiographic progression in soft tissue per RECIST 1.1 or in bone per PCWG3 criteria by investigator, or death). Secondary endpoints include overall survival, safety, and patient-reported outcomes. Patient recruitment is planned at approximately 285 sites in 27 countries, including the US and Europe, South America, South Africa, and Asia-Pacific. Clinical trial information: NCT04821622.

The molecular mechanisms of fluoroquinolone resistance found in rectal swab isolates of Enterobacterales from men undergoing a transrectal prostate biopsy: the rationale for targeted prophylaxis

BackgroundTransrectal ultrasound-guided prostate biopsy (TRUS-Bx) is considered an essential urological procedure for the histological diagnosis of prostate cancer. It is, however, considered a “contaminated” procedure which may lead to infectious complications. Recent studies suggest a significant share of fluoroquinolone-resistant rectal flora in post-biopsy infections.MethodsThe molecular mechanisms of fluoroquinolone resistance, including PMQR (plasmid-mediated quinolone resistance) as well as mutation in the QRDRs (quinolone-resistance determining regions) of gyrA, gyrB, parC and parE, among Enterobacterales isolated from 32 of 48 men undergoing a prostate biopsy between November 2015 and April 2016 were investigated. Before the TRUS-Bx procedure, all the patients received an oral antibiotic containing fluoroquinolones.ResultsIn total, 41 Enterobacterales isolates were obtained from rectal swabs. The MIC of ciprofloxacin and the presence of common PMQR determinants were investigated in all the isolates. Nine (21.9%) isolates carried PMQR with qnrS as the only PMQR agent detected. DNA sequencing of the QRDRs in 18 Enterobacterales (E. coli n = 17 and E. cloacae n = 1) isolates with ciprofloxacin MIC ≥ 0.25 mg/l were performed. Substitutions in the following codons were found: GyrA—83 [Ser → Leu, Phe] and 87 [Asp → Asn]; GyrB codon—605 [Met → Leu], ParC codons—80 [Ser → Ile, Arg] and 84 [Glu → Gly, Met, Val, Lys], ParE codons—458 [Ser → Ala], 461 [Glu → Ala] and 512 [Ala → Thr]. Six isolates with ciprofloxacin MIC ≥ 2 mg/l had at least one mutation in GyrA together with qnrS.ConclusionsThis study provides information on the common presence of PMQRs among Enterobacterales isolates with ciprofloxacin MIC ≥ 0.25 mg/l, obtained from men undergoing TRUS-Bx. This fact may partially explain why some men develop post-TRUS-Bx infections despite ciprofloxacin prophylaxis.

MP11-10 RE-REFERRAL RATES IN THE MEDIUM TERM IN PATIENTS WITH A NON-SUSPICIOUS MPMRI WITHIN THE RAPID PATHWAY

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-10 RE-REFERRAL RATES IN THE MEDIUM TERM IN PATIENTS WITH A NON-SUSPICIOUS MPMRI WITHIN THE RAPID PATHWAY Mariana Bertoncelli Tanaka, Uma Walter, David Eldred-Evans, Edward J. Bass, Martin J. Connor, Pallab Sarkar, Feargus Hoskings-Jervis, Heather Bhola-Stewart, Elizabeth Pegers, Laura Powell, Deepa Leelamany, Kathie Wong, Shahzad Ahmad, Henry Tam, Hasan Qazi, Stephen Gordon, David Hrouda, Stuart McCracken, Mathias Winkler, and Hashim U. Ahmed Mariana Bertoncelli TanakaMariana Bertoncelli Tanaka More articles by this author , Uma WalterUma Walter More articles by this author , David Eldred-EvansDavid Eldred-Evans More articles by this author , Edward J. BassEdward J. Bass More articles by this author , Martin J. ConnorMartin J. Connor More articles by this author , Pallab SarkarPallab Sarkar More articles by this author , Feargus Hoskings-JervisFeargus Hoskings-Jervis More articles by this author , Heather Bhola-StewartHeather Bhola-Stewart More articles by this author , Elizabeth PegersElizabeth Pegers More articles by this author , Laura PowellLaura Powell More articles by this author , Deepa LeelamanyDeepa Leelamany More articles by this author , Kathie WongKathie Wong More articles by this author , Shahzad AhmadShahzad Ahmad More articles by this author , Henry TamHenry Tam More articles by this author , Hasan QaziHasan Qazi More articles by this author , Stephen GordonStephen Gordon More articles by this author , David HroudaDavid Hrouda More articles by this author , Stuart McCrackenStuart McCracken More articles by this author , Mathias WinklerMathias Winkler More articles by this author , and Hashim U. AhmedHashim U. Ahmed More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Our ‘one-stop’ Rapid Access Prostate Imaging and Diagnosis (RAPID) pathway across five hospitals in our region streamlined our one-stop mpMRI and if required, transperineal prostate biopsies. We report on the re-referral rates of men who had undergone previous investigation on the RAPID pathway. METHODS: Data from consecutive patients on the RAPID pathway (April/2017 to December/2020) was entered into the online RAPID registry. A transperineal targeted and systematic prostate biopsy (TP-Bx) was offered on the same day if the mpMRI score was 4 or 5. A score of 3 required a PSA density ≥ 0.12. The re-referral assessment was checked based on computer assistance. RESULTS: 2869 patients with mean age 66 [IQR 59-72] and mean PSA 7.5 (5.8-11.3) were referred for prostate cancer investigation. In total, 49% [1406/2869] were discharged without a suspicion of cancer. 3% (37/1196) were rereferred by their GP due to ongoing concern for prostate cancer. Mean age was 67 (46-80) and mean PSA 9.5 (1.4-19.5). From those, 13 (35%) required biopsy in addition to MRI. Four (10%) had a histological diagnosis of prostate cancer of Gleason 3+4. CONCLUSIONS: RAPID is a safe pathway in the medium term when discharging men without biopsy following a non-suspicious mpMRI. After 3 years of follow-up, the mpMRI diagnostic pathway has a low re-referral rate and even on the rereferral group, 65% still did not meet criteria for a biopsy. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e181-e181 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mariana Bertoncelli Tanaka More articles by this author Uma Walter More articles by this author David Eldred-Evans More articles by this author Edward J. Bass More articles by this author Martin J. Connor More articles by this author Pallab Sarkar More articles by this author Feargus Hoskings-Jervis More articles by this author Heather Bhola-Stewart More articles by this author Elizabeth Pegers More articles by this author Laura Powell More articles by this author Deepa Leelamany More articles by this author Kathie Wong More articles by this author Shahzad Ahmad More articles by this author Henry Tam More articles by this author Hasan Qazi More articles by this author Stephen Gordon More articles by this author David Hrouda More articles by this author Stuart McCracken More articles by this author Mathias Winkler More articles by this author Hashim U. Ahmed More articles by this author Expand All Advertisement Loading ...

Waiting Times for Prostate Cancer Diagnosis in a Nigerian Population.

Background Prostate biopsy remains an important surgical procedure in the diagnostic pathway for prostate cancer, but access to prostate biopsy service is poorly studied in the Nigerian population. While there has been a well-documented delay in patient presentation with prostate cancer in Nigeria, little is however known about how long patients wait to have a histological diagnosis of prostate cancer and start treatment after presenting at Nigerian hospitals. Method This was a descriptive retrospective study to document the specific duration of the various timelines in getting a diagnosis of prostate cancer at the Lagos State University Teaching Hospital, Ikeja, Nigeria. Results There were 270 patients. The mean age was 69.50 ± 8.03 years (range 45-90). The mean PSA at presentation was 563.2 ± 1879.2 ng/ml (range 2.05-15400), and the median PSA was 49.3 ng/ml. The median waiting times were (i) 10 days from referral to presentation; (ii) 30 days from presentation to biopsy; (iii) 24 days from biopsy to review of histology; (iv) 1 day from histology review to discussion/planning of treatment. The median overall waiting time from referral to treatment was 103 days. The mean time from presentation to biopsy was significantly shorter for patients with PSA of ≥50 ng/ml compared to those with PSA < 50 ng/ml. p = 0.048. Overall, the median time from biopsy to histology was significantly shorter for patients whose specimens were processed in private laboratories (17 days) compared to those whose specimens were processed at the teaching hospital laboratory (30 days), p ≤ 0.001. Conclusion There is a significant delay within the health care system in getting a prostate cancer diagnosis in the Nigerian population studied. The major points of the identified delay were the waiting time from patient presentation to having a biopsy done and the histology report waiting time.

UpFrontPSMA: A randomized phase II study of sequential 177Lu-PSMA617 and docetaxel versus docetaxel in metastatic hormone-naïve prostate cancer (mHNPC).

TPS180 Background: 177Lu‐PSMA-617 (Lu-PSMA) is a radiolabeled small-molecule that binds with high affinity to PSMA enabling highly targeted delivery of beta radiation to prostate cancer cells. In metastatic castration-resistant prostate cancer, Lu-PSMA showed superior activity to Cabazitaxel in the TheraP trial. Although androgen deprivation therapy (ADT) + Docetaxel is a standard of care for de novo high-volume mHNPC, outcomes remain sub-optimal for many patients. We hypothesize that Lu-PSMA prior to docetaxel will achieve a higher undetectable PSA rate at 12 months compared to docetaxel alone in men with newly-diagnosed high-volume mHNPC. Methods: UpFrontPSMA is an open label, randomized, stratified, 2-arm, multi-center, phase 2 clinical trial recruiting 140 patients at 11 Australian centers. Key eligibility criteria include histological diagnosis of prostate cancer within 12 weeks, PSA &gt; 10ng/ml at diagnosis, &lt; 4 weeks on ADT, and high-volume (≥ 4 bone metastases with ≥ 1 outside the axial skeleton, and/or visceral metastases), PSMA-avid disease on 68Ga-PSMA-11 PET/CT with no major discordance on 18FDG-PET/CT. Patients will be randomized 1:1 to the experimental arm (Lu-PSMA 7.5 GBq q6w x 2 cycles followed 6 weeks later by docetaxel 75mg/m2 q3w x 6 cycles), or standard-of-care Arm (docetaxel alone). All patients will receive continuous ADT. Assessments will be done every 3 weeks during study treatment, and then every 6-12 weeks until unequivocal disease progression. CT and whole body bone scan will be performed at baseline and every 12 weeks, 68Ga-PSMA-11 PET/CT at baseline and 12 weeks, and 18FDG-PET/CT at baseline and 12 weeks (if applicable). Correlative samples will include optional tumour tissue (baseline and disease progression), and serial plasma/whole blood collection. The primary endpoint is undetectable PSA (≤ 0.2 ng/ml) at 12 months. Secondary endpoints are safety, time to castration resistance, PSA-progression-free-survival (PSA-PFS), radiographic PFS, radiographic response rates, early PSMA-PET response rates, quality of life and overall survival. Exploratory endpoints are prognostic and predictive value of PET-derived parameters and of biomarkers identified in plasma/whole blood/tumour tissue. The study will have 85% power to reject the null hypothesis if the true 12 month undetectable PSA rate in the experimental Arm is 50%. The power calculation assumes no more than 10 patients (7%) of the 140 patients will be unevaluable or lost to follow-up in 1 year, 5% alpha and two-sided test for proportions. As of October 13, 2020, accrual stands at 4. UpFrontPSMA is an investigator-led, academic trial sponsored by Peter MacCallum Cancer Centre in collaboration with ANZUP Cancer Trials Group with study coordination provided by the Centre for Biostatistics and Clinical Trials (BaCT) Clinical trial information: NCT04343885.

Impact of 68Ga-PSMA PET/CT in the treatment of prostate cancer: Initial experience in Spain

To evaluate whether positron-emission tomography/computed tomography with 68Ga-PSMA (68Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer (PCa). Although 68Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent 68Ga-PSMA PET/CT imaging. All patients (n = 27) with a histological diagnosis of PCa who underwent 68Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017-2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the 68Ga-PSMA PET/CT were available. Most patients (n = 26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent 68Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall, 68Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests-MRI, CT, or bone scans-performed prior to the 68Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the 68Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study. 68Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.

Prospects for the development of intellectual diagnosis of prostate cancer

To date, the world’s pressing problem is the problem of timely diagnosis of cancer, allowing the patient to avoid severe complex treatment, to survive and lead his usual way of life. The article discusses the prospects for the development of intellectual diagnosis of prostate cancer. The final decision on such a diagnosis of the patient is made on the basis of the histological analysis of the tumor tissue preparation. However, at the moment there is a shortage of qualified specialists-pathologists. Hence the need to create training histological diagnosis systems to disseminate the knowledge of specialists, as well as expert systems and intelligent systems to support medical decision-making.This article considers the project of development of an expert system of histological diagnosis of prostate cancer. This intelligent system will allow experienced histologists to transfer their knowledge to younger specialists. It is assumed that this knowledge will be processed by the system in such a way that doctors will be able to quickly make a decision on the diagnosis of patients.

IMMUNOHISTOCHEMICAL ANALYSIS AS A METHOD FOR INCREASING THE DETECTION OF PROSTATE CANCER IN PRIMARY BIOPSY

Morphological manifestations of prostate cancer (PCa) in 15–20% of cases are similar to those with benign hyperplastic processes in prostate tissue and/or with a histological pattern of atypical small acinar proliferation (ASAP). The purpose of this study is a comparative study of the detection of prostate cancer in biopsy material using a review morphological analysis and immunohistochemistry with the use of monoclonal antibodies to the nuclear p63 protein, high molecular weight cytokeratins of clone 34βE12 and α-methylacyl-CoA-racemase. Materials and methods . The method of the study was a retrospective analysis of the findings on the review morpholog­ical and immunohistochemical (IHC) analyzes of biopsy material of 428 patients who were examined and treated in the urological hospital for the period from 2013 to 2017. Results . Almost half of the cases of ASAP, determined by routine histological examination of biopsy specimens with hematoxylin-eosin staining, in the process of IHC analysis using monoclonal antibodies to the nuclear protein p63, cyto­keratins of clone 34βE12 and α-methylacyl-CoA racemase were verified for prostate cancer. The number of histological findings on benign prostatic hyperplasia detected in routinely stained preparations decreased by 12.38% in favor of the histological diagnosis of prostate cancer after the IHC study. Conclusion . Immunohistochemical analysis of biopsy material using monoclonal antibodies to nuclear p63, high-molec­ular cytokeratins of clone 34βE12 and α-methylacyl-CoA racemase for suspected prostate cancer: firstly, specifies the micromorphological picture and demasks prostate cancer; secondly, it increases the detectability of prostate cancer; thirdly, it reduces the occurrence of false-negative results.

Next Generation Sequencing of urine exfoliated cells: an approach of prostate cancer microRNAs research

There is emerging evidence that microRNAs (miRNAs) dysregulation is involved in the genesis and the progression of Prostate Cancer (PCa), thus potentially increasing their use in urological clinical practice. This is the first pilot study which utilizes Illumina Deep Sequencing to examine the entire miRNAs spectrum existent in urine exfoliated prostate cells (UEPCs) of PCa patients. A total of 11 male patients with histological diagnosis of PCa were enrolled in the present study. First-catch urine (30 mL) was collected following a prostate massage. Total RNA was extracted from urine and sequenced using an HiSeq2500 System (Illumina). QPCR assay was used to validate the highest NGS results in PCA patients and in age-matched, caucasian men. Remarkably, PCA let-7 family was down-regulated (P < 0.01), compared to the controls. The results of our study support the notion of a relatively high diagnostic value of miRNA family for PCa detection, especially in the let-7 family. The present research confirmed the potential use of miRNAs as non-invasive biomarkers in the diagnosis of PCa, potentially reducing the invasiveness of actual clinical strategy.

Expert System for Histological Diagnosis of Prostate Cancer

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Grading of prostatic adenocarcinoma: current state and prognostic implications.

BackgroundDespite significant changes in the clinical and histologic diagnosis of prostate cancer, the Gleason grading system remains one of the most powerful prognostic predictors in prostate cancer. The correct diagnosis and grading of prostate cancer is crucial for a patient’s prognosis and therapeutic options. However, this system has undergone significant revisions and continues to have deficiencies that can potentially impact patient care.Main BodyWe describe the current state of grading prostate cancer, focusing on the current guidelines for the Gleason grading system and recent changes from the 2014 International Society of Urological Pathology Consensus Conference on Gleason Grading of Prostatic Carcinoma. We also explore the limitations of the current Gleason grading system and present a validated alternative to the Gleason score. The new grading system initially described in 2013 in a study from Johns Hopkins Hospital and then validated in a multi-institutional study, includes five distinct Grade Groups based on the modified Gleason score groups. Grade Group 1 = Gleason score ≤6, Grade Group 2 = Gleason score 3 + 4 = 7, Grade Group 3 = Gleason score 4 + 3 = 7, Grade Group 4 = Gleason score 8, Grade Group 5 = Gleason scores 9 and 10.ConclusionAs this new grading system is simpler and more accurately reflects prostate cancer biology, it is recommended by the World Health Organization (WHO) to be used in conjunction with Gleason grading.

Re: Quantification of Fractal Dimension and Shannon’s Entropy in Histological Diagnosis of Prostate Cancer

Re: Quantification of Fractal Dimension and Shannon’s Entropy in Histological Diagnosis of Prostate Cancer

A quantitative analysis of the prevalence of clinical depression and anxiety in patients with prostate cancer undergoing active surveillance

ObjectiveTo quantitatively determine the prevalence of anxiety and depression in men on active surveillance (AS).DesignCross-sectional questionnaire survey.SettingSecondary care prostate cancer (PCa) clinics across South, Central and Western England.Participants313 men from...

Timing of High-Dose Rate Brachytherapy With External Beam Radiotherapy in Intermediate and High-Risk Localized Prostate CAncer (THEPCA) Patients and Its Effects on Toxicity and Quality of Life: Protocol of a Randomized Feasibility Trial.

BackgroundProstate cancer is the most common cancer in males in the UK and affects around 105 men for every 100,000. The role of radiotherapy in the management of prostate cancer significantly changed over the last few decades with developments in brachytherapy, external beam radiotherapy (EBRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT). One of the challenging factors of radiotherapy treatment of localized prostate cancer is the development of acute and late genitourinary and gastrointestinal toxicities. The recent European guidelines suggest that there is no consensus regarding the timing of high-dose rate (HDR) brachytherapy and EBRT. The schedules vary in different institutions where an HDR boost can be given either before or after EBRT. Few centers deliver HDR in between the fractions of EBRT.ObjectiveAssessment of acute genitourinary and gastrointestinal toxicities at various time points to better understand if the order in which treatment modality is delivered (ie, HDR brachytherapy or EBRT first) has an effect on the toxicity profile.MethodsTiming of HDR brachytherapy with EBRT in Prostate CAncer (THEPCA) is a single-center, open, randomized controlled feasibility trial in patients with intermediate and high-risk localized prostate cancer. A group of 50 patients aged 18 years old and over with histological diagnosis of prostate cancer (stages T1b-T3BNOMO), will be randomized to one of two treatment arms (ratio 1:1), following explanation of the study and informed consent. Patients in both arms of the study will be treated with HDR brachytherapy and EBRT, however, the order in which they receive the treatments will vary. In Arm A, patients will receive HDR brachytherapy before EBRT. In Arm B (control arm), patients will receive EBRT before HDR brachytherapy. Study outcomes will look at prospective assessment of genitourinary and gastrointestinal toxicities. The primary endpoint will be grade 3 genitourinary toxicity and the secondary endpoints will be all other grades of genitourinary toxicities (grades 1 and 2), gastrointestinal toxicities (grades 1 to 4), prostate-specific antigen (PSA) recurrence-free survival, overall survival, and quality of life.ResultsResults from this feasibility trial will be available in mid-2016.ConclusionsIf the results from this feasibility trial show evidence that the sequence of treatment modality does affect the patients’ toxicity profiles, then funding would be sought to conduct a large, multicenter, randomized controlled trial.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 15835424; http://www.isrctn.com/ISRCTN15835424 (Archived by WebCite at http://www.webcitation.org/6Xz7jfg1u).

Role of information in preparing men for transrectal ultrasound guided prostate biopsy: a qualitative study embedded in the ProtecT trial.

BackgroundThe histological diagnosis of prostate cancer requires a prostate needle biopsy. Little is known about the relationship between information provided to prepare men for transrectal ultrasound guided biopsy (TRUS-Bx) and how men experience biopsy. The objectives were a) to understand men’s experiences of biopsy as compared to their expectations; and b) to propose current evidence-based information for men undergoing TRUS-Bx.MethodsBetween February 2006 and May 2008, 1,147 men undergoing a standardised 10-core transrectal ultrasound guided biopsy protocol under antibiotic cover following a PSA 3.0-19.9 ng/ml in the Prostate Testing for Cancer and Treatment (ProtecT) trial, completed questionnaires about biopsy symptoms. In this embedded qualitative study, in-depth interviews were undertaken with 85 men (mean age 63.6 yrs, mean PSA 4.5 ng/ml) to explore men’s experiences of prostate biopsy and how the experience might be improved. Interview data were analysed thematically using qualitative research methods. Findings from the qualitative study were used to guide selection of key findings from the questionnaire study in developing a patient information leaflet preparing men for biopsy.ResultsAlthough most men tolerated TRUS-Bx, a quarter reported problematic side-effects and anxiety. Side effects were perceived as problematic and anxiety arose most commonly when experiences deviated from information provided. Men who were unprepared for elements of TRUS-Bx procedure or its sequelae responded by contacting health professionals for reassurance and voiced frustration that pre-biopsy information had understated the possible severity or duration of pain/discomfort and bleeding. Findings from questionnaire and interview data were combined to propose a comprehensive, evidence-based patient information leaflet for TRUS-Bx.ConclusionsMen reported anxiety associated with TRUS-Bx or its side-effects most commonly if they felt inadequately prepared for the procedure. Data from this qualitative study and the previous questionnaire study have been used to propose an updated, comprehensive evidence-based set of information for men undergoing TRUS-Bx.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-0729-z) contains supplementary material, which is available to authorized users.