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Highlights • PSMA PET/MRI has a higher true positive rate and sensitivity than mpMRI in patients with biochemically recurrent prostate cancer. • The true positive rate for PSMA PET/MRI was significantly greater in patients who were post prostatectomy for primary treatment. • 40% of patients with a PSA value less than 0.2 ng/mL had a positive PSMA PET/MRI read compared to 9% on MRI., Background The primary objective was to compare the overall diagnostic performance, presented as detection rate of 68Ga-PSMA-HBED-CC positron emission tomography/magnetic resonance imaging (PSMA PET/MRI) versus conventional, multiparametric MRI (mpMRI) in a population of patients with biochemically recurrent prostate cancer. In conjunction with this analysis, secondary objectives included the evaluation of the detection rate stratified by PSA levels and primary treatment modality. Methods A total of 165 PSMA PET MRI were performed from April 2018 to May 2021, of whom 108 were presenting for biochemical recurrent disease. The PSMA PET vertex to thigh were read by two different board-certified nuclear medicine physicians while the MRI head and neck, chest, abdomen, and pelvis (with dedicated, PI-RADS compliant multiparametric prostate MRI) were read by two board certified diagnostic radiologists. Analysis PSMA PET/MRI had a higher detection rate than mpMRI when evaluating patients with biochemical recurrence (BCR) with similar results demonstrated when sub-analysis was performed using PSA levels, primary treatment modality, and time since androgen deprivation therapy. Our study also showed PSMA PET/MRI had a higher sensitivity than mpMRI. Discussion Our findings demonstrate that PSMA PET/MRI is a better imaging modality in the detection of disease in the setting of BCR when compared to MRI alone. Combined utility with PSMA PET/MRI is a powerful tool which can aid in not only the detection of disease, but also guide in treatment planning for prostate cancer patients., Graphical abstract Image, graphical abstract

Highlights • Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated. • We enrolled 24 studies with 2307 eligible patients for a systemic review and meta-analysis. • AR-V7 positivity was associated with higher Gleason score, bone or any site metastasis, presence of pain and worse ECOG performance score in CRPC. • Therefore, AR-V7 positivity may be a particular type of prostate cancer subtype in CRPC., Background Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated. Objective This study aimed at evaluating the clinicopathological features of AR-V7 in CRPC patients. Materials and methods To evaluate the clinicopathological features of AR-V7 in CRPC patients. A search of PubMed, Embase, and Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma, AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Twenty-four trials published by February 2020 were included in this study. Results The proportion of Gleason score ≥ 8 was found to be significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25–2.25, p

Dysregulation of S100A8 is described in many different human tumor types, but its role in prostate cancer is unknown. To evaluate the clinical relevance of S100A8 expression in prostate cancer, a tissue microarray containing 13,665 tumors was analyzed by immunohistochemistry. Cytoplasmic S100A8 staining was compared to prostate cancer phenotype, patient prognosis and molecular features including TMPRSS2:ERG fusion status and deletions of PTEN, 3p, 5q and 6q. S100A8 immunostaining was typically seen in normal prostate tissue but lost in 60% of 9786 interpretable prostate cancers. In the remaining tumors, S100A8 was considered weak in 17.9%, moderate in 17.8% and strong in 5.4% of cases. Loss of S100A8 expression was linked to advanced tumor stage, high Gleason grade, positive nodal status, positive surgical margin and high preoperative PSA (P

Prostate cancer is the fifth most common malignancy worldwide and the second most common in men. It usually metastasizes to bony skeleton, followed by lung, liver, pleura and adrenals. We report a 71 year old male patient who initially presented only with retroperitoneal lymphadenopathy and constitutional symptoms, misleading the diagnosis of retroperitoneal lymphoma. Who later on was discovered to have carcinoma prostate.

Background MicroRNAs(miRNAs) are involved in the formation, maintenance, and metastasis of urologic cancer. Here, we aim to gather and evaluate all of the evidence regarding the potential role of miRNAs as novel predictors of urologic cancer survival. Methods A systematic review was performed to identify and score all of the published studies that evaluated the prognostic effects of miRNAs in kidney (KCa), bladder (BCa) or prostate cancer (PCa). Where appropriate, the summary effects of miRNAs on urologic cancer were meta-analysed. The reliability of those results was then further validated by an integrated analysis of the TCGA cohort and miRNA panel. Results Of 151 datasets, 80 miRNAs were enrolled in this systematic review. A meta-analysis of the prognostic qualities of each miRNA identified an objective association between miRNA and prognosis. miR-21 was identified as an unfavourable miRNA with the overall survival (HR:2.699, 1.76–4.14, P

Introduction Isolated lung metastases from prostate cancer without any other organ involvement are rare. They are commonly in the form of diffuse or multiple lesions and rarely emerge as a solitary pulmonary nodule. Presentation of case A 61-year-old man who had undergone a laparoscopic-assisted radical prostatectomy for prostate cancer 16 months prior presented with a growing solitary pulmonary nodule. Positron emission tomography/computed tomography showed an abnormal uptake in the nodule without any other organ involvement. A surgical specimen by a thoracoscopic wedge resection proved a diagnosis of a metastasis from prostate cancer. He is currently alive only with worsening pulmonary metastases at 7 years after the lung surgery. Discussion A rare entity of isolated pulmonary metastases could be a sole finding of metastatic prostate cancer over the years and its initial manifestation could emerge as a solitary pulmonary nodule. It poses a diagnostic challenge because primary lung cancer is the leading differential diagnosis of solitary pulmonary nodules and is also one of the most frequent second primary malignancies in prostate cancer survivors. Conclusion An aggressive surgical biopsy is essential for definitive histopathological and immunohistochemical analyses of solitary pulmonary nodules to distinguish a rare form of an isolated pulmonary relapse from a second primary lung cancer in prostate cancer survivors., Highlights • Isolated pulmonary metastasis without bone involvement from prostate cancer may rarely emerge as a solitary pulmonary nodule. • Primary lung cancer is a leading differential diagnosis of solitary pulmonary nodules in general and is also one of the most frequent second primary malignancies in prostate cancer survivors. • A surgical lung biopsy is a feasible option for a definitive histoimmunological diagnosis of solitary pulmonary nodules to distinguish a rare form of an isolated pulmonary metastasis from a second primary lung cancer in prostate cancer survivors.

Nanowires (NWs)-based field-effect transistors (FETs) have attracted considerable interest to develop innovative biosensors using NWs of different materials (i.e. semiconductors, polymers, etc.). NWs-based FETs provide significant advantages over the other bulk or non-NWs nanomaterials-based FETs. As the building blocks for FET-based biosensors, one-dimensional NWs offer excellent surface-to-volume ratio and are more suitable and sensitive for sensing applications. During the past decade, FET-based biosensors are smartly designed and used due to their great specificity, sensitivity, and high selectivity. Additionally, they have the advantage of low weight, low cost of mass production, small size and compatible with commercial planar processes for large-scale circuitry. In this respect, we summarize the recent advances of NWs-based FET biosensors for different biomolecule detection i.e. glucose, cholesterol, uric acid, urea, hormone, proteins, nucleotide, biomarkers, etc. A comparative sensing performance, present challenges, and future prospects of NWs-based FET biosensors are discussed in detail., Highlights • This review paper summarizes the recent advances of NWs-based FETs for biological sensors. • The sensing applications of NWs-based FETs for various important biomolecules are discussed. • The present challenges and further prospects of NWs-based FETs are also highlighted.

Highlights • We report on long-term toxicity of salvage radiotherapy with a focus on incontinence. • Salvage radiotherapy results in good long-term biochemical control. • Toxicity and urinary incontinence rates are high after salvage radiotherapy., Purpose For patients with local recurrent disease after radical prostatectomy (35–54%) salvage radiotherapy (SRT) is the treatment of choice. In the post prostatectomy setting, SRT may impose risk at increased toxicity. As data on long-term toxicity, especially on urinary incontinence, are scarce, we report on the long-term treatment outcomes, toxicity and urinary incontinence rates after SRT. Materials and methods Patients with biochemically recurrent prostate cancer after radical prostatectomy, who were treated with SRT (3D-CRT) at our institution between 1998 and 2012, were included in this retrospective cohort analysis. Primary endpoint was urinary incontinence rate. Secondary endpoints were acute and late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicity rates, biochemical progression-free survival (bPFS), distant metastasis-free survival (DMFS), disease specific survival (DSS), and overall survival (OS). Results 244 patients were included. Median follow-up after SRT was 50 months (range: 4–187 months). Before start of SRT 69.7% of patients were continent for urine. After SRT de novo urinary incontinence complaints (grade ≥ 1) occurred in the respective acute and late phase in 6.1% and 17.6% of patients. Respective acute grade ≥2 GU and GI toxicity was 19.2% and 17.6%. Late grade ≥2 toxicity for GU was 29.9% and for GI was 21.3%, respectively. The respective 5-year bPFS, OS, DSS and DMFS rates were 47.6%, 91.8%, 98.8% and 80.5%. Conclusions Experience at our institution with SRT demonstrates that this results in good long-term biochemical control. However, toxicity and urinary incontinence rates were high.

Highlights • Lymphocele after radical prostatectomy leading major complications is rare. • Lymphocele is the most common cause of hospital readmission after radical prostatectomy. • Lymphocele can be seen in atypical regions after radical prostatectomy. • Percutaneous interventions can be used for pelvic lymphocele treatment., Introduction A pelvic lymphocele is a collection of lymphatic fluid that develops after extensive lymphadenectomies in surgeries such as urological malignancies or renal transplantation. Pelvic lymphoceles may cause complications such as fever, abdominal pain, leg swelling, genital swelling and flank pain. This report summarizes the management of a pelvic lymphocele after open radical retropubic prostatectomy with bilateral lymphadenectomy. Presentation of case Herein, we present a case in which a pelvic lymphocele developed seven months post-radical open retropubic prostatectomy and through this patient we discussed the lymphocele following radical prostatectomy. The pelvic lymphocele occurred along the sciatic nerve from the sciatica foramen to the intergluteal muscles. The patient was treated with three drainage catheters. This localization is an atypical and unusual for lymphocele after radical retropubic prostatectomy. Discussion Lymphocele formation that leads to major complications after radical prostatectomy is rare. Lymphocele formation is most commonly seen in the early postoperative period, but it should be considered in patients with fever, abdominal pain or leg swelling during the late postoperative period. Lymphocele formation was the most common cause of hospital readmission after radical prostatectomy. Conclusion Lymphocele formation can be seen in atypical regions and can lead to unexpected complications after radical prostatectomy. Therefore, it should be brought to mind when complaints such as fever and lower extremity swelling occurred in patients underwent extensive lymph node dissection. Surgical treatment options are available, but percutaneous interventions can also be used.

Prostatic PIRADS 4 and 5 lesions on multiparametric MRI typically represent adenocarcinoma with small lymphocytic lymphoma being a rare pathological finding. We report a case of small lymphocytic lymphoma masquerading as PIRADS 4 and 5 lesions with associated lymphadenopathy in a 69-year-old male on active surveillance for low-risk prostate cancer that was subsequently confirmed on targeted and systematic prostate biopsy. Following treatment of lymphoma with ibrutinib, there was complete resolution of the PIRADS lesions on follow-up mpMRI.

Biglycan (BGN), a proteoglycan of the extracellular matrix, is included in mRNA signatures for prostate cancer aggressiveness. To understand the impact of BGN on prognosis and its relationship to molecularly defined subsets, we analyzed BGN expression by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Seventy-eight percent of 11,050 interpretable cancers showed BGN expression, which was considered as low intensity in 47.7% and as high intensity in 31.1% of cancers. BGN protein expression rose with increasing pathological tumor stage, Gleason grade, lymph node metastasis and early PSA recurrence (P

Objectives A request to report laboratory values to a specific number of decimal places represents a delicate balance between clinical interpretation of a true analytical change versus laboratory understanding of analytical imprecision and significant figures. Prostate specific antigen (PSA) was used as an example to determine if an immunoassay routinely reported to the hundredths decimal place based on significant figure assessment in our laboratory was capable of providing analytically meaningful results when reported to the thousandths places when requested by clinicians. Design and methods Results of imprecision studies of a representative PSA assay (Roche MODULAR E170) employing two methods of statistical analysis are reported. Sample pools were generated with target values of 0.01 and 0.20 μg/L PSA as determined by the E170. Intra-assay imprecision studies were conducted and the resultant data were analyzed using two independent statistical methods to evaluate reporting limits. Results These statistical methods indicated reporting results to the thousandths place at the two assessed concentrations was an appropriate reflection of the measurement imprecision for the representative assay. This approach used two independent statistical tests to determine the ability of an analytical system to support a desired reporting level. Importantly, data were generated during a routine intra-assay imprecision study, thus this approach does not require extra data collection by the laboratory. Conclusions Independent statistical analysis must be used to determine appropriate significant figure limitations for clinically relevant analytes. Establishing these limits is the responsibility of the laboratory and should be determined prior to providing clinical results., Highlights • Clinicians may request results to more decimal places than labs routinely report. • PSA is an example of an analyte that may be reported to multiple decimal places. • Two statistical approaches verified PSA assay precision to the thousandths place. • Data distribution was not affected by reporting to either 2 or 3 decimal places. • Responsibility of reporting unit magnitude lies with each clinical laboratory.

The A Disintegrin and Metalloproteinase (ADAM) family of endopeptidases plays a role in many solid cancers and includes promising targets for anticancer therapies. Deregulation of ADAM15 has been linked to tumor aggressiveness and cell line studies suggest that ADAM15 overexpression may also be implicated in prostate cancer. To evaluate the impact of ADAM15 expression and its relationship with key genomic alterations, a tissue microarray containing 12,427 prostate cancers was analyzed by immunohistochemistry. ADAM15 expression was compared to phenotype, prognosis and molecular features including TMPRSS2:ERG fusion and frequent deletions involving PTEN, 3p, 5q and 6q. Normal prostate epithelium did not show ADAM15 staining. In prostate cancers, negative, weak, moderate, and strong ADAM15 staining was found in 87.7%, 3.7%, 5.6%, and 3.0% of 9826 interpretable tumors. Strong ADAM15 staining was linked to high Gleason grade, advanced pathological tumor stage, positive nodal stage and resection margin. ADAM15 overexpression was also associated with TMPRSS2:ERG fusions and PTEN deletions (P

We report a case with prostate cancer and gastric neuroendocrine carcinoma. A 72-year old male presented with a gastric lesion 5 months after radical prostatectomy. The lesion was immunohistochemically positive for PSA, alpha-methylacyl-CoA racemase, synaptophysin, and chromogranin A, but negative for androgen receptor (AR). Differentiating gastric neuroendocrine carcinoma from gastric metastasis of prostate cancer is difficult, as both lesions exhibit similar acinar cell proliferation with prominent nucleoli.1 We discuss the diagnostic process of this case and how AR was a useful specific marker for diagnosing primary gastric neuroendocrine carcinoma. Keywords: Gastric neuroendocrine carcinoma, Immunohistochemistry, Prostate cancer

Highlights • Bone metastases negatively impact on patients’ quality of life (QoL). • Skeletal related events have a detrimental effect on both QoL and survival. • Both local and systemic treatments are often required to manage bone metastases. • Bone turnover modulators reduce the risk of skeletal complications and improve pain. • Novel agents may deserve further investigation for the management of bone metastases., Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

Cancer remains one of the most challenging diseases, as many patients show limited therapeutic response to treatment. Liquid biopsy is a minimally invasive method that has the advantage of providing real-time disease information with the least damage to cancer patients. Extracellular vesicles (EVs) released by the parental cells and protected by lipid bilayer membrane structure represent an emerging liquid biopsy modality. Apart from promoting cell growth, proliferation, and migration, EVs and their cargos (mainly miRNAs and proteins) are also biomarkers for cancer diagnosis and prognosis. Furthermore, their alterations pre- and post-therapy can guide therapeutic strategy determinations for better-stratified therapy. In this review, we summarize the potential clinical significance of EVs and their cargos in therapeutic response monitoring and prediction in several cancers (mainly lung cancer, prostate cancer, breast cancer, melanoma, lymphoma, glioblastoma, and head and neck squamous cell carcinoma) and discuss the questions that require future investigation.

Dendritic cells (DCs) are major antigen-presenting cells that can efficiently prime and cross-prime antigen-specific T cells. Delivering antigen to DCs via surface receptors is thus an appealing strategy to evoke cellular immunity. Nonetheless, which DC surface receptor to target to yield the optimal CD8+ and CD4+ T cell responses remains elusive. Herein, we report the superiority of CD40 over 9 different lectins and scavenger receptors at evoking antigen-specific CD8+ T cell responses. However, lectins (e.g., LOX-1 and Dectin-1) were more efficient than CD40 at eliciting CD4+ T cell responses. Common and distinct patterns of subcellular and intracellular localization of receptor-bound αCD40, αLOX-1 and αDectin-1 further support their functional specialization at enhancing antigen presentation to either CD8+ or CD4+ T cells. Lastly, we demonstrate that antigen targeting to CD40 can evoke potent antigen-specific CD8+ T cell responses in human CD40 transgenic mice. This study provides fundamental information for the rational design of vaccines against cancers and viral infections., Highlights • Antigen delivery to DCs via CD40 is more efficient than through nine other receptors at eliciting CD8 T+ cell response. • Antigen delivery via lectins (e.g., LOX-1 and Dectin-1) is more efficient than CD40 at eliciting CD4+ T cell responses. The success of an immunotherapeutic vaccine for cancer is largely dependent on its ability to evoke potent cellular immunity. Although targeting antigens to dendritic cells (DCs) has been known to be an efficient strategy to evoke cellular immunity, which targeted receptors yield the optimal cellular immunity remained elusive. We report that targeting CD40, compared to 9 other DC receptors, results in the greatest levels of CD8+ cytotoxic T cell responses, while targeting lectins results in enhanced CD4+ helper T cell responses. The findings of this study will assist us in the rational design of immunotherapeutic vaccines against cancers.

Approximately 25% of patients who have undergone extensive systemic therapy for advanced metastatic castration-resistant prostate cancer (mCRPC) develop treatment associated neuroendocrine prostate cancer (NEPC). 177Lu-prostate specific membrane antigen (-PSMA) is an emerging alternative therapy for mCRPC patients who have exhausted other systemic therapy options; however, cells with neuroendocrine differentiation do not express PSMA and are not affected by this treatment. This case highlights an exceptional response of skeletal metastases to 177LuPSMA that is undermined by neuroendocrine transformation in the liver.

We describe the case of a 54-year-old man with nodal recurrence prostate cancer after radical prostatectomy, salvage external-beam radiotherapy and salvage lymph node dissection. The patient was evaluated with a lymphotropic ultrasmall superparamagnetic particles of iron oxide (USPIO)-MRI and a 68Ga radiolabelled prostate specific membrane antigen (Ga68-PSMA) PET-CT scan which enhanced persistent localized nodal disease. The patient was then considered for a second robot-assisted extended S-LND. Differently from preoperative imaging, pathology report revealed a wide nodal involvement mirroring a metastatic disease. The current manuscript is an explanatory case on the limitations of lymph node imaging in prostate cancer recurrence.

Introduction: Prostate biopsy, usually performed by a transrectal approach, is executed when there is a suspicion of prostate cancer. Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation and only 19% of them are localized in the rectum. Case report: The authors describe a 73-year-old man without a significant past medical history that underwent a prostate biopsy because of urinary complaints and elevated serum levels of prostate specific antigen. The histology revealed a well-differentiated NET characterized as a low-grade tumor (G1). A total colonoscopy revealed a 5 mm sessile rectal polyp and in the splenic flexure a sessile lesion with central ulceration with 5 cm with histological features compatible with an adenocarcinoma. Conclusion: This is the first case reported in the literature of a rectal NET diagnosed by transrectal prostate biopsy. This case is particularly unique because the diagnosis of the NET lead to the subsequent timely detection of a colonic adenocarcinoma. © 2015 Sociedade Portuguesa de Gastrenterologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Ectopic ureter and ureterocele are rare congenital anomalies. As such, are seldom encountered incidentally during urologic surgery. We present a case illustrating an unforeseen encounter of an ectopic ureter with an associated ureterocele during a robotic assisted laparoscopic prostatectomy (RALP) and the surgical technique used to adapt to the anatomical variation.

This review summarizes the role of extracellular calcium, as found present in the bone tissue, in the process of bone metastasis.

Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer.Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for their potential diagnostic, prognostic and predictive roles.In this review, we summarize the pathogenesis of BM in breast, prostate and lung tumours, while exploring the current research focused on the identification and clinical validation of BM biomarkers. Keywords: Bone metastasis, Biomarkers, Bone turnover markers, Breast cancer, Prostate cancer, Lung cancer

Abnormal expression and function of chromatin regulators results in the altered chromatin structure seen in cancer. The chromatin regulator CTCF, its cofactor CHD8, and antagonistic paralogue BORIS have wide-ranging effects on gene regulation. Their concurrent expression and regulation was examined in benign, localized, and metastatic prostate cancer (PCa) arrays with extended follow-up using an automated quantitative imaging system, VECTRA. Epithelial staining was quantified and compared against a range of clinicopathologic variables. CHD8 expression was decreased in HGPIN, localized, and metastatic PCa compared to benign (P < .001). CHD8 promoter hypermethylation, assessed by Quantitative Pyrosequencing, occurred in over 45% of primary cancers in this population as well as the TGCA database. Treatment of cell lines with the demethylating agent 5-Aza-2′-deoxycytidine reinduced expression. An interesting dichotomy for CHD8 was observed within primary cancers, with higher nuclear protein expression associated with adverse clinical outcomes including extracapsular extension (P = .007), presence of metastases (P = .025) and worse PSA-recurrence free survival (P = .048). CHD8 outperformed Gleason score and predicted biochemical failure within intermediate grade prostate cancers. The BORIS/CTCF expression ratio increased in localized (P = .03) and metastatic PCa (P = .006) and was associated with higher Gleason score (P = .02), increased tumor volume (P = .02) and positive margins (P = .04). Per cell heterogeneity of expression revealed all protein expression to be more heterogeneous in cancerous tissue (both P < .001), especially high grade (P < .01). In the first detailed analysis in cancer, a marked loss of CHD8 expression and increased BORIS/CTCF ratio indicate frequent disruption of CTCF and its effector genes in PCa.

Highlights • Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening. • MRI is specific for detecting prostate cancer in men with increased genetic risk. • Detection of prostate cancer in men at genetically low risk with MRI is limited., Background Diffusion-weighted (DW)-MRI is invaluable in detecting prostate cancer. We determined its sensitivity and specificity and established interobserver agreement for detecting tumour in men with a family history of prostate cancer stratified by genetic risk. Methods 51 men with a family history of prostate cancer underwent T2-W + DW-endorectal MRI at 3.0 T. Presence of tumour was noted at right and left apex, mid and basal prostate sextants by 2 independent observers, 1 experienced and the other inexperienced in endorectal MRI. Sensitivity and specificity against a 10-core sampling technique (lateral and medial cores at each level considered together) in men with >2× population risk based on 71 SNP analysis versus those with lower genetic risk scores was established. Interobserver agreement was determined at a subject level. Results Biopsies indicated cancer in 28 sextants in 13/51 men; 32 of 51 men had twice the population risk (>0.25) based on 71 SNP profiling. Sensitivity/specificity per-subject for patients was 90.0%/86.4% (high-risk) vs. 66.7%/100% (low-risk, observer 1) and 60.0%/86.3% (high-risk) vs. 33.3%/93.8% (low-risk, observer 2) with moderate overall inter-observer agreement (kappa = 0.42). Regional sensitivities/specificities for high-risk vs. low-risk for observer 1 apex 72.2%/100% [33.3%/100%], mid 100%/93.1% [100%/97.3%], base 16.7%/98.3% [0%/100%] and for observer 2 apex 36.4%/98.1% [0%/100%], mid 28.6%/96.5% [100%/100%], base 20%/100% [0%/97.3%] were poorer as they failed to detect multiple lesions. Conclusion Endorectal T2W + DW-MRI at 3.0 T yields high sensitivity and specificity for tumour detection by an experienced observer in screening men with a family history of prostate cancer and increased genetic risk.