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Background In men suspected of having prostate cancer (PCa), up to 50% of men with positive multiparametric MRI (mpMRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] or Likert score of 3 or higher) have no clinically significant (Gleason score ≤3+3, benign) biopsy findings. Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI analysis could improve the stratification of positive mpMRI findings. Purpose To evaluate VERDICT MRI, mpMRI-derived apparent diffusion coefficient (ADC), and prostate-specific antigen density (PSAD) as determinants of clinically significant PCa (csPCa). Materials and Methods Between April 2016 and December 2019, men suspected of having PCa were prospectively recruited from two centers and underwent VERDICT MRI and mpMRI at one center before undergoing targeted biopsy. Biopsied lesion ADC, lesion-derived fractional intracellular volume (FIC), and PSAD were compared between men with csPCa and those without csPCa, using nonparametric tests subdivided by Likert scores. Area under the receiver operating characteristic curve (AUC) was calculated to test diagnostic performance. Results Among 303 biopsy-naive men, 165 study participants (mean age, 65 years ± 7 [SD]) underwent targeted biopsy; of these, 73 had csPCa. Median lesion FIC was higher in men with csPCa (FIC, 0.53) than in those without csPCa (FIC, 0.18) for Likert 3 (iP/i= .002) and Likert 4 (0.60 vs 0.28,iP/ilt; .001) lesions. Median lesion ADC was lower for Likert 4 lesions with csPCa (0.86 × 10sup-3/supmmsup2/sup/sec) compared with lesions without csPCa (1.12 × 10sup-3/supmmsup2/sup/sec,iP/i= .03), but there was no evidence of a difference for Likert 3 lesions (0.97 × 10sup-3/supmmsup2/sup/sec vs 1.20 × 10sup-3/supmmsup2/sup/sec,iP/i= .09). PSAD also showed no difference for Likert 3 (0.17 ng/mLsup2/supvs 0.12 ng/mLsup2/sup,iP/i= .07) or Likert 4 (0.14 ng/mLsup2/supvs 0.12 ng/mLsup2/sup,iP/i= .47) lesions. The diagnostic performance of FIC (AUC, 0.96; 95% CI: 0.93, 1.00) was higher (iP/i= .02) than that of ADC (AUC, 0.85; 95% CI: 0.79, 0.91) and PSAD (AUC, 0.74; 95% CI: 0.66, 0.82) for the presence of csPCa in biopsied lesions. Conclusion Lesion fractional intracellular volume enabled better classification of clinically significant prostate cancer than did apparent diffusion coefficient and prostate-specific antigen density. Clinical trial registration no. NCT02689271 © RSNA, 2022iOnline supplemental material is available for this article./i

Background The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. Purpose To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. Materials and Methods In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3-5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. Results Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9

OBJECTIVE: To investigate whether patients with Gleason 3 + 4 cancer on transrectal biopsy are upgraded after undergoing transperineal magnetic resonance imaging (MRI)-targeted biopsy and whether this has implications for current clinical practice. PATIENTS AND METHODS: In this retrospective analysis we examined 107 consecutive patients presenting at a single tertiary referral centre (July 2012 to July 2016) with prostate cancer of Gleason score 3 + 4 on transrectal ultrasonography (TRUS)-guided systematic non-targeted biopsy who then underwent a multiparametric MRI followed by MRI-targeted transperineal prostate biopsy for accurate risk stratification and localization. RESULTS: The patients' mean (sd) age was 67.0 (8.0) years, and they had a median (interquartile range) PSA concentration of 6.2 (4.7-9.6) ng/mL. Of the 107 patients, 84 (78.5%) had Gleason 3 + 4 on both transrectal systematic biopsy and transperineal MRI-targeted biopsy. Nineteen patients (17.8%) were upgraded to Gleason 4 + 3, three patients (3.0%) to Gleason 4 + 4 and one patient (1.0%) to Gleason 4 + 5. These differences were significant (P = 0.0006). Likewise, 23/107 patients (22%) had higher-risk disease based on their targeted biopsies. CONCLUSION: The use of targeted biopsy in men with impalpable cancer, ultimately upgraded one in five patients from favourable-intermediate- to unfavourable-intermediate-risk disease or worse. This has significant clinical implications for men considering active surveillance or radical treatment. Our risk calculators must now be validated using these data from targeted biopsy as the technique becomes widely adopted.

Objectives: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. Methods: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. Results: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged &lt, 50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. Conclusions: The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing.

Background Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. Methods During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. Results 500 patients underwent surgery with median age 62.5 (IQR 51–71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. Conclusion It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration., Highlights • Priority surgeries are being cancelled every week due to the COVID-19 pandemic. • A multicentre surgical referral network was set up as part of an NHS England approach to continuing safe surgery • The referral network consisted of 14 NHS trusts and surgery was performed at a single COVID-19 ‘cold site’. • After 500 surgeries performed, there was a 0% 30-day mortality from COVID-19. • It is safe to continue cancer and priority surgery during the COVID-19 pandemic with appropriate service reconfiguration.

Prostate Cancer is now the second biggest cause of cancer mortality in the UK. Media coverage has been rising, with some attributing to a rise in the cases diagnosed and treated in the NHS down to the "Fry and Turnbull effect". Our understanding of prostate cancer has increased tremendously in the past decades, with advances in molecular biology and genomics driving the way to new treatments and diagnostics. This Special Edition of Translational Andrology and Urology 2019: Prostate Cancer Biology and Genomics aims to review the current state of prostate cancer genomics, proteomics, diagnostics and treatment.

We consider the current and future role of transrectal ultrasound imaging in the diagnosis of prostate cancer, with a particular focus on the pre-biopsy localization and targeting role that multiparametric MRI (mpMRI) has come to occupy for some men in recent years. We draw a distinction between transrectal ultrasound (TRUS) used only as a means of distributing zonal biopsies with its employment as a means for identifying and targeting sonographically abnormal lesions. The role of AI in lesion identification and targeting will be reviewed. Comparisons of cost and availability, frequency of contraindications and diagnostic accuracy between these two imaging modalities will be drawn.

Background Multiparametric magnetic resonance imaging (mpMRI) is now recommended prebiopsy in numerous healthcare regions based on the findings of high-quality studies from expert centres. Concern remains about reproducibility of mpMRI to rule out clinically significant prostate cancer (csPCa) in real-world settings. Objective To assess the diagnostic performance of mpMRI for csPCa in a real-world setting. Design, setting, and participants A multicentre, retrospective cohort study, including men referred with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination who had undergone mpMRI followed by transrectal or transperineal biopsy, was conducted. Patients could be biopsy naive or have had previous negative biopsies. Outcome measurements and statistical analysis The primary definition for csPCa was International Society of Urological Pathology (ISUP) grade group (GG) ≥2 (any Gleason ≥7); the accuracy for other definitions was also evaluated. Results and limitations Across ten sites, 2642 men were included (January 2011–November 2018). Mean age and PSA were 65.3 yr (standard deviation [SD] 7.8 yr) and 7.5 ng/ml (SD 3.3 ng/ml), respectively. Of the patients, 35.9% had “negative MRI” (scores 1–2); 51.9% underwent transrectal biopsy and 48.1% had transperineal biopsy, with 43.4% diagnosed with csPCa overall. The sensitivity and negative predictive value (NPV) for ISUP GG ≥ 2 were 87.3% and 87.5%, respectively. The NPVs were 87.4% and 88.1% for men undergoing transrectal and transperineal biopsy, respectively. Specificity and positive predictive value of MRI were 49.8% and 49.2%, respectively. The sensitivity and NPV increased to 96.6% and 90.6%, respectively, when a PSA density threshold of 0.15 ng/ml/ml was used in MRI scores 1–2; these metrics increased to 97.5% and 91.2%, respectively, for PSA density 0.12 ng/ml/ml. ISUP GG ≥ 3 (Gleason ≥4 + 3) was found in 2.4% (15/617) of men with MRI scores 1–2. They key limitations of this study are the heterogeneity and retrospective nature of the data. Conclusions Multiparametric MRI when used in real-world settings is able to rule out csPCa accurately, suggesting that about one-third of men might avoid an immediate biopsy. Men should be counselled about the risk of missing some significant cancers. Patient summary Multiparametric magnetic resonance imaging (MRI) is a useful tool for ruling out prostate cancer, especially when combined with prostate-specific antigen density (PSAD). Previous results published from specialist centres can be reproduced at smaller institutions. However, patients and their clinicians must be aware that an early diagnosis of clinically significant prostate cancer could be missed in nearly 10% of patients by relying on MRI and PSAD alone.

OBJECTIVE: To compare the proportion of clinically significant prostate cancers (PCa) found in lesions detected by multiparametric MRI (mpMRI) with that found in lesions detected by multiparametric ultrasound (mpUSS), in men at risk. PATIENTS AND METHODS: CADMUS (Cancer Detection by Multiparametric Ultrasound of the prostate) is a prospective, multi-centre paired cohort diagnostic utility study with built-in randomisation of order of biopsies. The trial is registered ISRCTN38541912. All patients will undergo the index test under evaluation (mpUSS±biopsies), as well as the standard test (mpMRI±biopsies). Eligible men will be those at risk of harbouring prostate cancer usually recommended for prostate biopsy, either for the first time or as a repeat, who have not had any prior treatment for prostate cancer. Men in need of repeat biopsy will include those with prior negative results but ongoing suspicion, and those with an existing prostate cancer diagnosis but a need for accurate risk stratification. Both scans will be reported blind to the results of the other and the order in which the targeted biopsies derived from the two different imaging modalities are taken will be randomised. Comparison will be drawn between biopsy results of lesions detected by mpUSS with those lesions detected by mpMRI. Agreement over position between the two imaging modalities will be studied. DISCUSSION: CADMUS will provide level one evidence on the performance of mpUSS derived targeted biopsies in the identification of clinically significant prostate cancer in comparison to mpMRI targeted biopsies. Recruitment is underway and expected to complete in 2018.

Prostate specific antigen testing results in unnecessary biopsy and over diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure associated with significant morbidity. More accurate noninvasive or minimally invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly to predict clinically significant prostate cancer in prebiopsy cases.We enrolled 155 treatment naïve patients with prostate cancer and 98 before biopsy for circulating tumor cell enumeration. RNA was extracted from circulating tumor cells of 184 patients for gene expression analysis. The Kruskal-Wallis and Spearman rank tests, multivariate logistic regression and the random forest method were applied to assess the association of circulating tumor cells with aggressive prostate cancer.Of patients with localized prostate cancer 54% were scored as having positive circulating tumor cells, which was associated with a higher Gleason score (p=0.0003), risk group (p0.0001) and clinically significant prostate cancer (p0.0001). In the prebiopsy group a positive circulating tumor cell score combined with prostate specific antigen predicted clinically significant prostate cancer (AUC 0.869). A 12-gene panel prognostic for clinically significant prostate cancer was also identified. When combining the prostate specific antigen level, the circulating tumor cell score and the 12-gene panel, the AUC of clinically significant prostate cancer prediction was 0.927. Adding those data to cases with available multiparametric magnetic resonance imaging data significantly increased prediction accuracy (AUC 0.936 vs 0.629).Circulating tumor cell analysis has the potential to significantly improve patient stratification by prostate specific antigen and/or multiparametric magnetic resonance imaging for biopsy and treatment.

Background Biologic specificity of diffusion MRI in relation to prostate cancer aggressiveness may improve by examining separate components of the diffusion MRI signal. The Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors (VERDICT) model estimates three distinct signal components and associates them to (a) intracellular water, (b) water in the extracellular extravascular space, and (c) water in the microvasculature. Purpose To evaluate the repeatability, image quality, and diagnostic utility of intracellular volume fraction (FIC) maps obtained with VERDICT prostate MRI and to compare those maps with apparent diffusion coefficient (ADC) maps for Gleason grade differentiation. Materials and Methods Seventy men (median age, 62.2 years; range, 49.5-82.0 years) suspected of having prostate cancer or undergoing active surveillance were recruited to a prospective study between April 2016 and October 2017. All men underwent multiparametric prostate and VERDICT MRI. Forty-two of the 70 men (median age, 67.7 years; range, 50.0-82.0 years) underwent two VERDICT MRI acquisitions to assess repeatability of FIC measurements obtained with VERDICT MRI. Repeatability was measured with use of intraclass correlation coefficients (ICCs). The image quality of FIC and ADC maps was independently evaluated by two board-certified radiologists. Forty-two men (median age, 64.8 years; range, 49.5-79.6 years) underwent targeted biopsy, which enabled comparison of FIC and ADC metrics in the differentiation between Gleason grades. Results VERDICT MRI FIC demonstrated ICCs of 0.87-0.95. There was no significant difference between image quality of ADC and FIC maps (score, 3.1 vs 3.3, respectively; P = .90). FIC was higher in lesions with a Gleason grade of at least 3+4 compared with benign and/or Gleason grade 3+3 lesions (mean, 0.49 ± 0.17 vs 0.31 ± 0.12, respectively; P = .002). The difference in ADC between these groups did not reach statistical significance (mean, 1.42 vs 1.16 × 10-3 mm2/sec; P = .26). Conclusion Fractional intracellular volume demonstrates high repeatability and image quality and enables better differentiation of a Gleason 4 component cancer from benign and/or Gleason 3+3 histology than apparent diffusion coefficient. Online supplemental material is available for this article. See also the editorial by Sigmund and Rosenkrantz in this issue.

5008 Background: Multiparametric MRI (mpMRI) of the prostate followed by targeted biopsy is recommended in men at risk of prostate cancer. Dissemination of this pathway may be limited by cost, variable scan and reporting quality, and contraindicated in the presence of metallic implants and claustrophobia. Multi-parametric ultrasound (mpUSS) is a point of care test with low cost that combines b-mode, colour Doppler, elastography and contrast enhancement. CADMUS compared the diagnostic performance of mpUSS to mpMRI. Methods: CADMUS recruited 370 patients from seven sites to a prospective, multicentre, paired-cohort trial (ISRCTN 38541912). Ethics committee approval was obtained. Patients underwent both mpUSS and mpMRI independently, each with a positive test defined as a Likert score of >3. Those with either a positive mpUSS or mpMRI, or both, were advised to undergo targeted biopsies. Reporting of each scan was carried out blind to the other and prior to biopsy; patients advised for biopsy were blinded to which test was positive. The order of mpUSS and mpMRI targeting was randomised. Primary outcomes were proportion of positive tests and detection of clinically significant cancer (csPCa) defined as Gleason >4+3 of any length and/or maximum cancer core length of >6mm of any grade [PROMIS definition1]. Results: 306 completed both mpUSS and mpMRI. Agreement in lesion detection between mpUSS and mpMRI was 73.2% (kappa 0.06, p = 0.14). 257 with positive results on mpUSS, mpMRI or both had targeted biopsies. Agreement on detection of csPCa was 91.1% (expected 59.8%, kappa 0.78, p < 0.01). Overall, mpUSS detected 4.3% fewer csPCa than mpMRI (95% CI = [-8.3%, -1.5%]; p = 0.042 [Bonferroni correction]). mpUSS detected 7.2% (6/83) csPCa missed by mpMRI; mpMRI detected 20.5% (17/83) csPCa that mpUSS missed. At a less stringent definition of significant cancer, Gleason grade >3+4 of any length (definition 3), agreement was 89.1% (expected 55.6%, kappa 0.75, p < 0.01) mpUSS detected 5.4% fewer definition 3 cancers than mpMRI overall. mpUSS detected 7% (7/99) definition 3 cancers that mpMRI missed; mpMRI detected 21% (21/99) definition 3 cancers that mpUSS missed. Conclusions: The CADMUS trial shows mpUSS has a diagnostic performance approaching that of mpMRI and significant cancer detection is improved by the use of both scans over mpMRI alone. Clinical trial information: 38541912. [Table: see text]

Prostate cancer (PCa) ranks as the second most frequent cancer and the fifth leading cause of cancer death in men worldwide. Androgen-deprivation therapy is the principal treatment for locally advanced and metastatic disease. Although a majority of patients initially respond well to ADT, most will progress to castration-resistant prostate cancer (CRPC), which contributes to the majority of PCa deaths. Exosomes are small vesicles that contain numerous molecular constituents, including lipids, proteins, RNAs and DNAs, and can mediate cell-cell communications. The aim of this study is to identify plasma exosomal miRNAs correlated with CRPC development, which may serve as a biomarker to monitor disease status and may reveal new role of exosome in CRPC development. Next-generation sequencing (NGS) of plasma exosomal miRNAs was performed in 24 treatment-naive PCa patients and 24 CPRC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate candidate miRNAs in 108 treatment-naive PCa patients and 42 CRPC patients and a group of 38 non-CRPC patients under hormone therapy (treated non-CRPC). To study the miRNA function, hormone-dependent PCa cell line LNCaP was cultured in hormone-depleted media. MiRNA was overexpressed by transient transfection of miRNA mimic. Post transfection, transwell assays and cell viability assays were performed to determine the effect of miRNA on cell migration and proliferation. RNA NGS generated an average of approximately 5-million reads per sample and identified differentially expressed miRNAs. QRT-PCR validation showed six miRNAs were significantly differentially expressed between treatment-naïve PCa and CRPC (p-value Citation Format: Tianyu Guo, Yang Wang, Xueying Mao, Lei Xu, Jacek Marzec, Edwina Burke, Glenda Scandura, Elzbieta Stankiewicz, Caitlin R. Davies, John Hines, Greg Shaw, Jonathan Shamash, Daniel Berney, Prabhakar Rajan, Karen Tipples, Alistair Grey, Yong-jie Lu. Investigation of plasma exosomal miRNA as a biomarker and its potential function in prostate cancer castration resistant development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2580.

Patients with microscopic and macroscopic haematuria undergo a series of investigations to assess the upper and lower urinary tracts. The authors recently demonstrated that urine cytology is an unnecessary expense in the evaluation of haematuria as it slows the patient pathway, is expensive and has a sensitivity of only 41%. The aim of this article is to evaluate the role of the nuclear matrix protein (NMP) 22 urine test as an alternative to urine cytology. The results of 219 patients who completed investigations for haematuria were evaluated: NMP 22 was positive in 26 patients. Cancer was confirmed in 17 of the 219 patients. NMP 22 was negative and cancer excluded in 188 patients. Of the 17 patients with cancer, 12 had a positive NMP 22 test and 5 had a negative NMP 22. Of the 26 patients with a positive NMP 22, 14 were found not to have cancer. This equates to an overall positive predictive value of 46·1%, negative predictive value of 97·4%, sensitivity of 70% and a specificity of 93% which shows that NMP 22 is superior to urine cytology in the investigation of adult haematuria, particularly with a negative predictive value of 97%.

Purpose of review A summary and analysis of the current evidence on the role of multiparametric ultrasound in the diagnosis of clinically significant prostate cancer. Recent findings Earlier work on brightness-mode or Doppler ultrasound did not reveal an adequate diagnostic performance but the addition of contrast-enhanced ultrasound and elastography shows greater promise. There has been an increase in trials on contrast-enhanced ultrasound of late, with and without the use of quantification, such as parametric mapping of contrast uptake. Shear wave elastography offers quantification for this modality also and early work is available on the kilopascal thresholds that may be significant for malignancy. Perhaps the most promising avenue is the combination of the above modalities but to date only one study has considered this. Summary Although there is a paucity of high-quality studies at present, particularly those that combine all the available ultrasound modalities, the performance of ultrasound is seen to approach that of multiparametric MRI in some cases. More work is needed to define a role, if any, for ultrasound in the diagnosis of prostate cancer.