Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

Objectives: To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing. Patients and Methods: Newly-diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi-centre randomised, double-blind, placebo-controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12-month disease re-assessment (imaging/biochemical/histological), and 12-month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging-Reporting and Data System (PI-RADS) 4/5 lesion(s) on multi-parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length. Results: Of 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve-month disease progression rate was 43.3%. Assessable 12-month treatment adherence in non-progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug-attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms. Conclusion: Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers.

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study.

BACKGROUND: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer. METHODS: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm2 or 2000 s/mm2 and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed. FINDINGS: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity. INTERPRETATION: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone. FUNDING: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity.

Can transrectal prostate ultrasound compete with multiparametric MRI in the detection of clinically significant prostate cancer?

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.

Diagnostic accuracy of magnetic resonance imaging (MRI) prostate imaging reporting and data system (PI-RADS) scoring in a transperineal prostate biopsy setting.

OBJECTIVES: To determine the sensitivity and specificity of multiparametric magnetic resonance imaging (mpMRI) for significant prostate cancer with transperineal sector biopsy (TPSB) as the reference standard. PATIENTS AND METHODS: The study included consecutive patients who presented for TPSB between July 2012 and November 2013 after mpMRI (T2- and diffusion-weighted images, 1.5 Tesla scanner, 8-channel body coil). A specialist uro-radiologist, blinded to clinical details, assigned qualitative prostate imaging reporting and data system (PI-RADS) scores on a Likert-type scale, denoting the likelihood of significant prostate cancer as follows: 1, highly unlikely; 3, equivocal; and 5, highly likely. TPSBs sampled 24-40 cores (depending on prostate size) per patient. Significant prostate cancer was defined as the presence of Gleason pattern 4 or cancer core length ≥6 mm. RESULTS: A total of 201 patients were included in the analysis. Indications were: a previous negative transrectal biopsy with continued suspicion of prostate cancer (n = 103); primary biopsy (n = 83); and active surveillance (n = 15). Patients' mean (±sd) age, prostate-specific antigen and prostate volumes were 65 (±7) years, 12.8 (±12.4) ng/mL and 62 (±36) mL, respectively. Overall, biopsies were benign, clinically insignificant and clinically significant in 124 (62%), 20 (10%) and 57 (28%) patients, respectively. Two of 88 men with a PI-RADS score of 1 or 2 had significant prostate cancer, giving a sensitivity of 97% (95% confidence interval [CI] 87-99) and a specificity of 60% (95% CI 51-68) at this threshold. Receiver-operator curve analysis gave an area under the curve of 0.89 (95% CI 0.82-0.92). The negative predictive value of a PI-RADS score of ≤2 for clinically significant prostate cancer was 97.7% CONCLUSION: We found that PI-RADS scoring performs well as a predictor for biopsy outcome and could be used in the decision-making process for prostate biopsy.

Tamsulosin MR and OCAS (modified release and oral controlled absorption system): current therapeutic uses.

BACKGROUND: Although tamsulosin is mainly used to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia, with better understanding of functional anatomy and distribution of alpha(1) receptors, it is also indicated in other conditions of genito-urinary tract in both men and women. OBJECTIVE: To detail the therapeutic use and clinical effects of tamsulosin. METHODS: The scope of the review was related to tamsulosin and its therapeutic application in conditions of genitourinary tract. Publications were searched from Pubmed and Medline from 1975 to 2007 using the search words tamsulosin, lower urinary tract symptoms, alpha receptors and blockers. CONCLUSIONS: The management of benign prostatic hyperplasia was transurethral resection of prostate until simpler and alternative treatments were tried in the last two decades, particularly alpha(1) adrenoceptor-blocking agents. Tamsulosin is a potent, third-generation selective alpha(1A) adrenoceptor-blocking agent.