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.

Mainstreamed genetic testing in ovarian cancer: patient experience of the testing process.

OBJECTIVE: Pathogenic BRCA variants account for 5.8-24.8% of ovarian cancers. The identification of such a variant can have a significant impact on the affected individual and their relatives, determining eligibility for targeted therapies, predicting treatment response, and granting access to disease prevention strategies. Cancer services are responding to the increased demand for genetic testing with the introduction of mainstreamed genetic testing via oncology clinics. This study aimed to evaluate patient experience of the mainstreamed genetic testing pathway at a tertiary referral center in London, UK. METHODS: Study participants were patients diagnosed with high-grade non-mucinous ovarian cancer, tested via a mainstreamed genetic testing pathway at the tertiary referral center between February 2015 and June 2017. Eligible participants were invited to complete the retrospective study questionnaire. Five quantitative measures with additional free-text items were used to evaluate the patient experience of mainstreamed genetic testing. RESULTS: The tertiary referral center tested 170 ovarian cancer patients. Twenty-three pathogenic BRCA mutations were identified (23/170, 13.5%). One-hundred and six patients (106/170, 62.4%) met the study inclusion criteria. Twenty-nine of those invited to participate (29/106, 27.4%) returned the retrospective study questionnaire. Pathogenic BRCA1/2 variants were identified within four respondents (4/29, 13.8%). Motivations for genetic testing related to improved medical management, and the ability to provide relatives with genetic information. Participants did not appear to be adversely affected by result disclosure post-mainstreamed genetic testing. Two individuals with a pathogenic variant reported that the support provided by the tertiary referral center post-result disclosure could have been improved. CONCLUSION: Results of the current study support further psychosocial research into the expansion of the mainstreamed genetic testing pathway. The results, although promising, have also highlighted the importance of genetic awareness within the multi-disciplinary team and the provision of timely psychological support from genetic specialists.