An ultrasound scan was able to diagnose most prostate cancer cases with good accuracy in a clinical trial involving 370 men, reports a study in Lancet Oncology from Imperial College London, University College London and Imperial College Healthcare NHS Trust.
The scans missed only 4.3% more clinically important prostate cancer cases – cancer that should be treated rather than monitored – compared with considerably more expensive and time-consuming magnetic resonance imaging (MRI) scans currently used to detect prostate cancer.
The team suggests that an ultrasound scan should be used as a first test in a community healthcare setting and in low- and middle-income countries that do not have easy access to high quality MRI scans. They say it could be used in combination with current MRI scans to maximise cancer detection.
Professor Hashim Ahmed, lead author and Chair of Urology at Imperial College London, said: “Prostate cancer is the most commonly diagnosed cancer in the UK. One in six men will be diagnosed with this in their lifetimes and that figure is expected to rise.
“MRI scans are one of the tests we use to diagnose prostate cancer. Although effective they are expensive, take up to 40 minutes to perform, and are not easily available to all. Also, some patients are unable to have MRI scans, such as those with hip replacements or claustrophobia fears. As cancer waiting lists build as a result of the COVID-19 pandemic, there is a real need to find more efficient and cheaper tests to diagnose prostate cancer.
“Our study is the first to show that a special type of ultrasound scan can be used as a potential test to detect clinically significant cases of prostate cancer. The scan will detect most cases of prostate cancer with good accuracy, although MRI scans are slightly better.
“We believe that this test can be used in low- and middle-income settings where access to expensive MRI equipment is difficult and cases of prostate cancer are growing.”
Prostate cancer is the most common cancer in men in the UK with around 52,300 new cases diagnosed each year. It develops when cells in the prostate grow in an uncontrolled way. Prostate cancer develops slowly and symptoms, such as blood in the urine, do not appear until the disease has developed. It usually affects men over 50 and often men with a family history of the disease. Black men are disproportionately affected by the disease, and deaths from prostate cancer have now overtaken those from breast cancer.
One of the main methods to diagnose prostate cancer is a special type of Magnetic Resonance Imaging (MRI) scan called a Multi-Parametric MRI (mpMRI) scan, which helps doctors see if there is any cancer inside the prostate and how quickly the cancer is likely to grow. However, the scan takes 40 minutes and is expensive.
The latest study looked at the use of a different kind of imaging called multiparametric ultrasound (mpUSS), which uses sound waves to look at the prostate. The test involves a probe, called a transducer, to make images of the prostate. It is placed into the rectum and sends out sound waves that bounce off organs and other structures. These are then made into pictures of the organs.
The doctor doing the test also uses extra special types of ultrasound imaging that look at how stiff the tissue is and how much blood supply tissue has. These are called elastography, doppler and contrast-enhancement, with microbubbles. As cancers are denser and have greater blood supply, they show up more clearly.
Although mpUSS is more widely available than mpMRI there has been no large-scale studies to validate its effectiveness as a test to detect prostate cancer cases.
In this latest trial, called cancer diagnosis by multiparametric ultrasound of the prostate (CADMUS), the team recruited 370 men at risk of prostate cancer. They were identified after initial tests such as a prostate-specific antigen (PSA) test, a blood test to help detect prostate cancer, and/or an abnormal digital rectal examination (which examines the lower rectum, pelvis, and lower belly).
The study took place at seven hospitals in the UK including lead site Charing Cross Hospital, part of Imperial College Healthcare NHS Trust, between March 2016 and November 2019.
The men were given both mpUSS and mpMRI scans at separate visits. This was then followed by biopsies, involving using thin needles to take small samples of tissue from the prostate to analyse under a microscope to check cancer, for 257 patients who had a positive mpUSS or mpMRI test result. The team then compared the results.
Cancer was detected in 133 men, with 83 of them diagnosed with clinically significant cancer.
Individually, mpUSS detected 66 cases of clinically significant cancer compared to mpMRI, which detected 77 cases. Although mpUSS detected 4.3% fewer clinically-important prostate cancers compared with mpMRI, the researchers said this method would lead to 11.1% more patients being biopsied. This was because the mpUSS sometimes showed up abnormal areas even though there was no cancer.
The researchers believe the test can be used as an alternative to mpMRI as a first test for patients at risk of prostate cancer, particularly where mpMRI cannot be carried out. Both imaging tests missed clinically-important cancers detected by the other, so using both would increase the detection of clinically-important prostate cancers compared to using each test alone.
First author Dr Alistair Grey (UCL Division of Surgery & Interventional Science), said: “Our results provide an accurate test for prostate cancer in patients who were previously without one, using a scan that’s cheap and easy to conduct.”
Study details
Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study
Alistair Grey, Rebecca Scott, Bina Shah, Peter Acher, Sidath Liyanage, Menelaos Pavlou, Rumana Omar, Frank Chinegwundoh, Prasad Patki, Taimur Shah, Sami Hamid, Maneesh Ghei, Kayleigh Gilbert, Diane Campbell, Chris Brew-Graves, Nimalan Arumainayagam, Alex Chapman, Laura McLeavy, Angeliki Karatziou, Zayneb Alsaadi, Tom Collins, Alex Freeman, David Eldred-Evans, Mariana Bertoncelli-Tanaka, Henry Tam, Navin Ramachandran, Sanjeev Madaan, Mathias Winkler, Manit Arya, Mark Emberton, Hashim Ahmed.
Published in The Lancet Oncology on 1 March 2022
Summary
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.
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