MRI improves detection of clinically significant prostate cancer — IP1-PROSTAGRAM study
MRI improved detection of clinically significant prostate cancer without increasing overdiagnosis compared with PSA testing, according to a prospective, population-based, blinded cohort study. The IP1-PROSTAGRAM study also showed ultrasonography did not improve prostate cancer detection in the general population compared with PSA testing alone.
“The PSA threshold was set at 3 ng/mL or greater to denote a screen-positive result in line with previous screening trials,” Dr David Eldred-Evans, senior clinical research fellow at Imperial Prostate, Imperial College London, is quoted in Healio as saying. “Our findings re-emphasise that when interpreting PSA, it is not a dichotomous test, and it is more useful as a continuous variable reflecting a continuum of prostate cancer risk. In IP1-PROSTAGRAM, significant prostate cancer was identified by MRI in men with PSA as low as 0.69 ng/mL.”
Eldred-Evans and colleagues evaluated whether a short, non-contrast MRI protocol – which has an acquisition time of about 15 minutes – or transrectal ultrasonography using an ultrafast scanner (Aixplorer, SuperSonic Imagine) could overcome some of the limitations of PSA testing, which can lead to under- and overdiagnosis, they wrote. Also, identification of a reliable testing method could pave the way for a national prostate cancer screening programme, Eldred-Evans said.
“Image-based screening tests have been successfully adopted in other cancers, such as mammograms for breast cancer and CT for lung cancer,” he said. “In prostate cancer, there have been many previous studies evaluating MRI or ultrasound as tests in secondary care for men with a suspicion of prostate cancer; however, no studies have considered this combination of imaging tests for screening. Our aim was to understand whether fast MRI or ultrasound could be the basis for a new method of a screening program for prostate cancer.”
Healio reports that the analysis included 408 men aged 50 to 69 years (38% white, 32.4% Black, 23% Asian) enrolled between October 2018 and May 2019 at seven primary care practices in the UK. The men had a life expectancy of at least 10 years; no PSA tests or prostate MRI in the previous 2 years; no urinary infection or prostatitis in the previous 6 months; and no history of prostate biopsy, prostate cancer or any contraindication to MRI.
The men underwent prostate cancer screening with a PSA test, MRI and ultrasonography and, if any results appeared positive on a 5-point scale, they underwent a systematic 12-core biopsy. Men with positive MRI or ultrasound results also underwent additional image fusion-targeted biopsy.
The proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as 3 ng/mL) served as the study’s main outcome. When using the 3-to-5 score threshold, results showed the proportion of men with positive results appeared higher with MRI (17.7%; 95% CI, 14.3-21.8) and ultrasonography (23.7%; 95% CI, 19.8-28.1) than with PSA testing (9.9%; 95% CI, 7.3-13.2; P < .001 for both).
Using the 4-to-5 score threshold, 10.6% (95% CI, 7.9-14) of men had positive MRI and 12.8% (95% CI, 9.9-16.5) had positive ultrasonography, which was not significantly different than the 9.9% of men positive per PSA testing.
Combined targeted and systematic biopsy identified 37 prostate cancers, 17 of which were clinically significant.
Overall, PSA testing detected seven of the clinically significant cancers, whereas an MRI detected 11 (4-5 threshold) to 14 (3-5 threshold), and ultrasonography detected four (4-5 threshold) to nine (3-5 threshold).
Of the 20 clinically insignificant prostate cancers detected on biopsy, PSA testing detected six, MRI detected five (4-5 threshold) to seven (3-5 threshold), and ultrasonography detected seven (4-5 threshold) to 13 (3-5 threshold).
These data suggest MRI testing detected two times as many significant cancers as PSA testing alone. Moreover, using the 4-to-5 threshold for MRI may improve the detection of clinically significant prostate cancer without leading to unnecessary biopsy or overdiagnosis, according to the researchers.
“A fast MRI appears to have favourable performance characteristics as a new screening test for prostate cancer,” Eldred-Evans told Healio. “This finding needs further evaluation in subsequent studies.
“The ultrasound did not perform as well as in previous secondary care populations,” Eldred-Evans added. “(This is possibly because) we did not include contrast in the scanning protocol to keep the test non-invasive and/or the significant cancers being detected were low volume. Meanwhile, a fast MRI scan … was able to identify a high number of aggressive cancers without increasing the number of men needing a biopsy compared with PSA.”
This study suggests MRI “will play an important role” in reducing the morbidity and mortality of prostate cancer, according to an editorial accompanying the study by Dr Susanna I Lee, chief of women’s imaging, and Dr Aileen O’Shea, clinical fellow in radiology, both of Massachusetts General Hospital.
“Their findings clearly point to prostate MRI as a promising screening test,” they wrote. “Future trials should be designed to include MRI in the prostate cancer screening strategy with image acquisition and interpretation protocols that are widely accessible, well-tolerated and readily generalisable.
“In the long run, if successful, prostate MRI will be able to join mammography and low-dose CT of the thorax as an imaging screening test that saves lives and improves the general health of the population,” they added.
Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography: The IP1-PROSTAGRAM Study
David Eldred-Evans; Paula Burak; Martin J Connor; Emily Day; Martin Evans; Francesca Fiorentino; Martin Gammon; Feargus Hosking-Jervis; Natalia Klimowska-Nassar; William McGuire; Anwar R Padhani; A Toby Prevost; Derek Price; Heminder Sokhi; Henry Tam; Mathias Winkler; Hashim U Ahmed
Published in JAMA Oncology on 11 February 2021
Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations.
To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer.
Design, Setting, and Participants
This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019.
All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion–targeted biopsies were performed if the MRI or ultrasonography results were positive.
Main Outcomes and Measures
The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher.
A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases.
Conclusions and Relevance
In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.