Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography: The IP1-PROSTAGRAM Study

Abstract

Importance: 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.

Objective: 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.

Interventions: 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.

Results: 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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Eldred-Evans reported receiving grants from the BMA Foundation for Medical Research, The Urology Foundation, and the Royal College of Surgeons of England during the conduct of the study; grants from Imperial Health Charity outside the submitted work; and equipment support from SuperSonic Inc. Dr Connor reported receiving grants from Wellcome Trust and University College London Hospitals Charity outside the submitted work. Dr Ahmed reported receiving grants from Wellcome Trust, the BMA Foundation for Medical Research, and The Urology Foundation during the conduct of the study and grants and personal fees from Sophiris Biocorp, Sonacare Inc, and Boston Scientific (previously Galil and BTG) and grants from Trod Medical, Prostate Cancer UK Charity, MRC (UK), Cancer Research UK, and Imperial Health Charity outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Screening, Recruitment, and Flow of Participants

MRI indicates magnetic resonance imaging; PSA, prostate-specific antigen; UTI, urinary tract infection.

Figure 2.. Comparison of Detected Clinically Significant Cancers by Each Screening Test According to Magnetic Resonance Imaging (MRI) and Ultrasonography (US) Threshold

A, Clinically significant cancer is defined as a Gleason score of 3+4 or higher (International Society of Urological Pathology score ≥2). Positive test results are defined as a prostate-specific antigen (PSA) level of 3 ng/mL or higher, an MRI score of 3 to 5, and a US score of 3 to 5. The PSA levels for the 8 men with MRI scores of 3 to 5 and a PSA level less than 3 ng/mL (to convert to micrograms per liter, multiply by 1) are provided in eTable 3 in the Supplement. B, Clinically significant cancer is defined as a Gleason score of 3+4 or higher (International Society of Urological Pathology score ≥2). TB indicates targeted biopsy; SB, systematic biopsy.