An Evaluation of Screening Pathways Using a Combination of Magnetic Resonance Imaging and Prostate-specific Antigen: Results from the IP1-PROSTAGRAM Study

Abstract

BackgroundThe use of prostate-specific antigen (PSA) testing to screen for prostate cancer has been fraught with under- and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) might detect more grade group ≥2 cancers with similar rates of biopsy. ObjectiveTo evaluate strategies that combined PSA and MRI to select men based in the community for a prostate biopsy. Design, setting, and participantsIP1-PROSTAGRAM was a prospective, population-based, paired cohort study of 408 men aged 50–69 yr conducted at seven UK primary care practice and two imaging centres (from October 10, 2018 to May 15, 2019). InterventionAll participants underwent screening with a PSA test, MRI (T2-weighted and diffusion), and transrectal ultrasound (b-mode and elastography). If any test was screen positive, a systematic 12-core biopsy was performed. Additional image-fusion targeted biopsies were taken if the MRI or ultrasound was positive. Outcome measurements and statistical analysisWe conducted an analysis, set out in the statistical plan a priori, comparing 13 different pathways including PSA-alone, MRI-alone, and a range of PSA thresholds and MRI scores. The performance of each pathway was evaluated focusing on the trade-offs between biopsy referral rates and detection of grade group ≥2 cancers. A targeted biopsy was performed only where the PROSTAGRAM MRI showed a lesion score of 3, 4, or 5. Results and limitationsThe standard PSA pathway (PSA ≥3 ng/ml + systematic biopsy) would lead to 10% of men being referred for a biopsy and a 1.0% detection rate of grade group ≥2 cancers. Pathways that relied on MRI alone set at a threshold score of 3 for a biopsy led to higher biopsy rates, but with benefit of high cancer detection rates. The pathway that combined an initial low PSA threshold (≥1.0 ng/ml) and MRI score ≥4 accurately identified a high rate of grade group ≥2 cancers (2.5%, 95% confidence interval 1.3–4.6) while recommending fewer patients for a biopsy (7.1%, 95% confidence interval 4.9–10.2). The results are pertinent to only one screening round, the impact of repeat screening rounds is not evaluated, and the required MRI capacity is currently lacking. ConclusionsOur results highlight the trade-off that exists between reducing excessive numbers of biopsies and maintaining grade group ≥2 cancer detection rates. A pathway that combines PSA ≥1 ng/ml and MRI score ≥4 maintains the detection of grade group ≥2 cancers while recommending fewer men for biopsies and would be the preferred strategy to evaluate in future studies at the first screening round. Patient summaryThe IP1-PROSTAGRAM study shows that PROSTAGRAM magnetic resonance imaging in men with a prostate-specific antigen level of ≥1.0 ng/ml could be a promising pathway to evaluate in future screening trials.