What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort
Authors: Joseph M. Norris, Lina M. Carmona Echeverria, Simon R.J. Bott, Louise C. Brown, Nick Burns-Cox, Tim Dudderidge, Ahmed El-Shater Bosaily, Eleni Frangou, Alex Freeman, Maneesh Ghei, Alastair Henderson, Richard G. Hindley, Richard S. Kaplan, Alex Kirkham, Robert Oldroyd, Chris Parker, Raj Persad, Shonit Punwani, Derek J. Rosario, Iqbal S. Shergill, Vasilis Stavrinides, Mathias Winkler, Hayley C. Whitaker, Hashim U. Ahmed, Mark Emberton
Journal: European Urology (2020)

All risk stratification strategies in cancer overlook a spectrum of disease. The Prostate MR Imaging Study (PROMIS) provides a unique opportunity to explore cancers that are overlooked by multiparametric magnetic resonance imaging (mpMRI).To summarise attributes of cancers that are systematically overlooked by mpMRI.PROMIS tested performance of mpMRI and transrectal ultrasonography (TRUS)-guided biopsy, using 5 mm template mapping (TPM) biopsy as the reference standard.Outcomes were overall and maximum Gleason scores, maximum cancer core length (MCCL), and prostate-specific antigen density (PSAD). Cancer attributes were compared between cancers that were overlooked and those that were detected.Of men with cancer, 7% (17/230; 95% confidence interval [CI] 4.4-12%) had significant disease overlooked by mpMRI according to definition 1 (Gleason ≥ 4 + 3 of any length or MCCL ≥ 6 mm of any grade) and 13% (44/331; 95% CI 9.8-17%) according to definition 2 (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm). In comparison, TRUS-guided biopsy overlooked 52% (119/230; 95% CI 45-58%) of significant disease by definition 1 and 40% (132/331; 95% CI 35-45%) by definition 2. Prostate cancers undetected by mpMRI had significantly lower overall and maximum Gleason scores (p = 0.0007; p < 0.0001) and shorter MCCL (median difference: 3 mm [5 vs 8 mm], p < 0.0001; 95% CI 1-3) than cancers that were detected. No tumours with overall Gleason score > 3 + 4 (Gleason Grade Groups 3-5; 95% CI 0-6.4%) or maximum Gleason score > 4 + 3 (Gleason Grade Groups 4-5; 95% CI 0-8.0%) on TPM biopsy were undetected by mpMRI. Application of a PSAD threshold of 0.15 reduced the proportion of men with undetected cancer to 5% (12/230; 95% CI 2.7-8.9%) for definition 1 and 9% (30/331; 95% CI 6.2-13%) for definition 2. Application of a PSAD threshold of 0.10 reduced the proportion of men with undetected disease to 3% (6/230; 95% CI 1.0-5.6%) for definition 1 cancer and to 3% (11/331; 95% CI 1.7-5.9%) for definition 2 cancer. Limitations were post hoc analysis and uncertain significance of undetected lesions.Overall, a small proportion of cancers are overlooked by mpMRI, with estimates ranging from 4.4% (lower boundary of 95% CI for definition 1) to 17% (upper boundary of 95% CI for definition 2). Prostate cancers undetected by mpMRI are of lower grade and shorter length than cancers that are detected.Prostate cancers that are undetected by magnetic resonance imaging (MRI) are smaller and less aggressive than those that are detected, and none of the most aggressive cancers are overlooked by MRI.