Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study

Abstract

Background The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods From January 2014 to January 2018, 100 men aged 50–63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss’ kappa (κ) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD ±10%, range 62–96%), and mean specificity 60% (SD ±22%, range 27–82%). For csPCa (Gleason Grade 2–5) MRI was equally sensitive (mean 82%, SD ±9%, range 67–97%) but less specific (mean 47%, SD ±20%, range 21–75%). Interreader agreement for any lesion was fair (κ 0.40) and for PI-RADS 4–5 lesions it was moderate (κ 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.

Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study

“…Similar to our findings on MRI-related inter-reader variation [ 8 ], the extremes of the scale seem to be consistently reported, while the intermediate zone with borderline cases is challenging. We found the highest consensus with GG0 (100.0%) and GG5 (85.7%) and lower consensus within GG3 (25.0%) and GG2 (68.0%) cancer.…”

“…The aim was to evaluate interreader variability in MRI and MRI-targeted biopsy. All 100 men were included in the previously reported study of interreader variability in MRI, and the cohort selection and patient demographics have been reported earlier [ 8 ]. For this study, 91 men had undergone MRI before diagnostic biopsies, whereas for 9 men, the MRI was used post-biopsy in cancer staging before definitive treatment.…”

Clinical Trial Protocol: Developing an Image Classification Algorithm for Prostate Cancer Diagnosis on Three-dimensional Multiparametric Transrectal Ultrasound

“…However, the widespread integration of MRI in early detection also poses challenges concerning availability and quality [8] . First, although MRI has improved patient selection for prostate biopsy, the positive predictive value (PPV) of MRI remains limited, resulting in a substantial number of patients undergoing unnecessary biopsies [1] , [2] , [3] , [4] , [9] , [10] , [11] . Furthermore, in studies reporting high sensitivity, such as the 4M and PRECISION trials, MRI findings are assessed by multiple experienced uroradiologists from high-volume centers [2] , [3] , [4] , [9] .…”

An optimized prostate biopsy strategy in patients with a unilateral lesion on prostate magnetic resonance imaging avoids unnecessary biopsies

“… 20 MRI is also subject to considerable interobserver variability, with kappa values (0.31–0.60) reaching only fair to moderate agreement for experienced radiologists. 21 – 23 Biopsy operator experience is a significant predictor for the detection of PCa at biopsy, reaching odds ratios of 2.40. 24 Finally, the targeting technique used during TBx can impact the accuracy.…”