Does true Gleason pattern 3 merit its cancer descriptor?

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted

Additional Value of Dynamic Contrast-enhanced Sequences in Multiparametric Prostate Magnetic Resonance Imaging: Data from the PROMIS Study

Background: Multiparametric magnetic resonance imaging (MP-MRI) is established in the diagnosis of prostate cancer, but the need for enhanced sequences has recently been questioned. / Objective: To assess whether dynamic contrast-enhanced imaging (DCE) improves accuracy over T2 and diffusion sequences. / Design, setting, and participants: PROMIS was a multicentre, multireader trial, with, in this part, 497 biopsy-naïve men undergoing standardised 1.5T MP-MRI using T2, diffusion, and DCE, followed by a detailed transperineal prostate mapping (TPM) biopsy at 5 mm intervals. Likert scores of 1–5 for the presence of a significant tumour were assigned in strict sequence, for (1) T2 + diffusion and then (2) T2 + diffusion + dynamic contrast-enhanced images. / Outcome measurements and statistical analysis: For the primary analysis, the primary PROMIS outcome measure (Gleason score ≥4 + 3 or ≥6 mm maximum cancer length) on TPM was used, and an MRI score of ≥3 was considered positive. / Results and limitations: Sensitivity without and with DCE was 94% and 95%, specificity 37% and 38%, positive predictive value 51% and 51%, and negative predictive value 90% and 91%, respectively (p >  0.05 in each case). The number of patients avoiding biopsy (scoring 1–2) was similar (123/497 vs 121/497, p =  0.8). The number of equivocal scores (3/5) was slightly higher without DCE (32% vs 28% p =  0.031). The proportion of MRI equivocal (3/5) and positive (4–5) cases showing significant tumours were similar (23% and 71% vs 20% and 69%). No cases of dominant Gleason 4 or higher were missed with DCE, compared with a single case with T2 + diffusion-weighted imaging. No attempt was made to correlate lesion location on MRI and histology, which may be considered a limitation. Radiologists were aware of the patient’s prostate-specific antigen. / Conclusions: Contrast adds little when MP-MRI is used to exclude significant prostate cancer

A critical evaluation of visual proportion of Gleason 4 and maximum cancer core length quantified by histopathologists

Gleason score 7 prostate cancer with a higher proportion of pattern 4 (G4) has been linked to genomic heterogeneity and poorer patient outcome. The current assessment of G4 proportion uses estimation by a pathologist, with a higher proportion of G4 more likely to trigger additional imaging and treatment over active surveillance. This estimation method has been shown to have inter-observer variability. Fifteen patients with Prostate Grade Group (GG) 2 (Gleason 3 + 4) and ffteen patients with GG3 (Gleason 4 + 3) disease were selected from the PROMIS study with 192 haematoxylin and eosinstained slides scanned. Two experienced uropathologists assessed the maximum cancer core length (MCCL) and G4 proportion using the current standard method (visual estimation) followed by detailed digital manual annotation of each G4 area and measurement of MCCL (planimetric estimation) using freely available software by the same two experts. We aimed to compare visual estimation of G4 and MCCL to a pathologist-driven digital measurement. We show that the visual and digital MCC

False Positive Multiparametric Magnetic Resonance Imaging Phenotypes in the Biopsy-naïve Prostate: Are They Distinct from Significant Cancer-associated Lesions? Lessons from PROMIS.

Background False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer.Objective To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM).Design, setting, and participants PROMIS participants (n=235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3+4 of any length and/or maximum cancer core length ≥4mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4+3 of any length and/or maximum cancer core length ≥6mm of any grade).Outcome measurements and statistical analysis Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics.Results and limitations Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p2PSA density and index lesion ADC were significant predictors of definition 1/2 disease in a logistic regression model (mean cross-validated area under the receiver-operator characteristic curve: 0.77 [95% confidence interval: 0.67-0.87]).Conclusions Significant cancer-associated MRI lesions in biopsy-naïve men have clinical-radiological differences, with lesions seen in prostates without significant disease. MRI-calculated PSA density and ADC could predict significant cancer in those with indeterminate MRI phenotypes.Patient summary Magnetic resonance imaging (MRI) lesions that mimic prostate cancer but are, in fact, benign prompt unnecessary biopsies in thousands of men with raised prostate-specific antigen. In this study we found that, on closer look, such false positive lesions have different features from cancerous ones. This means that doctors could potentially develop better tools to identify cancer on MRI and spare some patients from unnecessary biopsies