Adam I Cole1, Todd M Morgan1, Daniel E Spratt2, Ganesh S Palapattu3, Chang He1, Scott A Tomlins4, Alon Z Weizer3, Felix Y Feng2, Angela Wu5, Javed Siddiqui5, Arul M Chinnaiyan4, Jeffrey S Montgomery1, Lakshmi P Kunju6, David C Miller1, Brent K Hollenbeck1, John T Wei1, Rohit Mehra7. 1. Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan. 2. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan. 3. Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan. 4. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan. 5. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan. 6. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan. 7. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan. Electronic address: mrohit@med.umich.edu.
Abstract
PURPOSE: The importance of primary Gleason grade among men with Gleason score 7 disease has been well-defined. However, this dichotomization may oversimplify the continuous spectrum of absolute percent Gleason grade 4 disease (G4%). In this study we report the prognostic value of G4% in cancer related outcomes of men undergoing radical prostatectomy. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for clinically localized Gleason 6-8 prostate cancer from 2005 to 2013 were included in the study. G4% was determined as biopsy tumor length containing Gleason pattern 4/total tumor length, which performed better than alternative quantifications of pattern 4 involvement. G4% was correlated with time to biochemical recurrence and presence of adverse radical prostatectomy pathology, defined as primary Gleason 4 or pT3 or greater, by multivariable Cox and logistic regressions. RESULTS: Of 1,691 patients 517 (30.6%) had adverse pathological features and 86 (5.6%) experienced biochemical recurrence. On multivariable analyses G4% was a significant predictor of adverse pathology (OR 1.04, 95% CI 1.03-1.05) and time to biochemical recurrence (HR 1.02, CI 1.01-1.03). G4% was also a significant independent predictor of adverse pathology in subsets of patients with Gleason score 7 (OR 1.05, 95% CI 1.03-1.06), 3+4 (OR 1.06, 95% CI 1.04-1.08) and 4+3 cancer (OR 1.05, 95% CI 1.03-1.06). We found a significantly increased risk of adverse pathology at potentially meaningful G4% thresholds (1% to 10% vs 20% to 30%). CONCLUSIONS: The incremental percentage of Gleason grade 4 disease in biopsy specimens is an important predictor of adverse pathology and biochemical recurrence across the entire range of G4% disease. Accounting for G4% can improve risk assessment even among those patients with Gleason 3+4 or 4+3 cancer and may help inform patient counseling.
PURPOSE: The importance of primary Gleason grade among men with Gleason score 7 disease has been well-defined. However, this dichotomization may oversimplify the continuous spectrum of absolute percent Gleason grade 4 disease (G4%). In this study we report the prognostic value of G4% in cancer related outcomes of men undergoing radical prostatectomy. MATERIALS AND METHODS:Patients who underwent radical prostatectomy for clinically localized Gleason 6-8 prostate cancer from 2005 to 2013 were included in the study. G4% was determined as biopsy tumor length containing Gleason pattern 4/total tumor length, which performed better than alternative quantifications of pattern 4 involvement. G4% was correlated with time to biochemical recurrence and presence of adverse radical prostatectomy pathology, defined as primary Gleason 4 or pT3 or greater, by multivariable Cox and logistic regressions. RESULTS: Of 1,691 patients 517 (30.6%) had adverse pathological features and 86 (5.6%) experienced biochemical recurrence. On multivariable analyses G4% was a significant predictor of adverse pathology (OR 1.04, 95% CI 1.03-1.05) and time to biochemical recurrence (HR 1.02, CI 1.01-1.03). G4% was also a significant independent predictor of adverse pathology in subsets of patients with Gleason score 7 (OR 1.05, 95% CI 1.03-1.06), 3+4 (OR 1.06, 95% CI 1.04-1.08) and 4+3 cancer (OR 1.05, 95% CI 1.03-1.06). We found a significantly increased risk of adverse pathology at potentially meaningful G4% thresholds (1% to 10% vs 20% to 30%). CONCLUSIONS: The incremental percentage of Gleason grade 4 disease in biopsy specimens is an important predictor of adverse pathology and biochemical recurrence across the entire range of G4% disease. Accounting for G4% can improve risk assessment even among those patients with Gleason 3+4 or 4+3 cancer and may help inform patient counseling.
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