Abstract
Percentage Gleason pattern 4, invasive cribriform and/or intraductal carcinoma (IC/IDC) and minor pattern 5 are recognized as independent parameters for prostate cancer outcome, but are not incorporated in current grade groups (GGs). Two proof-of-principle studies have proposed alternative grading schemes based on percentage Gleason pattern 4/5 (integrated quantitative Gleason score; IQ-Gleason) and IC/IDC presence (cribriform grade; cGrade). Our objective was to compare the performance of GG, IQ-Gleason and cGrade for predicting biochemical recurrence and metastasis after radical prostatectomy (RP). RP specimens of 1064 patients were pathologically reviewed and graded according to the three schemes. Discriminative power for prediction of biochemical recurrence-free (BCRFS) and metastasis-free (MFS) survival was compared using Harrell’s c-index. The GG distribution at RP was 207 (19.4%) GG1, 472 (44.4%) GG2, 126 (11.8%) GG3, 140 (13.2%) GG4 and 119 (11.2%) GG5. Grading according to 5-tier IQ-Gleason and cGrade systems led to categorical shifts in 49.8% and 29.7% of cases, respectively. Continuous IQ-Gleason had the best performance for predicting BCRFS (c-index 0.743, 95% confidence interval (CI) 0.715–0.771), followed by cGrade (c-index 0.738, 95%CI 0.712–0.759), 5-tier categorical IQ-Gleason (c-index 0.723, 95%CI 0.695–0.750) and GG (c-index 0.718, 95%CI 0.691–0.744). Continuous IQ-Gleason (c-index 0.834, 95%CI 0.802–0.863) and cGrade (c-index 0.834, 95%CI 0.808–0.866) both had better predictive value for MFS than categorical IQ-Gleason (c-index 0.823, 95%CI 0.788–0.857) and GG (c-index 0.806, 95%CI 0.777–0.839). In conclusion, the performance of prostate cancer grading can be improved by alternative grading schemes incorporating percent Gleason pattern 4/5 and IC/IDC.
Highlights
The Gleason grading system is the cornerstone of risk assessment and prediction of clinical outcome in prostate cancer (PCa) patients
Patients who had undergone radical prostatectomy (RP) for prostatic adenocarcinoma at three medical centres in The Netherlands between 2000 and 2017 were included in this study; 854 patients were operated at Erasmus MC, University Medical Centre, Rotterdam; 96 at Leiden University Medical Centre (LUMC), Leiden; and 137 at Antoni van Leeuwenhoek Hospital, The Netherlands Cancer Institute (NKI), Amsterdam
Gleason pattern 4 percentage, presence of invasive cribriform and/or intraductal carcinoma (IC/IDC) and minor/tertiary Gleason patterns have been well acknowledged as independent prognostic features of prostate cancer
Summary
The Gleason grading system is the cornerstone of risk assessment and prediction of clinical outcome in prostate cancer (PCa) patients. The clinical relevance of pathological parameters such as Gleason pattern 4 quantity, presence of invasive cribriform and intraductal (IDC) carcinoma, and minor/tertiary Gleason patterns has been well acknowledged [1,2,3, 7, 8, 12, 15]. The risk of postoperative biochemical recurrence is increasing with incremental Gleason 4 pattern quantity and presence of minor Gleason pattern 5 [1, 2, 10, 15]. Invasive cribriform and/or intraductal carcinoma (IC/IDC) has been associated with biochemical recurrence, metastatic disease and disease-specific survival [3, 7, 8, 12]. The ISUP and GUPS both recommend including these specific features in pathology reports [4, 19]
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