Abstract
BackgroundWhile the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5. Furthermore, no study has “quantified” the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy.MethodsWe reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. The primary endpoint was biochemical recurrence-free survival, defined as two consecutive prostate-specific antigen measurements ≥0.2 ng/ml after surgery. The individual quantitative risk score (IQRS) of each amount (primary/secondary/tertiary) of each Gleason pattern (3/4/5) was calculated using the Cox regression model. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was also assessed.ResultsDuring a median follow-up of 45 months, 229 of 1022 (22.4%) patients developed biochemical recurrence. The IQRS of each Gleason pattern was as follows: primary 5, 1.81 points (hazard ratio [HR] 6.13); secondary 5, 1.37 points (HR 3.92); tertiary 5, 0.87 points (HR 2.39); primary 4, 1.07 points (HR 2.91); secondary 4, 0.79 points (HR 2.21); and any Gleason pattern 3, 0 points (HR 1). Based on the IQRS, the mGGG model was developed, which classified patients into the following five groups: I (3 + 3 or less); II (3 + 4); III (4 + 3); IV (3 + 4 + t5, 4 + 3 + t5, 3 + 5, 5 + 3, and 4 + 4); V (4 + 4 + t5, 4 + 5, 5 + 4, and 5 + 5). The c-index for biochemical recurrence-free survival was significantly improved from 0.655 of the original GGG model to 0.672 of the mGGG model (P < 0.05). In the robustness analysis, the c-index for salvage treatment-free survival was also significantly improved from 0.619 of the original GGG model to 0.638 of the mGGG model (P < 0.05).ConclusionsThe quantitative risk of tertiary (< 5%) Gleason pattern 5 is slightly higher than that of secondary (5–50%) Gleason pattern 4. Our newly developed mGGG model more accurately predicts outcomes after radical prostatectomy than the original GGG model.
Highlights
While the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5
The prognostic value of GGG has been confirmed in several settings [19,20,21], it does not incorporate the concept of tertiary Gleason pattern 5
A recent study reported that integrating tertiary Gleason pattern 5 into GGG improved the accuracy of predicting the patient’s outcome after radical prostatectomy [16]
Summary
We reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was assessed. We reviewed 1167 patients with PC who underwent radical prostatectomy at The University of Tokyo Hospital between 2005 and 2017. We excluded 32 patients who had received neoadjuvant androgen deprivation therapy (ADT) to guarantee an accurate pathological diagnosis. We excluded 113 patients who received adjuvant treatment after surgery (radiotherapy, n = 14; ADT, n = 64; and both, n = 35) to assess the pure oncological outcome of surgery alone. All prostatectomy specimens were pathologically reviewed according to the 2005 ISUP Consensus Conference on Gleason Grading of Prostatic Carcinoma [3]
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