Predictive value of primary Gleason pattern 4 in patients with Gleason score 7 tumours treated with radical prostatectomy

OBJECTIVE: To examine whether Gleason score (GS) 3 + 4 and 4 + 3 cancers at radical prostatectomy behave differently and whether this behaviour is independently associated with prostate cancer outcome. PATIENTS AND METHODS: From July 1994 to December 2002 309 consecutive men who had a radical retropubic prostatectomy for clinically localized disease had final GS 7 tumours in their prostatectomy specimen. Statistical analyses, including multivariate logistic regression, were used to evaluate the association between variables, i.e. standard preoperative features, stage, PSA progression, standard pathological variables, metastasis and death. RESULTS: In all, 215 patients (70%) had a final GS of 3 + 4 and 94 (30%) of 4 + 3. A final GS of 4 + 3 was associated with clinical stage T2 disease (P = 0.024), a higher biopsy GS (P < 0.001), seminal vesicle involvement (P < 0.001), positive surgical margins (P = 0.036), lymphovascular invasion (P = 0.018), metastases to regional lymph nodes (P = 0.008), higher preoperative serum prostate-specific antigen (PSA) (P = 0.042), and percentage positive biopsy cores (P = 0.006). In univariate analysis, patients with GS 4 +3 had a significantly higher risk of biochemical progression than those with GS 3 + 4 (P = 0.002). The 5-year actuarial risk of biochemical progression was 17% and 35% for GS 3 + 4 and 4 + 3, respectively (P = 0.0016). In a standard postoperative multivariate analysis, only preoperative PSA and metastases to regional lymph nodes were associated with PSA progression (P < 0.001 and 0.002, respectively). However, patients with final GS 4 + 3 had a shorter PSA doubling time after progression than those with GS 3 + 4 (P = 0.009). CONCLUSIONS: Tumours with a final GS of 4 + 3 are more aggressive than GS 3 + 4 tumours. Recognising the distinction in GS 7 between predominant 4 vs 3 scores after radical prostatectomy should improve the ability of clinicians to counsel patients. The GS 4 pattern deserves further molecular study.