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Relative increase of grade 4 and presence of invasive cribriform and/or intraductal carcinoma have individually been associated with adverse outcome of Gleason score 7 (GS 7) prostate cancer. The objective of this study was to investigate the relation of Gleason grade 4 tumor percentage (%GG4) and invasive cribriform and/or intraductal carcinoma in GS 3+4=7 prostate cancer biopsies. We reviewed 1031 prostate cancer biopsies from the European Randomized Study of Screening for Prostate Cancer. In total 370 men had G3+4=7. The relation of invasive cribriform and/or intraductal carcinoma and %GG4 with biochemical recurrence-free survival (BCRFS) after radical prostatectomy (n=146) and radiation therapy (n=195) was analyzed using Cox regression. Invasive cribriform and/or intraductal carcinoma occurred in 7/121 (6%) patients with 1-10% GG4, 29/131 (22%) with 10-25%, and 52/118 (44%) with 25-50% GG4 (P&lt;0.001). In crude analysis, both invasive cribriform and/or intraductal carcinoma (HR 2.72; 95% CI: 1.33-5.95; P=0.006) and 10-50% GG4 (HR 2.43; 95% CI: 1.10-5.37; P=0.03) were associated with BCRFS after prostatectomy. In adjusted analysis, invasive cribriform and/or intraductal carcinoma was an independent predictor for BCRFS (HR 2.40; 95% CI: 1.03-5.60; P=0.04) after prostatectomy, whereas percentage %GG4 (HR 1.00; 95% CI: 0.97-1.03; P=0.80) was not. While invasive cribriform and/or intraductal carcinoma (HR 2.58; 95% CI: 1.59-4.21; P&lt;0.001) performed better than 10-50% GG4 (HR 1.24; 95% CI: 0.67-2.29; P=0.49) for prediction of BCRFS after radiation therapy, both parameters were insignificant in analysis adjusted for prostate-specific antigen (P=0.001), positive biopsies (P&lt;0.001) and tumor volume (P=0.05). In conclusion, increased %GG4 is associated with invasive cribriform and/or intraductal carcinoma in GS 3+4=7 prostate cancer biopsies. Invasive cribriform and/or intraductal carcinoma is an independent parameter for BCR after prostatectomy, whereas %GG4 is not. The presence of invasive cribriform and/or intraductal carcinoma has to be included in pathology reports and should act as exclusion criterion for active surveillance.

modern pathology

Presence of invasive cribriform or intraductal growth at biopsy outperforms percentage grade 4 in predicting outcome of Gleason score 3+4=7 prostate cancer