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Cribriform/Intraductal Carcinoma Exhibits Superior Prognostic Value Over Gleason Pattern 4 percentage and Tertiary Pattern 5 in Gleason Pattern 4 Prostate Cancer
Alfred Anthony Barney, IV, MS1, Chaojiang Chen, MD2, Xiaoyang Liu, MD3, Shulin Wu, MD, PhD1, Sharron X. Lin, PhD1, Adam S. Feldman, MD, MPH1, Chin-Lee Wu, MD, PhD1, Douglas M. Dahl, MD1.
1Massachusetts General Hospital, Boston, MA, USA, 2The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, 3Peking University People's Hospital, Beijing, China.
BACKGROUND: In the absence of major pattern 5, Gleason pattern (GP) 4 encompasses Gleason scores 3+4, 4+3, and 4+4 at radical prostatectomy (RP). The associated adverse pathological features, including GP4 percentage (%GP4), cribriform/intraductal carcinoma (Crib/IDC), and tertiary pattern 5 (TP5), have become important factors for improving postoperative risk stratification. However, few studies have simultaneously evaluated the prognostic significance of %GP4, Crib/IDC, and TP5 specifically within GP4 disease.
METHODS: To investigate the prognostic significance of %GP4, Crib/IDC, and TP5 for biochemical recurrence (BCR) and metastasis in RP patients with GP4 disease. A retrospective cohort of RP patients with GP4 disease was identified from 2008-2014. Pathological variables included %GP4, Crib/IDC, and TP5. Patients were stratified by these features to assess their prognostic impact. Cox proportional hazards models were applied to evaluate their prognostic associations with BCR and metastasis.
RESULTS: Among 559 RP patients with Gleason pattern 4 disease, 55.1% had %GP4 ≥50%, 49.0% were Crib/IDC-positive, and 12.3% exhibited TP5, with these three variables exhibiting clear interrelationships. All three adverse morphological features were associated with significantly worse BCR-free and metastasis-free survival (log-rank P<0.001). In multivariable Cox regression, Crib/IDC demonstrated the strongest prognostic association, independently predicting an 80% increase in risk of BCR (HR 1.80, 95% CI 1.35-2.40) and a 90% increase in risk of metastasis (HR 1.90, 95% CI 1.19-3.03). %GP4 remained a significant continuous predictor of both endpoints (HR 1.009 per 1% increase for BCR; HR 1.016 for metastasis), whereas TP5 retained significance as a predictor only for BCR (HR 1.47, 95% CI 1.04-2.06) but not for metastasis (HR 1.31, P=0.298).
CONCLUSIONS: %GP4, Crib/IDC, and TP5 were interrelated and adverse features in RP patients with Gleason pattern 4 disease and were associated with worse BCR and metastasis outcomes. Crib/IDC demonstrated the strongest prognostic relevance, supporting standardized reporting beyond Gleason score alone.
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