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Background <p>In the absence of primary or secondary pattern 5, Gleason pattern 4 encompasses Gleason scores 3 + 4, 4 + 3, and 4 + 4 at radical prostatectomy (RP). The associated adverse pathological features, including Gleason pattern 4% (%GP4), cribriform/intraductal carcinoma (Crib/IDC), and tertiary pattern 5 (TP5), have become particularly important factors for improving postoperative risk stratification. However, few studies have simultaneously evaluated the prognostic significance of %GP4, Crib/IDC, and TP5 specifically within Gleason pattern 4 disease.</p> Objective <p>To investigate the prognostic significance of %GP4, Crib/IDC and TP5 for biochemical recurrence (BCR) and metastasis in RP patients with Gleason pattern 4 disease.</p> Methods <p>A retrospective cohort of RP patients with Gleason pattern 4 disease was identified from 2008 to 2014 at Massachusetts General Hospital. 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.</p> Results <p>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 survival and metastasis-free survival (log-rank <i>P</i> &lt; 0.001). In multivariable Cox regression, Crib/IDC demonstrated the strongest prognostic association, independently predicting an 80% increased risk of BCR (HR 1.80, 95% CI 1.35–2.40) and 90% increased 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, <i>P</i> = 0.298).</p> Conclusion <p>%GP4, Crib/IDC, and TP5 were correlated and adverse features in RP patients with Gleason pattern 4 disease and were associated with worse oncologic outcomes. Crib/IDC demonstrated the strongest prognostic relevance, supporting consideration of standardized reporting beyond Gleason score alone.</p>

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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

  • 期刊论文

  • 发表日期：

    2026年5月12日

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  • Chaojiang Chen,
  • Xiaoyang Liu,
  • Shulin Wu,
  • Sharron X. Lin,
  • Adam S. Feldman,
  • Chin-Lee Wu,
  • Douglas M. Dahl

摘要

Background

In the absence of primary or secondary pattern 5, Gleason pattern 4 encompasses Gleason scores 3 + 4, 4 + 3, and 4 + 4 at radical prostatectomy (RP). The associated adverse pathological features, including Gleason pattern 4% (%GP4), cribriform/intraductal carcinoma (Crib/IDC), and tertiary pattern 5 (TP5), have become particularly important factors for improving postoperative risk stratification. However, few studies have simultaneously evaluated the prognostic significance of %GP4, Crib/IDC, and TP5 specifically within Gleason pattern 4 disease.

Objective

To investigate the prognostic significance of %GP4, Crib/IDC and TP5 for biochemical recurrence (BCR) and metastasis in RP patients with Gleason pattern 4 disease.

Methods

A retrospective cohort of RP patients with Gleason pattern 4 disease was identified from 2008 to 2014 at Massachusetts General Hospital. 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 survival and metastasis-free survival (log-rank P < 0.001). In multivariable Cox regression, Crib/IDC demonstrated the strongest prognostic association, independently predicting an 80% increased risk of BCR (HR 1.80, 95% CI 1.35–2.40) and 90% increased 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).

Conclusion

%GP4, Crib/IDC, and TP5 were correlated and adverse features in RP patients with Gleason pattern 4 disease and were associated with worse oncologic outcomes. Crib/IDC demonstrated the strongest prognostic relevance, supporting consideration of standardized reporting beyond Gleason score alone.