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Active Monitoring, Surgery, and Radiotherapy for Cribriform-Positive and Cribriform-Negative Prostate Cancer: A
Nikita Sushentsev1,2, Anne Y Warren3, Richard Colling2
1Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
JAMA Oncology
|October 16, 2025
Summary
Cribriform prostate cancer significantly increases metastasis risk. Radiotherapy with neoadjuvant androgen deprivation therapy (ADT) reduced this risk, while surgery offered limited long-term benefit compared to active monitoring.
Area of Science:
- Oncology
- Urology
- Pathology
Background:
- Cribriform prostate cancer is linked to poor outcomes, but optimal treatment is uncertain due to limited data.
- The PROTECT trial provides a unique dataset for analyzing treatment strategies in localized prostate cancer.
Purpose of the Study:
- To investigate the association between cribriform-positive prostate cancer and 15-year metastasis risk.
- To compare the effectiveness of active monitoring, surgery, and radiotherapy with neoadjuvant androgen deprivation therapy (ADT) in patients with cribriform prostate cancer.
Main Methods:
- Secondary analysis of the PROTECT phase 3 randomized clinical trial.
- Centralized histopathologic review to identify cribriform-positive disease.
- Multivariable Cox proportional hazards regression to assess metastasis risk over 15 years.
Main Results:
- Cribriform-positive disease significantly increased metastasis risk (HR, 3.61).
- Radiotherapy with neoadjuvant ADT significantly reduced metastasis risk (HR, 0.35).
- Surgery delayed metastasis but did not significantly improve long-term outcomes versus active monitoring.
Conclusions:
- Cribriform morphology is an independent predictor of metastasis in prostate cancer.
- Radiotherapy with neoadjuvant ADT offers a significant survival benefit for patients with cribriform-positive disease.
- Patients with cribriform-negative disease have favorable outcomes, supporting active surveillance.
