These lesions have been found to be associated with adverse pathologic features including extraprostatic extension, seminal vesicle invasion, and positive surgical margins. Most importantly, multivariate analyses have shown CC and IDC to be linked with higher probabilities of biochemical recurrence (BCR), lymph node metastasis, distant metastasis, and cancer-specific death. Despite the growing evidence on the association of CC and IDC with adverse clinical outcomes, these lesions are not universally reported by pathologists, and current prostate cancer risk stratification tools do not take into consideration the presence of CC or IDC in prostate specimens.
Our previous studies demonstrated that adding CC and IDC presence in prostate biopsies strengthens the Cancer of Prostate Risk Assessment (CAPRA) and National Cancer Comprehensive Network (NCCN) pre-surgical prostate cancer risk stratification tools. The first study was based on a Toronto cohort, and the second study was a multi-institutional cohort (Toronto, Wisconsin, and Rotterdam). Both studies demonstrated improved BCR and event-free survival (EFS) predictions with the addition of the CC/IDC status.
In this study, we sought to determine the impact of CC and IDC on the CAPRA-S post-surgical risk stratification tool, which is commonly employed by clinicians to guide decisions around therapy after radical prostatectomy. The CAPRA-S score assigns points to the PSA level, Gleason score, positive surgical margin, seminal vesicle invasion, extraprostatic extension, and lymph node invasion. Patients are then classified into the low-risk (scores 0-2), intermediate-risk (scores 3-5), or high-risk (scores 6-12) group.
Our retrospective cohort included over eight hundred prostatectomies from three North American institutions: two from Toronto and one from Wisconsin. Kaplan Meier curves, stratified by CAPRA-S risk groups and by CAPRA-S plus CC/IDC status, were created to illustrate BCR-free survival and EFS (metastasis/death) probabilities. The model with the addition of CC/IDC status had a significantly better prognostic performance (higher Harrell’s concordance index) than the original model. Based on the Cox proportional hazards models, the addition of CC/IDC strengthened BCR stratification for the CAPRA-S intermediate-risk group (scores 3-5).
A subanalysis was conducted to assess the prognostic significance of CC and IDC separately (CC+/IDC+ vs CC+/IDC- vs CC-/IDC+ vs CC-/IDC-). This subcohort comprised over four hundred prostatectomies and included specimens where prostatic basal cell immunostains were used to classify cribriform lesions as CC (absence of basal cells) vs IDC (presence of basal cells). Kaplan Meier curves for BCR and EFS showed that patients with CC+/IDC+ had the worst BCR-free survival while patients with CC-/IDC- had the best BCR-free survival. Patients with CC+/IDC- had intermediate BCR-free probabilities that were not significantly different from those of patients with CC-/IDC+.
The first research group that studied the impact of CC/IDC in the CAPRA-S post-radical prostatectomy risk stratification tool, Jeyapala, and colleagues, found an improved BCR stratification in the CAPRA-S low-risk group when combined with the CC/IDC presence. Our study demonstrated the impact of CC/IDC in the CAPRA-S intermediate-risk group. We are convinced that a larger cohort with a longer follow-up time would have allowed us to show a more extensive impact of CC/IDC on BCR and EFS since our cohort lacked sufficient endpoints for analysis within risk groups. Nonetheless, our results reinforce the clinical significance of CC and IDC, and thus the importance of systematically reporting these lesions. Future contemporary prostate cancer risk stratification tools could benefit from integrating CC/IDC for better outcome predictions.
Written by: Ngoc-Nhu Jennifer Nguyen, MD1 & Michelle R. Downes, MD1,2
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
- Department of Anatomic Pathology, Precision Diagnostics & Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Yu Y, Lajkosz K, Finelli A, Fleshner N, van der Kwast TH, Downes MR. Impact of cribriform pattern 4 and intraductal prostatic carcinoma on National Comprehensive Cancer Network (NCCN) and Cancer of Prostate Risk Assessment (CAPRA) patient stratification. Mod Pathol. 2022;35(11):1695-1701.
- Downes MR, Liu KN, Yu Y, et al. Addition of Cribriform and Intraductal Carcinoma Presence to Prostate Biopsy Reporting Strengthens Pretreatment Risk Stratification Using CAPRA and NCCN Tools [published online ahead of print, 2023 Aug 1]. Clin Genitourin Cancer. 2023;S1558-7673(23)00182-9.
- Jeyapala R, Kamdar S, Olkhov-Mitsel E, et al. Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients. Clin Genitourin Cancer. 2022;20(3):e217-e226.