Cell Cycle Progression Score Identifies Biopsy-Undetected Grade Group 5 Prostate Cancer.

Area of Science:

• Oncology
• Urology
• Genomics

Background:

• Grade Group 5 (GG5) prostate cancer has the worst prognosis but is frequently missed during initial biopsy.
• Accurate identification of GG5 disease is crucial for appropriate patient management and treatment planning.
• Current risk stratification tools may not sufficiently identify patients with biopsy-undetected GG5 disease.

Purpose of the Study:

• To evaluate if the Cell Cycle Progression (CCP) score can identify biopsy-undetected GG5 prostate cancer.
• To determine if combining CCP score with the Cancer of the Prostate Risk Assessment (CAPRA) score improves risk stratification.
• To assess the predictive performance of CCP score and its combination with CAPRA compared to existing risk models.

Main Methods:

• 430 patients with biopsy-confirmed Grade Group 1-4 prostate cancer underwent Prolaris® testing (CCP score) before radical prostatectomy (RP).
• Logistic regression was used to assess the association between CCP score and pathological GG5 at RP.
• Predictive models (CCP, CAPRA, clinical cell-cycle risk [CCR] score) were compared using Area Under the Curve (AUC), Decision Curve Analysis (DCA), and Net Reclassification Improvement (NRI).

Main Results:

• CCP score independently predicted pathological GG5 disease (p < 0.001), even after adjusting for CAPRA score and biopsy core number.
• The combination of CCP and CAPRA scores (AUC=0.77) and the CCR score (AUC=0.74) demonstrated superior predictive performance compared to CAPRA alone (AUC=0.67).
• CCP score significantly improved risk classification, especially when combined with CAPRA, identifying a subset of patients with a substantially higher risk of GG5 disease (78% vs. 5.7%).

Conclusions:

• The CCP score adds significant value to initial prostate cancer risk assessment, particularly for patients categorized as low- to favorable-intermediate-risk by CAPRA.
• An elevated CCP score should prompt discussion regarding the increased risk of undetected GG5 disease and consideration of intensified management strategies.
• These findings are particularly relevant in non-surgical settings where definitive pathological information is unavailable, aiding in treatment decisions.