Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Grade Group 5 (GG5) prostate cancer carries the poorest prognosis, yet it is often undetected at biopsy. We evaluate whether Cell Cycle Progression (CCP) score identifies biopsy-undetected GG5 disease and improves risk stratification when combined with Cancer of the Prostate Risk Assessment (CAPRA) score. METHODS: A total of 430 patients with biopsy-confirmed GG1-4 underwent Prolaris® testing before immediate radical prostatectomy (RP). Logistic regression assessed the association between CCP score and pathological GG5 at RP. Predictive models using CCP, CAPRA, and clinical cell-cycle risk (CCR) score were compared using area under the curve (AUC), decision curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: Although GG5 was not frequent (7.2%), CCP score independently predicted GG5 (p < 0.001) before and after adjusting for CAPRA and biopsy core number obtained. AUCs were 0.71 (95% CI: 0.60-0.83) for CCP, 0.67 (0.56-0.77) for CAPRA, 0.77 (0.67-0.87) for CCP + CAPRA, and 0.74 (0.64-0.84) for CCR. Both CCP + CAPRA and CCR outperformed CAPRA (DeLong's test, p = 0.008 and 0.001, respectively). DCA showed greater net benefit for CCP + CAPRA at thresholds 0.05-0.50 and for CCR at 0.05-0.40. CCR score yielded a higher overall NRI of 0.90 (95% CI: 0.55-1.20), improving classification for both events and non-events. A significant positive CCP-CAPRA interaction was identified: GG5 was observed in 5.7% (24/421) of patients with CCP ≤ 4.6 and/or CAPRA ≤ 4, versus 78% (7/9) with both > 4.6 and ≥ 5 (p = 0.039). CONCLUSIONS: Our data suggests that CCP score adds value to initial risk assessment, particularly in CAPRA-defined low- to favorable-intermediate-risk patients. An elevated CCP score should prompt counseling on the increased risk of biopsy-undetected GG5 disease and consideration of intensified management, such as RP or radiotherapy with prolonged androgen deprivation therapy within a multimodal framework. This is especially relevant in non-surgical settings where final pathology is unavailable. CLINICAL TRIAL REGISTRATION: N/A.
Source: The Prostate
DOI: 10.1002/pros.70112
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417422500