Cell‐cycle risk score more accurately determines the risk for metastases and death in prostatectomy patients compared with clinical features alone

Abstract

Background: Prostate cancer treatment aims to prevent metastases and diseasespecific mortality. Pathologic parameters have limited ability to predict these outcomes, but biomarkers can improve risk discrimination. We evaluated the ability of cell-cycle progression and combined cell-cycle risk scores to predict metastases and disease-specific mortality after prostatectomy. Methods: Eligibility included (1) treatment with radical prostatectomy (1985-1997); (2) cell-cycle progression score; (3) preoperative prostatespecific antigen; (4) no neoadjuvant therapy; and (5) clinical follow-up (N = 360). Cancer of the prostate risk assessment postsurgical score was combined with cell cycle progression into the prespecified combined cell-cycle risk score. Hazard ratios (HRs) are reported per unit score. Results: In total, 11% (41/360) developed metastases and 9% (33/360) experienced disease-specific mortality. Combined cell-cycle risk score predicted metastases and disease-specific mortality post-radical prostatectomy (p < 1 × 10 −8). Adjusting for cancer of the prostate risk assessment postsurgical score, the combined cell-cycle risk score remained a predictor of metastases (HR = 3.03 [95% confidence interval (CI): 1.49, 6.20]; p = .003] and disease-specific mortality (HR = 3.40 [95% CI: 1.52, 7.59]; p = .004). Of patients with biochemical recurrence, 25% (41/163) developed metastases. Cancer of the prostate risk assessment postsurgical score was predictive of metastases postbiochemical recurrence but was improved by the addition of cell cycle progression (HR = 1.70 [95% CI: 1.14, 2.53]; p = .012). The combined cell-cycle risk was also prognostic of metastases post-biochemical recurrence (HR = 1.56 [95% CI: 1.20, 2.03]; p = .001). Conclusion: Combined cell-cycle risk and cell cycle progression scores predict metastases and disease-specific mortality post-radical prostatectomy and should help identify patients at greatest risk of treatment failure who might benefit from earlier intervention.

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy

“…CCR was significantly associated with MFS in the overall cohort, HR[2.0, and also in 163 men who had developed BCR, HR[1.6. 26 However, the cohort does not reflect contemporary diagnosis and treatment, and there was no information on whether any of the men with BCR had received SR. This is the first study to evaluate the association of CCP and PTEN with MFS in a contemporary cohort of men with exclusively I/HRPCa, and also in an I/HRPCa cohort exclusively receiving SR.…”

“…CCR was significantly associated with MFS in the overall cohort, HR=2.0, and also in 163 men who had developed BCR, HR=1.6. 26 However, the cohort does not reflect contemporary diagnosis and treatment, and there was no information on whether any of the men with BCR had received SR.…”

Can We Predict Prostate Cancer Metastasis Based on Biomarkers? Where Are We Now?

“…They used needle biopsies, and, in multivariate analyses, the CCP score's overall hazard ratio was 1.76 (95% CI (1.44, 2.14)) and the CCR's score was highly predictive, with a hazard ratio of 2.17 (95% CI (1.83, 2.57)). Swanson et al published [68] a study of 360 men in 2021 using sample tissue from radical prostatectomy specimens, in which CCR was demonstrated to be an independent predictor of metastatic disease and disease-specific mortality after RP (HR = 3.03 [95% confidence interval (CI): 1.49, 6.20]; p = 0.003) and disease-specific mortality (HR = 3.40 [95% CI: 1.52, 7.59]; p = 0.004), respectively. Tward et al addressed the potential benefits of using CCR to determine the need for adjuvant therapy in a study published in 2021 [69].…”