Personalizing Localized Prostate Cancer: Validation of a Combined Clinical Cell-cycle Risk (CCR) Score Threshold for Prognosticating Benefit From Multimodality Therapy

Abstract

Using a retrospective, multi-institutional cohort of men with prostate cancer (N [ 718), this study evaluated a score that combines a genome expression classifier and clinical information to prognosticate progression to metastatic disease in various treatment contexts. A score threshold identified men with intermediate-and high-risk prostate cancer who could safely forgo multimodal therapy. Introduction: The combined clinical cell-cycle risk (CCR) score is a validated model that combines the cell-cycle progression (CCP) score with the University of California San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score. This score determines the risk of progressive disease for men with prostate cancer. Here, we further validate the prognostic ability of the CCR score and evaluate its ability to help determine which patients may safely forgo multimodality therapy. Patients and Methods: We evaluated the CCR and a CCR-based multimodality threshold (2.112) in a retrospective, multi-institutional cohort of men with National Comprehensive Cancer Network intermediate-or high-risk localized disease (N ¼ 718). These men received single or multimodality therapy (androgen deprivation with radiation [RT], or surgery with adjuvant RT or hormones). Results: CCR score prognosticated metastasis for single-modality therapy, as a continuous variable (hazard ratio, 3.97; 95% confidence interval [CI], 2.61-6.06) and when dichotomized at the threshold (hazard ratio, 15.90; 95% CI, 5.43-46.52). The 10year Kaplan-Meier risk for those receiving single-modality (RT or surgical) therapy with CCR scores below and above the threshold for single-modality treatment was 4.3% (95% CI, 1.0%-17.1%) and 20.4% (95% CI, 13.2%-30.7%), respectively. Using the threshold, 27% of men with newly diagnosed high-risk and 73% with unfavorable intermediate-risk disease could avoid multimodality therapy. Conclusions: Patients with CCR scores below the multimodality threshold (2.112) may safely forgo multimodality therapy. The CCR score can be used as a decision aid to counsel men whether or not single-modality therapy would be sufficient for their intermediate-or high-risk prostate cancer.

Using the Cell-Cycle Risk Score to Predict the Benefit of Androgen-Deprivation Therapy Added to Radiation Therapy in Patients With Newly Diagnosed Prostate Cancer

“…To address this critical need, we quantified how adding ADT to RT reduces the risk of metastasis in individual patients by applying the metaanalysis results 32 to personalized risk estimates derived from the CCR score, which combines molecular and clinical prognostic information. [22][23][24][25][26]29,30,[33][34][35] The results of the current study revealed that the CCR score can inform personalized ARR because of treatment with ADT, with a substantially reduced 10-year risk of metastasis predicted in those above the Prolaris MMT threshold. This methodology can be applied to any validated nomogram or biomarker that produces an individual risk estimate for metastasis.…”

“…The RT-alone cohort included 467 patients from two previously described and published, retrospective cohorts who were treated with RT alone as a single modality. 25,26 The clinical cohort included 56,485 patients who underwent a clinical Prolaris biopsy test between January 1, 2020, and October 31, 2022. These patients were untreated at the time of biopsy used for testing, and their clinical follow-up, including treatment choices, is unknown.…”

“…[22][23][24] Retrospective analyses have also shown the usefulness of CCR in identifying patients who may benefit more from multimodal therapy with RT 1 ADT. 25,26 Knowledge of personalized ARR and NNT for RT 1 ADT can help patients understand risks and benefits of using combined modality therapy over RT alone and aid in making treatment intensification decisions. This study describes the derivation of personalized ARR and NNT when adding ADT to RT in individuals with localized prostate cancer.…”

Concordance of MRI-Guided Fusion and Systematic 12-Core Prostate Biopsy for the Detection of Prostate Cancer

“…Novel commercially available clinical-genomic tests four kallikrein panel algorithm (4Kpanel), Oncotype DX, Prolaris, and Decipher can also aid decision making for clinicians. For example, these tests have been shown to reclassify men with NCCN low-risk PCa at greater risk for development of metastatic disease (24,25), identify men with NCCN high-risk PCa who may be candidates for active surveillance (26), and increase confidence for community providers to recommend active surveillance (27). In the future it is possible these tests may help personalize biopsy decisions for many patients.…”

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

“…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]. They used the CCR score and defined a multimodality therapy threshold for patients who had radiotherapy or surgery to assess the need for ADT or radiation, respectively.…”