The clinical cell-cycle risk (CCR) score is associated with metastasis after radiation therapy and provides guidance on when to forgo combined androgen deprivation therapy with dose-escalated radiation

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.

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.

Background Validation of biomarker‐based prognostic models to improve risk stratification in men with localized prostate cancer (PrCa) remains a clinical need. It has previously been shown that the cell cycle progression (CCP) test provides significant, independent prognostic information for men who were incidentally diagnosed with PrCa after transurethral resection of the prostate (TURP) and were conservatively managed. Aim The results have been extended in a newly analyzed retrospective cohort of UK men diagnosed through TURP biopsy (TURP1B; N = 305). Methods and Results The CCP score was derived from TURP biopsy tissue and combined with a modified UCSF Cancer of the Prostate Risk Assessment score (CAPRA) to generate the clinical cell‐cycle risk score (CCR). The primary endpoint was PrCa‐specific mortality (PSM). Hazard ratios (HR) were calculated for a one‐unit change in score. Median follow‐up was 9.6 (IQR: 5.4, 14.1) years, and 67 (22%) men died from PrCa within 10 years of diagnosis. The median CCP score was 1.1 (IQR: 0.6, 1.7). In univariate analyses, CCR proved a significant prognosticator of PSM (HR per unit score change = 2.28; 95% CI: 1.89, 2.74; P = 1.0 × 10 −19 ). In multivariate analyses, CCR remained a significant prognosticator of PSM after adjusting for CAPRA (HR per unit score change = 4.36; 95% CI: 2.65, 7.16; P = 1.3 × 10 −8 ), indicating that its molecular component, CCP, provides significant, independent prognostic information. Conclusion These findings validate a combined clinicopathologic and molecular prognostic model for conservatively managed men who are diagnosed through TURP, supporting the use of CCR to inform clinical management.

278 Background: Professional guidelines recommend hereditary cancer risk assessment (HCRA) for men with prostate cancer to inform both risk of cancer (primary or subsequent) and treatment decisions. The objectives of the study were to evaluate the feasibility of integrating a HCRA protocol in urology practice for patients with prostate cancer and determine the response of providers and patients to the HCRA protocol. Methods: This prospective study was divided into 4 segments: process integration (4 wks.), practice (4 wks.), post-integration (8 wks.), and follow up (10 wks.). Study site staff were trained to perform HCRA for men with prostate cancer (integration). The sites then incorporated recommendations from the integration process into their normal practice workflow (practice). During the post-integration period, the HCRA process was implemented with eligible patients consented to participate. Eligible patients were ≥18 years old, had a personal history of prostate cancer, and met National Comprehensive Cancer Network guidelines for genetic testing (2.2018). Patients and providers completed surveys regarding testing ≥ 8 weeks of test delivery or 1 week of end of data collection period, respectively (follow up). Results: In the 8 weeks prior to the study, 4.2% of patients completed testing at the study sites. During the study, 8.4% of patients completed testing, about 1/2 of eligible patients screened. Of all patients who completed testing and consented for their results to be summarized (N = 182), 10.4% (N = 19) tested positive for a single pathogenic variant (PV; monoallelic MUTYH N = 4; BRCA2 N = 3; ATM, BRCA1, BRIP1, CHEK2, HOXB13 N = 2 each; RAD51C, RAD51D N = 1 each). Not all men who tested positive or a PV reported a family history of cancer and not all PVs detected were in known prostate cancer risk genes. During follow up, most providers (61.0%) felt HCRA was as important as other assessments regularly performed and 68.3% planned to continue to use the HCRA process. In contrast, only 9.8% of providers did not believe HCRA was as important and 12.2% did not plan to continue to use the process. Of the patients that responded to the survey (N = 166), most had shared (62.0%) or planned to share (25.3%) their results with family members post-testing. Conclusions: Urologists and patients responded favorably to HCRA protocol integration. Based on this study, education around and incorporation of an HCRA process in a community urology practice setting for men with prostate cancer appears effective at increasing appropriate uptake of genetic testing. Clinical trial information: NCT04015102.