Predictors of skeletal‐related events and mortality in men with metastatic, castration‐resistant prostate cancer: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

Abstract

Background Although skeletal‐related events (SREs) are linked with a reduced quality of life and worse outcomes, to the authors' knowledge the factors that predict SREs are minimally understood. The objective of the current study was to identify predictors of SREs and all‐cause mortality among men with metastatic castration‐resistant prostate cancer (mCRPC). Methods Data were collected on 837 men with bone mCRPC at 8 Veterans Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 2000 through 2017. Patients were followed to assess development of SREs (pathological fracture, radiotherapy to bone, spinal cord compression, or surgery to bone). Cox proportional hazards models were used to evaluate predictors of SREs and mortality. Results Of the 837 men with bone mCRPC, 287 developed a SRE and 740 men died (median follow‐up, 26 months). Bone pain was found to be the strongest predictor of SREs (hazard ratio [HR], 2.96; 95% CI, 2.25‐3.89). A shorter time from CRPC to the development of metastasis (HR, 0.92; 95% CI, 0.85‐0.99), shorter progression to CRPC (HR, 0.94; 95% CI, 0.91‐0.98), and visceral metastasis at the time of diagnosis of bone metastasis (HR, 1.91; 95% CI, 1.18‐3.09) were associated with an increased risk of SREs. Ten or more bone metastases (HR, 2.17; 95% CI, 1.72‐2.74), undergoing radical prostatectomy (HR, 0.73; 95% CI, 0.61‐0.89), shorter progression to CRPC (HR, 0.97; 95% CI, 0.94‐0.99), older age (HR, 1.03; 95% CI, 1.02‐1.04), higher prostate‐specific antigen level at the time of diagnosis of metastasis (HR, 1.21; 95% CI, 1.14‐1.28), bone pain (HR, 1.44; 95% CI, 1.23‐1.70), and visceral metastasis (HR, 1.72; 95% CI, 1.23‐2.39) were associated with an increased mortality risk. Conclusions Among men with bone mCRPC, bone pain was found to be the strongest predictor of SREs and the number of bone metastases was a strong predictor of mortality. If validated, these factors potentially may be used for risk stratification and for SRE prevention strategies.

Symptomatic Skeletal Events and the Use of Bone Health Agents in a Real-World Treated Metastatic Castration Resistant Prostate Cancer Population: Results From the CAPRI-Study in the Netherlands

“…We also investigated which patients can benefit from BHAs based on their risk of SSEs. Although other studies report elevated ALP, visceral metastases, Gleason score ≥7 and short interval between the initiation of ADT and CRPC diagnosis as risk factors, we have found that only patients with a prior SSE and with pain and/or opioid use were at higher risk of developing an SSE [33][34][35]. Patients who had either a prior SSE or pain and/or opioid use (or both) benefited the most from early BHA use.…”

“…In our cohort, median SSE-free survival was 12.9 months. The difference in SSE-FS in our observation can be explained by a high prevalence of SSEs compared to other studies [16,17,33,35,40]. We only included real-world patients who tend to have worse prognostic features than trial populations and thus are likely to have shorter SSE-FS.…”

Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine

“…Multiplex analysis of whole genome somatic genomic defects and outcome is needed in mPC cohorts to evaluate relative utility of specific genomic biomarkers. Pain Bone pain associated with worse OS in patients with mCRPC [70] ; more pain associated with worse OS in patients with mCRPC [71] ; achieving a pain response to treatment associated with better OS [57] ; in current study, Gleason grade pattern and time to first severe pain linked, needs to be validated Bone pain is associated with increased risk of skeletal-related events [70] . Testing pain as a specific outcome variable is indicated.…”

Homologous Recombination Repair Gene Variants and Outcomes Among Patients With Prostate Cancer Treated With Poly (ADP-ribose) Polymerase Inhibitors

“…In the United States, prostate cancer is the second most common malignancy among men, with an annual incidence of approximately 250,000. 1 Although most patients with early-stage prostate cancer share a favorable prognosis, patients with metastatic castrate-resistant prostate cancer (mCRPC) frequently have poor outcomes, with a median overall survival ranging from 13 months 2 to 32 months. 3,4 Unfortunately, despite an overall decline in the incidence of prostate cancer in the United States, the incidence of metastatic prostate cancer continues to rise.…”

“…Department of Medicine, Duke University Health System, Durham, NC2 Division of Hematology-Oncology, Durham Veterans Affairs Medical Center, Durham, NC3 Raymond G. Murphy New Mexico Veterans Affairs Medical Center, Section of Hematology/Oncology, Albuquerque, NM4 National Oncology Program Office, Department of Veterans Affairs, Durham, NC5 Veterans Affairs Boston Healthcare System, Jamaica Plain Campus, Boston, MA6 Duke University Health System, Divisions of Medical Oncology, Hematology and Cell Therapeutics, Durham, NC7 Veterans Affairs Puget Sound Health Care System, Division of Hematology-Oncology, Seattle, WA…”