Bone-targeted therapy in patients with renal cell carcinoma bone metastases undergoing palliative surgery.

Abstract

e16572 Background: RCC bone metastases (RCCBM) are found in 20-39% of patients and are becoming more prevalent. RCCBM cause significant morbidity and often require surgical intervention. Current bone-targeted therapies include bisphosphonates and denosumab. Previous literature has suggested that bisphosphonates do not improve survival or reduce skeletal related events and little has been published about the effect of denosumab. Here we present experience describing outcomes and therapeutic effect in patients with RCCBM following palliative surgery for bone metastasis. Methods: We performed a retrospective analysis of 226 patients with RCCBM who underwent orthopedic surgery at MD Anderson Cancer Center between 11/2005 – 8/2019. The Kaplan-Meier method and log-rank test were used to estimate and evaluate survival differences. Results: Patient characteristics included: median age 58.2, male 66.4%, clear cell histology 93.5%, metastatic at presentation 57.9%, nephrectomy 79.8% (63.9% prior to orthopedic intervention), received radiation to the surgical site (pre-op: 13.0%, post-op: 41.4%). First orthopedic intervention: resection arthroplasty 37.2%, curettage and intramedullary nailing (IMN) 18.6%, IMN 16.4%, open reduction internal fixation 15.0%, amputation 2.7%, 10.2% other. Pre-op therapy: bisphosphonate 12.4%, denosumab 5.8%, both 2.7%, none 79.2%. Post-op therapy: bisphosphonate 18.1%, denosumab 13.7%, both 0.9%, none 67.2%. With a median follow up of 3.1 years after first orthopedic intervention, median overall survival (OS) was 2.7 yr (95% CI 2.1 – 3.6). Progression free survival (PFS) was calculated from time of first surgery to either first progression or death; median PFS was 5.2 months (95% CI 4.6 – 7.5). Pre-op or post-op bone-targeted therapy was not significantly associated with PFS (yes vs no: Pre-op: median 3.4 vs 6.3 mth, p=0.42; Post-op: median 4.3 vs 5.8 mth, p=0.61) or OS (Pre-op: 2.1 vs 2.9 yr, p=0.45; Post-op: 2.4 vs 3.2 yr, p=0.18). Post-op denosumab compared to bisphosphonate was associated with increased PFS (9.6 vs 3.8 mth, p=0.03) and OS (3.3 vs 1.6 yr, p=0.02). However, post-op denosumab vs no bone-targeted therapy was not significantly associated with increased PFS (9.6 vs 5.8 mth, p=0.42) or OS (3.3 vs 3.2 yr, p=0.85). Of note, post-op bisphosphonate vs no bone-targeted therapy was associated with reduced PFS (3.8 vs 5.8 mth, p=0.04) and OS (1.6 vs 3.2 yr, p=0.01). Conclusion: Addition of bone-targeted therapy did not significantly improve PFS or OS in patients with RCCBM undergoing orthopedic intervention. Post-op denosumab was associated with better PFS and OS compared to bisphosphonates and bisphosphonates were associated with worse PFS and OS compared to no bone-targeted therapy. Patient selection for therapy may be an important source of bias. Prospective research is needed to clarify the role and selection of bone-targeted therapy in RCCBM patients.