# The Effects of Bone‐Remodeling Therapy on Survival, Pain, and Skeletal Related Events in the Setting of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From a Large Global Health Research Network (TriNetX)

## TL;DR

This study finds that bone-remodeling therapy with RANK ligand inhibitors improves survival and reduces pain-related issues in kidney cancer patients with bone metastases.

## Contribution

The study provides new evidence that RANK ligand inhibitors are more effective than bisphosphonates in improving survival and reducing skeletal-related events in RCC patients with bone metastases.

## Key findings

- Patients with RCC and bone metastases had a 2.5-fold higher 5-year mortality rate.
- RANK ligand inhibitors reduced opioid use and improved survival compared to bisphosphonates.
- RANK ligand inhibitors were associated with fewer skeletal-related events and hypocalcemia.

## Abstract

Renal cell carcinoma (RCC) is the most common renal malignancy—bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone‐remodeling therapy on mortality, incidence of skeletal‐related events, and opioid usage patterns in patients with BM.

A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

There were 139,859 patients diagnosed with RCC, of which 9021 had RCC with bone metastases (BM). Among these, 999 patients received only bisphosphonates (BPs), 973 received only RANK ligand inhibitors (RANKLi), and 119 patients initially received BPs before switching to RANKLi.

Presence of BM results in a ~2.5‐fold increase in 5‐year mortality rate (p < 0.0001) and a statistically significant increase in all SREs compared to those without BM. Patients receiving bisphosphonates had significantly higher rates of opioid use (p < 0.001) and comparable rates of chronic pain diagnoses to the overall BM group (p = 0.9217). In contrast, patients receiving RANKLi had a statistically significant reduction in opioid use (p < 0.001) and hypocalcemia (p < 0.001) compared to those on BPs, and an improved 5‐year survival rate (p < 0.0001) and median survival (p < 0.0001) relative to the overall BM cohort.

Patients receiving RANKLi have significantly improved survival, reduced opioid use and lower rates of SREs. Patients with RCC and BMs experienced significantly worse outcomes compared to those without BM. Surprisingly, among RCC patients with BMs, those treated with BPs only experienced even poorer outcomes.

In this retrospective population study containing 139,859 patients, subjects receiving RANK‐ligand inhibitors had improved survival and decreased rates of skeletal‐related events relative to the overall cohort of patients with metastatic bone lesions. Bone‐modifying agents may confer improved survival rates and decreased rates of skeletal‐related events.