# Post-operative survival and use of systemic therapy in metastatic long-bone disease: 12 years of institutional experience

## TL;DR

The study shows that using targeted therapy alone before surgery improves survival for patients with long-bone metastases, while chemotherapy is linked to worse outcomes.

## Contribution

The study identifies how preoperative systemic therapy patterns influence survival in long-bone metastases, suggesting updated survival models are needed.

## Key findings

- Targeted therapy alone before surgery is associated with improved survival.
- Preoperative chemotherapy, alone or combined, correlates with worse survival.
- Use of preoperative targeted agents increased from 2% in 2015 to 43% in 2022.

## Abstract

•Preoperative systemic therapy patterns predict survival in long-bone metastases.•Targeted therapy alone before surgery is associated with improved survival.•Preoperative chemotherapy, alone or combined, correlates with worse survival.•Use of preoperative targeted agents for metastatic bone disease increased from 2% in 2015 to 43% in 2022.•Findings support updating survival models to include systemic treatment exposure.

Preoperative systemic therapy patterns predict survival in long-bone metastases.

Targeted therapy alone before surgery is associated with improved survival.

Preoperative chemotherapy, alone or combined, correlates with worse survival.

Use of preoperative targeted agents for metastatic bone disease increased from 2% in 2015 to 43% in 2022.

Findings support updating survival models to include systemic treatment exposure.

Survival prediction in metastatic long-bone disease is essential for surgical decision-making, yet the performance of legacy prognostic models has declined in the era of immunotherapy and molecularly targeted agents. As these systemic therapies become routine, treatment patterns themselves may influence survival in ways not captured by earlier models. We, therefore, quantified preoperative systemic therapy use over the last decade and evaluated its association with postoperative overall survival in patients undergoing surgery for long-bone metastases.

We conducted a retrospective cohort study of 975 consecutive adults who underwent surgery for long-bone metastases at two affiliated tertiary centers between January 2010 and June 2022. Preoperative systemic therapy was categorized into four groups: chemotherapy only, targeted therapy only, combined chemotherapy and targeted therapy, or neither. Postoperative was defined as time from surgery to death from any cause. We described temporal uptake of therapies by calendar year and assessed associations with postoperative survival using multivariable Cox regression adjusting for demographics, ECOG performance status, Katagiri primary tumor grouping, visceral/brain metastases, and laboratory variables. Adjusted survival over calendar time was summarized via marginal standardization at fixed horizons (1, 3, 12, and 24 months).

Use of targeted agents including checkpoint inhibitors rose markedly, from 2% in 2015 to 43% in 2022. In multivariable Cox models, preoperative chemotherapy alone was associated with worse survival versus no preoperative systemic therapy (HR 1.41, 95% CI 1.21–1.65; p < 0.01), as was combined chemotherapy plus targeted therapy (HR 1.24, 95% CI 1.05–1.47; p = 0.01). In contrast, targeted therapy alone before surgery was associated with better survival (HR 0.76, 95% CI 0.58–0.99; p = 0.04). Adjusted survival appeared to increase modestly across calendar years, but the pre-specified joint Wald test for the calendar year spline terms was not significant (p = 0.17), indicating a non-significant trend over time.

This study found that preoperative systemic therapy patterns are strongly associated with post-operative survival in metastatic long-bone disease: targeted therapy alone correlates with improved survival whereas preoperative use of chemotherapy—alone or combined with targeted agents—was associated with worse survival. These findings support incorporating contemporary treatment exposure into prognostic models and suggest that model recalibration to the immunotherapy era may be warranted.