What are the indications and survivorship of tumor endoprosthetic reconstructions for patients with extremity metastatic bone disease?

Given advances in therapies, endoprosthetic reconstruction (EPR) in metastatic bone disease (MBD) may be increasingly indicated. The objectives were to review the indications, and implant and patient survivorship in patients undergoing EPR for MBD.

). 5,6 EPR has many distinct advantages over fixation, such as facilitating a single definitive surgery, early mobilization and weight bearing, and potentially minimizing repeat trips to the operating room due to implant failure. 5,7,8 Before the transition from custom to modular tumor endoprosthetics with more reliable modern designs, 9 EPR use was limited in MBD patients due to lack of off the shelf availability and length of fabrication.
Patient survival estimates are important when considering implant choice. Advances in cancer therapies such as targeted treatments and immunotherapies have resulted in improved patient survival for certain cancer types such as advanced renal cell carcinoma and non-small cell lung cancer. 10,11 While survival in patients with MBD requiring orthopedic surgery has shown unclear temporal trends, 12 a recent study of femoral metastasis secondary to renal and lung carcinoma demonstrated measurable impact of biologic anti-neoplastic agents on patient survival. 13 In general, the orthopedic oncology community has placed greater consideration on the benefits of en bloc resection and EPR for appendicular MBD in the appropriate clinical scenario. [13][14][15][16] Using a large retrospective dataset, we asked (1)

| Surgical interventions
Patients were included in this study if they underwent EPR for an MBD indication. Indications for EPR were coded for all patients, and were categorized into actualized pathologic fractures, impending pathologic fractures, and EPR for failed previous surgical fixation. Those

| Other data sources
Use of immunotherapy and targeted therapies was factored into analysis for patients with sensitive primary cancers (renal cell, lung, and melanoma). Immunotherapy was approved for use in 2015 by the FDA and Health Canada, and therefore cases treated after the year 2015 were included for assessment of frequency of immunotherapy use in patients who were undergoing EPR for failed previous surgical fixation. 18 PathFx v3.0 (https://www.pathfx.org) was utilized as a retrospective audit of predicted patient survival in patients who failed previous surgical fixation. 19,20

| Statistical analysis
Descriptive statistics were used to summarize demographic and surgical variables. Categorical variables were analyzed using a chi-square (χ 2 ) test. Implant survival and overall patient survival and was calculated using the Kaplan-Meier survival analysis and associated 95% confidence intervals (CIs). Statistics were conducted using GraphPad Prism 9 and Stata (Release 16; StataCorp LLC).

| Patient demographics
A total of 115 patients were included with a mean age of 60.6 (SD 14.7) and 59 (51.3%) were female (

| EPRs for failed previous surgical fixation
Patient estimated survival was retrospectively predicted at the time of initial surgical fixation with data available for 12 patients (Figure 4;

| DISCUSSION
The musculoskeletal oncology community identified delineating the role of en bloc resection and reconstruction versus stabilization in MBD as a top research priority in orthopedic oncology. 21 Tumor EPRs for MBD may be an increasingly valuable tool over conventional fixation methods in the oncology surgeon's clinical decision-making process as patient survival for various cancer subtypes improves. 13 In this study a multicenter database review of patients undergoing en bloc resection and tumor EPR for extremity MBD was performed.
The most common primary histologies in this series were renal cell carcinoma, breast cancer and lung cancer, which is consistent with previous series' assessing EPR in MBD. 5,6 In comparison to a historic cohort at UCLA , EPRs were more commonly performed in patients with lung cancer (13.9% in this study vs. 5.4% in historic cohort). 7 Actualized pathologic fracture was the most common surgical indication for EPR (consistent with published data on proximal femur EPR for MBD), 22 followed closely by impending fracture and failed surgical fixation. PFRs and PHRs were the two most common endoprosthetics employed in this dataset, and implant longevity was favorable and greatly exceeded patient survival. Ten  There are limitations to this study in addition to the inherent biases of being a retrospective data capture. As both centers included are tertiary musculoskeletal oncology centers, there is a possibility of referral bias. Cases included spanned multiple decades from 1992 to 2022, which is both a strength of the study as well as a limitation due to more recent advances in therapies and advances in implant design and evolving surgical indications. We did not include a matched cohort of patients who underwent surgical fixation which did not allow for a matched comparison; however, this was not suited to the scope of our clinical questions.

| CONCLUSIONS
The role of en bloc resection and EPR in patients with MBD is a top priority in orthopedic oncology. These data provide an updated analysis of the indications, outcomes, and complications in patients with MBD undergoing EPR. When compared to fixation techniques and when done for the appropriate indication, EPR provides a reliable and durable surgical reconstruction that will likely last beyond the duration of the patient's life. Those undergoing EPR for failed surgical fixation were more likely to have a diagnosis of renal cell or lung cancer.