Should the Use of Biologic Agents in Patients With Renal and Lung Cancer Affect Our Surgical Management of Femoral Metastases?
Authors: Gutowski Christina J. , Zmistowski Benjamin , Fabbri Nicola , Boland Patrick J. , Healey John H. 
Published: September 2018

Abstract

Background
Biologic agents may prolong survival of patients with certain kidney and lung adenocarcinomas that have metastasized to bone, and patient response to these agents should be considered when choosing between an endoprosthesis and internal fixation for surgical treatment of femoral metastases.

Questions/purposes
Among patients undergoing surgery for femoral metastases of lung or renal cell carcinoma, (1) Does survival differ between patients who receive only cytotoxic chemotherapy and those who either respond or do not respond to biologic therapy? (2) Does postsurgical incidence of local disease progression differ between groups stratified by systemic treatment and response? (3) Does implant survival differ among groups stratified by systemic treatment and response?

Methods
From our institutional longitudinally maintained orthopaedic database, patients were identified by a query initially identifying all patients who carried a diagnosis of renal cell carcinoma or lung carcinoma. Patients who underwent internal fixation or prosthetic reconstruction between 2000 and 2016 for pathologic fracture of the femur and who survived ≥ 1 year after surgery were studied. Patients who received either traditional cytotoxic chemotherapy or a biologic agent were included. Patients were classified as responders or nonresponders to biologic agents based on whether they had clinical and imaging evidence of a response recorded on two consecutive office visits over ≥ 6 months. Endpoints were overall survival from the time of diagnosis, survival after the femoral operation, evidence of disease progression in the femoral operative site, and symptomatic local disease progression for which revision surgery was necessary. Our analysis included 148 patients with renal (n = 26) and lung (n = 122) adenocarcinoma. Fifty-one patients received traditional chemotherapy only. Of 97 patients who received a biologic agent, 41 achieved a response (stabilization/regression of visceral metastases), whereas 56 developed disease progression. We analyzed overall patient survival with the Kaplan-Meier method and used the log-rank test to identify significant differences (p < 0.05) between groups.

Results
One-year survival after surgery among patients responsive to biologic therapy was 61% compared with 20% among patients nonresponsive to biologics (p < 0.001) and 10% among those who received chemotherapy only (p < 0.009). With the number of patients we had to study, we could not detect any difference in local progression of femoral disease associated with systemic treatment and response. Radiologic evidence of periimplant local disease progression developed in three (7%) of 41 patients who responded to biologic treatment, two (3%) of 56 patients nonresponsive to biologics, and one (2%) of 51 patients treated with traditional chemotherapy. With the numbers of patients we had, we could not detect a difference in patients who underwent revision. All three patients responsive to biologics who developed local recurrence underwent revision, whereas the two without a response to biologics did not.

Conclusions
Biologic therapy improves the overall longevity of some patients with lung and renal metastases to the femur in whom a visceral disease response occurred. In our limited cohort, we could not demonstrate an implant survival difference between such patients and those with shorter survival who may have had more aggressive disease. However, an increased life expectancy beyond 1 year among patients responsive to biologics may increase risk of mechanical failure of fixation constructs.

Level of Evidence
Level III, therapeutic study.