President Outcomes Insights, Inc. Calabasas, California, United States
Objective: There is no high level evidence in the medical literature that suggests that survival for osteosarcoma patients is improved with the current paradigm of neoadjuvant chemotherapy followed by surgery followed by adjuvant chemotherapy, rather than having surgery performed immediately after diagnosis followed by a complete course of chemotherapy. The objective of this study is to revisit the question of the relative timing of surgery and chemotherapy in the treatment of osteosarcoma of the extremities. The study aims to estimate the difference in overall survival for the standard of care (“Neoadjuvant First”) versus initiating surgery first followed by adjuvant chemotherapy (“Surgery First”).
Methods: Using the Surveillance, Epidemiology, and End Results (SEER) data, we identified patients diagnosed with a primary cancer of upper or lower extremity conventional or chondroblastic osteosarcoma between 2007 and 2019, who were age 5 to 29, and who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups. We also identified factors associated with survival and factors associated with the use of Surgery First
Results: Adjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In all sensitivity analyses of 5-year survival, the results were consistent, showing a 6.9% to 13.3% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age (per year; hazard ratio [HR] 1.04, 95% CI 1.01 to 1.07), larger tumor size (per centimeter; HR 1.03, 95% CI 1.00-1.05), the use of resection (vs. amputation; (HR 0.69, 95% CI 0.52-0.92), and stage 3-4 disease (vs. stage 1-2 disease; HR 3.09, 95% CI 2.36-4.04).
Conclusion: The evidence supporting neoadjuvant chemotherapy over up-front surgery for osteosarcoma is weak. This study, and its consistency with the results from the only previously published randomized trial on the effect of surgical timing relative to complete course of chemotherapy, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.
