Total Neoadjuvant vs. Standard Perioperative Cisplatin/Doxorubicin Chemotherapy in Patients with Extremities Osteosarcoma: A Multi-Center Cohort Study

INTRODUCTION: Despite improvements in survival of patients with high-grade osteosarcoma after the implementation of perioperative chemotherapy, osteosarcoma remains among the most lethal cancers. Prescription of all chemotherapy courses before the surgery may provide this opportunity to eliminate micrometastases more efficiently, increase the chances of pathologic complete response and organ preserving surgery. This study aimed to compare the outcomes of total neoadjuvant chemotherapy vs. standard perioperative chemotherapy with cisplatin/doxorubicin regimen in patients with extremities osteosarcoma. METHODS: In this retrospective cohort, all patients with high-grade osteosarcoma admitted to oncologic centers affiliated to Iran University of Medical Sciences in Tehran, Iran from 2015 to 2021 were included. Organ preserving rates, pathologic responses, and survival of patients who received all six courses of cisplatin/doxorubicin regimen preoperatively were compared to those who received the regimen perioperatively. RESULTS: Sixty-three patients were enrolled (total neoadjuvant chemotherapy: 32 patients and perioperative chemotherapy: 31 patients). In total neoadjuvant chemotherapy and perioperative chemotherapy groups, favorable pathology responses (necrosis>90%) were reported in 80.6% and 15.6% of patients, respectively (p<0.001). With a median follow-up of 24 months, mean overall survival of total neoadjuvant chemotherapy and perioperative chemotherapy groups were 21.29 months (95% CI; 19.3-23.27) and 23.46 months (95% CI; 22.7-24.1), respectively (p=0.2). The mean disease-free survival of patients in total neoadjuvant chemotherapy and perioperative chemotherapy groups were 19.54 months (95% CI; 17.0-22.0) and 21.37 months (95% CI; 19.4-23.2), respectively (p=0.2). CONCLUSION: Our results showed that prescription of all courses of doxorubicin/cisplatin chemotherapy prior to surgery can increase favorable pathologic response rates, although this improvement is not translated into overall and disease-free survival benefits.