Clinical Outcome Following Prolonged Neoadjuvant Chemotherapy and Delayed Surgery in Osteosarcoma Patients: An Evidence-based Clinical Review

Waluyo Sugito, Achmad Fauzi Kamal


Background: The incidence of osteosarcoma reached 16.8 cases annually at dr. Cipto Mangunkusumo Hospital in 1995-2008. Previous studies suggested that prolonged neoadjuvant chemotherapy followed by delayed surgery improves the clinical outcome. Prolonged neoadjuvant chemotherapy followed by delayed surgery commonly occurs in Indonesia, as diagnostic imaging and surgery waiting list will delay the surgery. The aim of this study is to observe the survival rate and the event-free survival rate of osteosarcoma patients with prolonged neoadjuvant chemotherapy and delayed surgery. Methods: This review included randomized controlled trials (RCTs), cohort studies, retrospective cohort studies, clinical trials, and reviews. Literature search was conducted through MEDLINE (PubMed search engine), Cochrane Central Register of Controlled Trial, and Scopus. The studies were screened and selected according to inclusion criteria by author and contributors independently. Results: Six studies were included in the qualitative synthesis of this study. Overall survival rate, event-free survival rate, histological response and recurrence as well as neoadjuvant chemotherapy duration, cycle and regiment were assessed in this study. Conclusion: Prolonged neoadjuvant chemotherapy and delayed surgery results in 5-years survival rate of 43.2% to 96.6% and 5-years event-free survival rate of 35.7% to 86.4%.


Osteosarcoma; neoadjuvant chemotherapy; delayed surgery; osteosarcoma


de Azevedo J, Fernandes T, Fernandes J, et al. Biology and pathogenesis of human osteosarcoma (Review). Oncol Lett [Internet]. 2019 Dec 18 [cited 2020 Jan 26]; Available from:

Geller DS, Gorlick R. Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol. 2010;8(10):705–18.

Durfee RA, Mohammed M, Luu HH. Review of osteosarcoma and current management. Rheumatol Ther. 2016;3(2):221–43.

Ritter J, Bielack SS. Osteosarcoma. Ann Oncol. 2010;21 Suppl 7:vii320-325.

Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages, and elderly persons. Int J Cancer. 2009;125(1):229–34.

Ottaviani G, Jaffe N. The Epidemiology of Osteosarcoma. Cancer Treat Res. 2010;152:3–13.

Kamal AF, Widyawarman H, Husodo K, Hutagalung EU, Rajabto W. Clinical outcome and survival of osteosarcoma patients in Cipto Mangunkusumo Hospital: Limb salvage surgery versus amputation. Acta Med Indones. 2017;48(3):175-83.

Abou Ali B, Salman M, Ghanem KM, et al. Clinical prognostic factors and outcome in pediatric osteosarcoma: Effect of delay in local control and degree of necrosis in a multidisciplinary setting in Lebanon. JGO. 2019;(5):1–8.

Vasquez L, Silva J, Chavez S, et al. Prognostic impact of diagnostic and treatment delays in children with osteosarcoma. Pediatric Blood & Cancer. 2020;67(4):e28180.

Moore D, Luu H. Osteosarcoma. Cancer Treat Res. 2014;162:65–92.

Zhang Y, Yang J, Zhao N, et al. Progress in the chemotherapeutic treatment of osteosarcoma (Review). Oncology Letters. 2018;16(5):6228–37.

Zhu W, Zhu L, Bao Y, Zhong X, Chen Y, Wu Q. Clinical evaluation of neoadjuvant chemotherapy for osteosarcoma. J BUON. 2019;24:1181–5.

Xu M, Xu S, Yu X. Marginal resection for osteosarcoma with effective neoadjuvant chemotherapy: long-term outcomes. World J Surg Onc. 2014;12(1):341.

Xu J, Xie L, Guo W. Neoadjuvant chemotherapy followed by delayed surgery: Is it necessary for all patients with nonmetastatic high-grade pelvic osteosarcoma? Clinical Orthopaedics and Related Research. 2018;476(11):2177–86.

Ferrari S, Bertoni F, Mercuri M, et al. Predictive factors of disease-free survival for non-metastatic osteosarcoma of the extremity: An analysis of 300 patients treated at the Rizzoli Institute. Ann Oncol. 2001;12(8):1145–50.

Rosen G, Marcove RC, Caparros B, Nirenberg A, Kosloff C, Huvos AG. Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery. Cancer. 1979;43(6):2163–77.

Wilkins RM, Cullen JW, Camozzi AB, Jamroz BA, Odom L. Improved survival in primary nonmetastatic pediatric osteosarcoma of the extremity. Clinical Orthopaedics and Related Research. 2005;438:128–36.

Bacci G, Picci P, Ferrari S, et al. Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin. Cancer. 1993;72(11):3227–38.

Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis. 2010;5:17.

Fagioli F, Biasin E, Mereuta OM, et al. Poor prognosis osteosarcoma: new therapeutic approach. Bone Marrow Transplant. 2008;41(S2):S131–4.

Ngan RKC. Chemotherapy for non-metastatic high-grade osteosarcoma of extremity - Is neoadjuvant better than adjuvant? J Hong Kong Coll Radiol. 2003;6:7–14.

Friebele JC, Peck J, Pan X, Abdel-Rasoul M, Mayerson JL. Osteosarcoma: A meta-analysis and review of the literature. Am J Orthop (Belle Mead NJ). 2015;44(12):547–53.

Kleinerman E. Maximum benefit of chemotherapy for osteosarcoma achieved—what are the next steps? Lancet Oncol. 2016;17(10):1340–2.

Bishop MW, Chang Y-C, Krailo MD, et al. Assessing the prognostic significance of histologic response in osteosarcoma: A comparison of outcomes on CCG-782 and INT0133—A Report From the Children’s Oncology Group Bone Tumor Committee. Pediatr Blood Cancer. 2016;63(10):1737–43.

Miwa S, Takeuchi A, Ikeda H, et al. Prognostic value of histological response to chemotherapy in osteosarcoma patients receiving tumor-bearing frozen autograft. PLOS ONE. 2013;8(8):e71362.

Faisham W, Mat Saad A, Alsaigh L, et al. Prognostic factors and survival rate of osteosarcoma: A single-institution study. Asia-Pacific J Clin Oncol. 2015;13.

Sun H-H, Chen X-Y, Cui J, Zhou Z-M, Guo K-J. Prognostic factors to survival of patients with chondroblastic osteosarcoma. Medicine. 2018;97:e12636.

Vasquez L, Tarrillo F, Oscanoa M, et al. Analysis of prognostic factors in high-grade osteosarcoma of the extremities in children: A 15-year single-institution experience. Front Oncol [Internet]. 2016 Feb 2 [cited 2020 Jan 29];6. Available from:

Szendroi M, Pápai Z, Koós R, Illés T. Limb-saving surgery, survival, and prognostic factors for osteosarcoma: the Hungarian experience. J Surg Oncol. 2000;73(2):87–94.

Hu J, Zhang C, Zhu K, et al. Treatment-related prognostic factors in managing osteosarcoma around the knee with limb salvage surgery: A lesson from a long-term follow-up study [Internet]. BioMed Research International. 2019 [cited 2020 Jan 26]. Available from:

Thapa J. Histological assessment of the effect of neoadjuvant chemotherapy on conventional high grade osteosarcoma of the long bones. J Pathol Nep. 1970;1(1):60–2.

García-Castellano JM, Atallah Yordi N, Reyes C, Healey JH. Histopathologic and radiologic assessment of chemotherapeutic response in Ewing’s sarcoma: A Review [Internet]. Sarcoma. 2012 [cited 2020 Jan 30]. Available from:

Harrison DJ, Schwartz CL. Osteogenic sarcoma: Systemic chemotherapy options for localized disease. Curr Treat Options in Oncol. 2017;18(4):24.

Lewis I, Nooij M, Whelan J, et al. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: A randomized phase III trial of the European Osteosarcoma Intergroup. J Nat Cancer Institute. 2007;99:112–28.

Rodriguez-Galindo C, Shah N, McCarville MB, et al. Outcome after local recurrence of osteosarcoma: the St. Jude Children’s Research Hospital experience (1970-2000). Cancer. 2004;100(9):1928–35.

Sha J, Qi W-X, Hu H, Sun Y, Shen Z, Yao Y. Retrospective analysis of prognostic factors for sixty osteosarcoma patients with local recurrence. Chinese-German J Clin Oncol. 2013;12.

Bacci G, Ferrari S, Mercuri M, et al. Predictive factors for local recurrence in osteosarcoma 540 patients with extremity tumors followed for minimum 2.5 years after neoadjuvant chemotherapy. Acta Orthopaedica Scandinavica. 1998;69(3):230–6.

Kempf-Bielack B, Bielack SS, Jürgens H, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005;23(3):559–68.

Mao J, Zhu T, Xie T, et al. Time to relapse predicts post-relapse survival in recurrent osteosarcoma: A meta-analysis. 2016;9:10856–64.

Loh AHP, Navid F, Wang C, et al. Management of local recurrence of pediatric osteosarcoma following limb-sparing surgery. Ann Surg Oncol. 2014;21(6):1948–55.

Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006;106(5):1154–61.

Suryanta VHP, Budi MNS. Management of local soft tissue recurrent osteosarcoma after wide resection and reconstruction with megaprosthesis: A case report. Indones J Cancer. 2019;13(4):137–9.

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