What is the best clinical approach to recurrent/refractory osteosarcoma?

ABSTRACT

Introduction: Osteosarcoma is the most common malignant bone tumor. It is currently treated with pre-and postoperative chemotherapy, associated with surgical resection of the tumor.

Area covered: Relapses occur in about one in three patients presenting with localized disease, and three in four of those with metastases at diagnosis. Relapsing disease carries a very poor prognosis, with 5-year survival rates ranging between 13% and 40%.

Expert opinion: Patients with unilateral lung involvement or solitary lung metastases and a recurrence-free interval (RFI) longer than 24 months have a better prognosis, and could be managed with surgical resection and close observation. Complete surgical resection of all sites of disease remains essential to survival: patients unable to achieve complete remission have a catastrophic overall survival rate. The role of second-line chemotherapy is not at all clear, and no controlled studies are available on this topic. It is worth considering for patients unable to achieve complete surgical remission, and those with multiple metastases and/or a RFI <24 months. Given their dismal prognosis, patients with multiple sites of disease not amenable to complete surgical resection should also be considered for innovative therapeutic approaches.

KEYWORDS:

• Osteosarcoma
• relapse
• surgery
• chemotherapy
• different patterns of disease
• targeted drugs

Article highlights

• Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents.

• The disease relapses in approximately one in three patients with localized disease at presentation, and three in four of those with metastases at the time of their diagnosis.

• Patients with unilateral lung involvement or solitary lung metastases and an RFI of more than 24 months carry a better prognosis than patients with bilateral lung metastases or multiple sites of spread and a shorter RFI, and could be managed with surgical resection and close observation.

• The role of second-line chemotherapy for relapsing patients remains to be seen, and no controlled studies are available on this topic.

• Chemotherapy should be considered for patients unable to achieve complete surgical remission, and for those with multiple metastases and/or a short RFI (<24 months).

• Ifosfamide, with or without etoposide, and gemcitabine with docetaxel have been widely used for patients with recurrent OS; no new drugs have been FDA- or EMA-approved in the last 25 years.

• Complete surgical resection of all sites of disease remains predictive of and essential to survival. The overall survival rate for patients unable to achieve complete surgical remission is very poor, ranging from 0% to 8%. Repeated metastasectomies can prolong survival and even cure some patients.

• Radiotherapy may be an option in some cases, with a view to achieving a cure or prolonging survival and local control, or for palliation of symptomatic metastases.

• Patients with multiple sites of disease not amenable to complete surgical removal should be considered for innovative therapeutic approaches.

• Collaborative efforts to improve our understanding of the biology of OS, and the use of preclinical models to test novel agents will be crucial to the identification of ways to improve patient outcomes.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

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