Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma.

Background: The authors present the long-term follow-up (>25 years) data from 1 of the original prospective, randomized trials that compared adjuvant chemotherapy with expectant management in patients with high-grade, localized osteosarcoma. In addition, the value of pathologic necrosis induced by a single cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease-free and overall survival.

Methods: Fifty-nine patients with high-grade, localized osteosarcoma were enrolled in a prospective trial that was performed between 1981 and 1984 at the University of California-Los Angeles (UCLA). Patients were randomized to receive either adjuvant chemotherapy or observation after surgical resection. Long-term outcomes, follow-up, and pathologic review of all available histologic sections were performed.

Results: The 25-year disease-free survival rate was 28% for patients who received adjuvant chemotherapy compared with 15% for the untreated patients (P = .02). The overall survival rate at 25 years was also significantly higher for treated patients versus untreated patients (38% vs 15%; P = .02). Tumor necrosis >90% after a single round of chemotherapy was a statistically significant predictor of overall survival and disease-free survival for patients who received adjuvant therapy (164 months vs 65 months [P = .04] and 141 months vs 14 months [P < .01], respectively).

Conclusions: Patients with high-grade, localized osteosarcoma who received adjuvant chemotherapy after undergoing definitive surgical resection had a statistically significant benefit in disease-free and overall survival that was maintained through 25 years. Tumor necrosis after just 1 cycle of neoadjuvant chemotherapy and radiation was predictive of overall survival and disease-free survival in patients who received adjuvant chemotherapy.