Second-Line Chemotherapy in Patients With Relapsed Extragonadal Nonseminomatous Germ Cell Tumors: Results of an International Multicenter Analysis

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Abstract
PURPOSE: Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with identical salvage chemotherapy regimens, as are patients with metastatic testicular cancer. This investigation evaluates the results of second-line chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors for survival. PATIENTS AND METHODS: We conducted a retrospective review of 142 patients treated at eleven European and American centers between 1975 and 1996. All had received cisplatin-containing regimens as induction treatment. RESULTS: Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary mediastinal and 30% of patients with primary retroperitoneal disease. Median follow-up since start of salvage treatment was 11 months (range, 1 to 157) for all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight patients (34%) received high dose chemotherapy with autologous bone marrow transplant at relapse, and 10 of these patients (21%) are continuously disease-free. Primary mediastinal location (P = .003), sensitivity to cisplatin (P = .003), elevated β-HCG at relapse (P = .04), and normal LDH at diagnosis (P = .01) were shown to be significant negative prognostic factors for overall survival in univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1 to 5.2] were significant negative prognostic factors in multivariate analysis. CONCLUSION: Although current salvage strategies will cure between 20% and 50% of recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients appear to have an inferior survival rate, in particular in case of primary mediastinal location. Mediastinal primary tumor and inadequate response to cisplatin-based induction chemotherapy have been identified as independent negative prognostic factors, both associated with an approximately two-fold higher risk for failure of salvage treatment.