Standard-Dose Versus High-Dose Cisplatin for Intermediate/Poor-Risk Extracranial Malignant Germ Cell Tumors: Re-Analysis of Pediatric Oncology Group 9049 and Children's Cancer Group 8882 Trial Using Updated MaGIC Risk Stratification.

Abstract

Background: Cisplatin, etoposide, and bleomycin (PEb) have been the standard of care for patients with germ cell tumors (GCT). In the 1990s, an intergroup trial (POG9049/CCG8882) randomized patients with high-risk GCT, as defined by the 1990 criteria, to high-dose (HDPEb) versus standard-dose PEb. HDPEb resulted in improved event-free survival (EFS), but no difference in overall survival (OS), thus standard-dose PEb has remained the standard of care. Subsequently, the Malignant Germ Cell International Consortium (MaGIC) updated the risk stratification for pediatric and adolescent patients with GCT. Currently, patients are categorized as intermediate or poor risk if they are ≥11 years of age with Stage IV ovarian GCT, or testicular, mediastinal, or retroperitoneal GCT with intermediate or poor prognosis using the International Germ Cell Consensus Classification criteria.

Methods: We re-analyzed data from the POG9049/CCG8882 trial using the updated MaGIC risk stratification to determine whether HDPEb improved outcomes over PEb in patients with intermediate/poor-risk GCTs.

Results: Among 299 patients in the trial, 57 patients (48 males, nine females) met the inclusion criteria for this analysis. There were no statistically significant differences in 5-year EFS (0.72 vs. 0.70, p-value = 0.82) or OS (0.76 vs. 0.74, p-value = 0.91) among patients treated with HDPEb versus PEb, respectively. Also, of note patients with mediastinal primaries had significantly worse 5-year EFS (0.51 vs. 0.83, p-value = 0.0062) and OS (0.49 vs. 0.89, p-value = 0.0013) compared to other sites, with no difference in outcome between HDPEb and PEb.

Conclusions: Treatment with HDPEb did not improve outcomes for intermediate/poor-risk GCT patients compared to standard-dose PEb.