Prognostic factors in advanced seminoma: An analysis from the IGCCCG Update Consortium.

Abstract

386 Background: Extrapulmonary visceral metastases were the only adverse prognostic factor among 660 advanced seminomas in the original classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) treated between 1975 and 1990 and published 1997. Outcomes may have improved with current era management and additional prognostic factors may exist. Methods: To update the original IGCCCG classification, an international consortium (30 centers/groups) provided data on 2458 advanced seminoma patients treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2015 in prospective cohorts or clinical trials. Progression-free (PFS) and overall survival (OS) probabilities were calculated. CART analysis was used to identify prognostic factors inside original IGCCCG good risk group to further refine the classification. Among eligible 2302 patients with full data, a training set of 1509 patients (1437 good risk and 72 intermediate risk) was used for model building. An independent set of 793 patients was set aside for validation. Primary endpoints were PFS and OS at 5 years. Results: Compared with the 1997 IGCCCG benchmarks, the 5-year PFS rates increased to 88.7% (87.2 - 89.9%) and 78.4% (69.6 - 84.9%) in good and intermediate IGCCCG patients. The corresponding 5-year OS rates were 95.4% (94.4 - 96.2%) and 87.2% (79.2 - 92.2%). CART analysis identified LDH with a cut-point of 2.5 x ULN as the single most significant prognostic factor in good risk patients with 5-y PFS rates of 92.1% (90.3 - 93.6%) and 79.2% (74.2 - 83.4%) in low and high LDH subgroups. (HR = 2.90, P < .0001). Good risk patients with LDH above 2.5 x ULN (313 of 1411 patients) performed similarly to the intermediate IGCCCG patients; hCG was not independently prognostic. Conclusions: In this modern era series, the original IGCCCG still significantly discriminates between "good” and "intermediate" risk metastatic seminoma, but with significantly improved PFS and OS in both risk groups. LDH at a cut-off point of 2.5 x ULN further refines this classification and identifies men with intermediate risk seminoma in the absence of extrapulmonary visceral metastases. This refinement will be relevant to improve future seminoma care.