Clinical characteristics and outcomes of metastatic germ cell tumors with highly elevated human chorionic gonadotropin levels.

e17018 Background: Serum human chorionic gonadotropin (hCG) levels greater than 50,000 in the pretreatment assessment of metastatic germ cell tumors (GCT) indicate poor-risk disease with serial levels during and after first-line chemotherapy incorporated into the response assessment. We aimed to describe the natural hCG history and outcomes of poor-risk patients (pts) with highly elevated hCG undergoing first-line treatment. Methods: 48 pts with metastatic GCT and pretreatment hCG >50,000 evaluated at Indiana University between January 1998 and December 2024 were identified with available hCG values during and after completion of first-line chemotherapy. Pts were divided into 3 categories based on post-treatment hCG normalization after completion of first-line chemotherapy: ≤28 days (N=14), >28 days (N=16), and never normalized (N=18). Kaplan-Meier methods were used to analyze progression free survival (PFS) and overall survival (OS). Groups were compared using the log rank test. Results: Median age was 27. Median pretreatment hCG was 217,488 (range, 50,704-1,231,875) and median hCG prior to last chemotherapy cycle was 56 (range, 1-5,029). Of the 48 pts, hCG values in 30 pts continuously declined and normalized with first-line chemotherapy +/- post-chemotherapy surgery. Median time to normalization of hCG after completion of first-line chemotherapy was 39 days (range, 0-174). Twenty-one pts remain continuously disease-free during a median follow-up of 6.1 years. Twelve of 16 pts normalizing their hCG >28 days after completion of chemotherapy remain continuously disease-free. Of the 18 pts who never normalized their hCG with first-line treatment, 8 are currently disease-free after salvage therapy. Conclusions: Patients with hCG levels >50,000 receiving first-line chemotherapy will likely have persistently elevated levels at the start of their final course of chemotherapy. Despite this, a significant portion of patients will not progress and remain disease-free with eventual hCG normalization. Patients with progression by rising hCG remain curable with second-line therapy. Our strategy at Indiana University after completion of first-line chemotherapy with elevated hCG that is declining includes weekly hCG levels as progression will first be identified by rising hCG in most cases. Variable (N) 2-year PFS p-value 2-year OS p-value All pts (48) 49% 88% Time to hCG normalization after first-line chemotherapy- ≤28 days (14)- >28 days (16) 77%81% 0.65 100%93% 0.57 Normalization of hCG after first-line treatment- Yes (30)- No (18) 79%0% <0.0001 96%76% 0.06