Initiation of high dose chemotherapy at rising tumor markers compared with radiographic progression in patients with relapsed germ-cell tumors (GCT).

5033 Background: Patients with GCT who relapse after first-line therapy can be cured with salvage high-dose chemotherapy (HDCT). We evaluate the outcomes of patients who received HDCT based on tumor maker rise only compared to radiographic progression only or both. Methods: The Indiana University Testicular Cancer database was queried for pts with GCT who were treated with salvage HDCT between 2004-2024. 2-yr progression free survival (PFS) and overall survival (OS) were analyzed among subgroups of patients who had tumor markers rise only (group 1) at start of HDCT compared to those who had radiological progression only or both (group 2). The Kaplan-Meier method was used to analyze PFS and OS. Comparisons between groups were done using the log-rank test. Results: 316 pts with GCT treated with salvage HDCT between March 2004 and May 2024 and had detailed information regarding progression leading to HDCT were included. Median age was 32.05 (16-70). Histology was non-seminoma in 237 (75.0%) pts and seminoma in 79 (25.0%) pts. Primary site was testis in 273 (86.4%) pts, retroperitoneum in 20 (6.3%) and mediastinum in 23 (7.3%). 156 (49.4%) pts had IGCCCG good risk disease at diagnosis, 28 (8.9%) had intermediate risk disease, and 132 (41.8%) had poor risk disease. 101 (32.0%) patients were platinum refractory at start of HDCT. HDCT was 2nd line therapy in 264 (83.5%) pts, 3rd line in 49 (15.5%), 4th line in 2 (0.6%) and 5th line in 1 (0.3%). At initiation of HDCT, 98 (31.0%) pts had tumor marker (AFP and/or hCG) rise only, 69 (21.8%) had radiographic progression only, and 149 (47.2%) had both. Median follow-up from start of HDCT was 3.67 years (0.03-19.5). For the overall population, 2-yr PFS was 62.4 with 95% CI (56.7-67.5) and 2-yr OS was 71.9 with 95% CI (66.3-76.8). 60 (59.4%) of patients in group 1 had platinum refractory disease compared to 41 (40.6%) in group 2. 2-yr PFS for group 1 was 44.8% (34.6-54.4%) vs 70.3% (63.6-76%) for group 2 (P<0.001). 2-yr OS was 58.8% (47.5-68.6%) for group 1 vs 77.4% (70.9-82.7%) for group 2 (P=0.001). Conclusions: Patients with relapsed GCT with rising tumor markers only at time of initiation of salvage HDCT had inferior 2-yr PFS and OS likely due to higher rates of platinum refractory disease in this population.