Progression after first-line chemotherapy with normal serum tumor markers (STM) in non-seminomatous germ-cell tumors (NSGCT).

Abstract

615 Background: Surveillance of patients with NSGCT following first-line chemotherapy typically relies on a combination of STM and imaging. While STM are sensitive, a proportion of relapses occur without STM elevation. We aimed to characterize the incidence of progression with normal STM in patients with NSGCT who had initial elevated STM prior to first-line chemotherapy. Methods: The Indiana University (IU) germ cell tumor database was reviewed for patients with metastatic NSGCT who had elevated tumor markers prior to first-line chemotherapy (AFP >25 ng/mL or β-hCG >5 mIU/mL) and subsequently had disease progression. Patients with radiographic relapse in the absence of STM were classified as “normal STM relapse.” Clinicopathologic variables, sites of relapse, and histology at progression were compared between elevated and normal STM groups at progression using chi-square or Fisher’s exact test, as appropriate. Results: A total of 725 patients were eligible. Primary tumor site was testis/retroperitoneal in 88.4% and mediastinal in 11.6%. A total of 82 (11.3%) progressed/relapsed with normal STM. Among the 82 patients who progressed with normal STM, sites of progression were lymph nodes in 60 (73.2%), lungs in 44 (53.7%), brain in 11 (13.4%), liver in 6 (7.3%), and bones in 3 (3.7%). Histologic evaluation at relapse revealed similar rates of viable germ cell tumor between patients with normal STM and elevated STM at progression (20.7% vs. 16.5%, p = 0.349). However, teratoma (40.2% vs. 11.8%, p < 0.001) and malignant transformation of teratoma (14.6% vs. 2.6%, p < 0.001) were significantly more common among patients with normal STM relapse. Conclusions: Among patients with metastatic NSGCT who have elevated STM at diagnosis and progress after first-line chemotherapy, a clinically meaningful subset will have radiographic progression with normal STM distinguished by increased prevalence of teratoma and malignant transformation. These findings underscore the role of routine imaging in addition to STM in post-therapy follow-up of NSGCT. Pathology at Progression STM Normal (n = 82) STM Elevated (n = 643) p-value GCT 17 (27.4%) 106 (53.3%) 0.349 Teratoma 33 (53.2%) 76 (38.2%) <0.001 Malignant Transformation 12 (19.4%) 17 (8.5%) <0.001 No Pathology 20 444