Presentation Authors: Nathan C. Wong*, Shawn Dason, Lucas W. Dean, Sumit Isharwal, Mark T.A. Donoghue, Liwei Jia, William D. Tap, Gabriella Joseph, Samuel Funt, Deaglan McHugh, Hikmat A. Al-Ahmadie, Victor E. Reuter, Robert J. Motzer, George J. Bosl, Joel Sheinfeld, David B. Solit, Darren R. Feldman, New York, NY
Introduction: Late relapse (>2 years) germ cell tumor (GCT) is associated with an increased rate of secondary somatic malignancy (SSM). We report our experience with SSM in the setting of late relapse and determine predictors of overall survival (OS).
Methods: From 1985 to 2018, 46 patients with GCT and SSM at late relapse were identified. Clinical and pathologic parameters were reviewed. The Kaplan-Meier method was used to estimate OS from time of late relapse and a Cox proportional hazards model to assess predictors of OS.
Results: Of 46 men (44 testicular primary, 2 mediastinal primary), median time to late relapse with SSM was 10.4 years (range, 2.3 to 38.1 years). Most (n=27, 59%) were symptomatic at presentation but 11 were detected by elevated tumor markers (AFP 8, HCG 2, both 1) and 8 by surveillance imaging. SSMs were predominately adenocarcinoma (25), sarcoma (14), poorly differentiated neoplasm (3), Wilms tumor (2), primitive neuroectodermal tumor (PNET) (1) and glioma (1). Median time to relapse was longer for adenocarcinoma vs other histotypes of SSM (14.6 vs 4.1 years, p < 0.001). The initial site of relapse was the retroperitoneum (RP, 26), pelvis (7), lung (6), retrocrural space (3), mediastinum (2), neck (1) and duodenum (1). Only 10 of 26 men with late relapse in the RP had undergone prior retroperitoneal lymph node dissection (RPLND) (all at outside institutions; variable templates) with histology in 7/10 showing teratoma. The other 16 men had received chemotherapy only (8), orchiectomy only for stage I (3), RPLND aborted due to cardiac arrest (1), and unknown (4). All 46 late relapses were managed with surgical resection; 26 also received chemotherapy (16 SSM-directed, 10 GCT-directed). Overall, 12 patients died and the median OS was 14.2 years. On univariable analysis, symptomatic presentation (HR = 3.1), SSM at multiple sites (HR = 3.9), extra-RP disease (HR: 3.9), and incomplete/no resection of SSM (HR = 3.6) predicted mortality. On multivariable analysis, only extra-RP disease (HR = 4.8) was independently associated with inferior OS (5-year OS, 82% v 52%, p = 0.017).
Conclusions: SSM is an important potential complication of late relapse GCT and seems to be associated with the lack of resection of retroperitoneal metastases. Early identification and complete surgical resection prior to SSM arising in extra-RP sites is critical to optimizing outcomes.
Source of Funding: This research was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers and funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.