Monday July 01, 2019 from 07:30 to 09:00
Clinical features and outcomes of secondary somatic malignancy arising from teratoma in late relapse germ cell tumour
Nathan C. Wong1, Shawn R. Dason1, Lucas Dean1, Sumit Isharwal2, Mark Donoghue3, Liwei Jia4, William Tap5, Gabriella Joseph5, Samuel Funt5, Deaglan McHugh5, Hikmat Al-Ahmadie4, Victor E. Reuter4, Robert J. Motzer5, George J. Bosl5, Joel Sheinfeld1, David B. Solit5, Darren R. Feldman5.
1Department of Surgery, Urology Services, Memorial Sloan Kettering Cancer Center, New York, NY, United States; 2Department of Urology, University of Virginia Health System , Charlottesville, VA, United States; 3Department of Molecular Oncology , Memorial Sloan Kettering Cancer Center, New York, NY, United States; 4Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States; 5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
Introduction: Late relapse (LR) (>2 years) germ cell tumour (GCT) is associated with an increased rate of secondary somatic malignancy (SSM). We report our experience with SSM in the setting of LR and determine predictors of overall survival (OS).
Methods: From 1985–2018, 46 patients with GCT and SSM at LR were identified and underwent chart review. The Kaplan-Meier method was used to estimate OS from time of LR and a Cox proportional hazards model to assess predictors of OS.
Results: Of 46 men (44 testicular primary, two mediastinal), median time to LR with SSM was 10.4 years. Most (n=27) were symptomatic at presentation but 11 were detected by elevated tumour markers and eight by imaging. SSMs were predominately adenocarcinoma (25), sarcoma (14), Wilms tumour (two), primitive neuroectodermal tumor (PNET) (one), and other (four). Median time to LR was longer for adenocarcinoma vs. other histotypes of SSM (14.6 vs. 4.1 years; p<0.001). The initial site of LR was the retroperitoneum (RP, 26), pelvis (seven), lung (six), retrocrural space (three), mediastinum (two), and other (two). Only 10/26 men with LR in the RP had undergone prior retroperitoneal lymph node dissection (RPLND) (all at outside institutions; variable templates) with teratoma in 7/10. The other 16 men had received chemotherapy only (eight), orchiectomy only for stage I (three), RPLND aborted (one), and unknown (four). All LR were managed with surgery; 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 (hazard ratio [HR] 3.1), SSM at multiple sites (HR 3.9), extra-RP disease (HR 3.9), and incomplete resection of SSM (HR 3.6) predicted mortality. On multivariable analysis, only extra-RP disease (HR 4.8) was independently associated with inferior OS (five-year OS 82% vs. 52%; p=0.017).
Conclusions: SSM is an important potential complication of LR GCT and seems to be associated with the lack of resection of RP metastases. Early identification and complete resection prior to SSM arising in extra-RP sites are critical to optimizing outcomes.