Systematic review and meta-analysis of secondary malignancies after treatment of testicular germ cell tumors

Given the excellent survival of testicular germ cell tumors (TGCTs), most patients live long enough to experience delayed treatment toxicities, such as the development of secondary malignant neoplasms (SMNs). Systematic review and meta-analysis of 21 studies including 88,863 TGCT patients found that with median follow-up of 12.5 years, 5,180 survivors developed a non-germ cell SMN. The incidence of non-germ cell SMNs after definitive treatment of TGCTs varied by treatment modality. Compared with the general population the risk of developing a non-germ cell SMN was not increased after surgery alone (SIR 0.99; 95% CI 0.84-1.17) but was increased after radiation (1.66; 1.43-1.93), chemotherapy (1.65; 1.39-1.96), and combined radiation and chemotherapy (2.73; 2.23-3.33). There was low to moderate certainty in quality of evidence by GRADE framework. The authors conclude that radiation, chemotherapy, and their combination for TGCTs are associated with an increased risk of developing non-germ cell SMNs.