Secondary malignancies after treatment of testicular germ cell tumors: a systematic review and meta-analysis

Testicular germ cell tumors (TGCTs) are the most common malignancy in men 15-35 years of age. Management options for men with TGCTs include surgery, radiation, and/or chemotherapy. Given TGCTs' excellent survival, most patients live long enough to experience delayed treatment toxicities, warranting careful consideration of therapeutic decisions. An important outcome of interest is the development of secondary malignant neoplasms (SMNs).

A systematic literature search was conducted through a combination of database searches (Medline, EMBASE, and Cochrane library) and manual review. Studies evaluating the incidence of SMNs in patients following treatment for TGCTs were identified. Our primary outcome was the diagnosis of any non-germ cell SMN following treatment, compared with the general population. Meta-analyses were performed using random-effects models, with outcomes reported as standardized incidence ratios (SIRs). Strength of evidence was evaluated using the GRADE framework.

Twenty-one studies including 88 863 patients with 5180 SMNs were included. Median follow-up was 12.5 years. The incidence of non-germ cell SMNs following definitive treatment of TGCTs varied by treatment modality. Surgery alone was not associated with an increased risk (SIR = 0.99, 95% confidence interval [CI] = 0.84 to 1.17); radiation (SIR = 1.66, 95% CI = 1.43 to 1.93), chemotherapy (SIR = 1.65, 95% CI = 1.39 to 1.96), and combined chemotherapy and radiation (SIR = 2.73, 95% CI = 2.23 to 3.33) were associated with a moderate to large increase in risk. There was low to moderate certainty in quality of evidence by GRADE framework.

Chemotherapy, radiation, and their combination are associated with an increased risk of non-germ cell SMNs after the treatment of TGCTs.