Secondary leukaemia after testicular germ cell tumour treatment: a systematic review and meta‐analysis

BACKGROUND: Testicular germ cell tumours (TGCTs) are the most common malignancy in men aged 15-35 years. Management options for men with TGCTs include surgery, radiation and/or chemotherapy, depending on stage. 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 leukaemia. METHODS: 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 secondary malignant neoplasms in patients following treatment for TGCTs were identified. Our primary outcome was the diagnosis of any leukaemia following treatment, compared to the general population. Meta-analyses were performed using random-effects models, with outcomes reported as standardised incidence ratios (SIRs). Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Six studies including 57 365 patients with 163 secondary leukaemias were included. The weighted-mean follow-up was 12.8 years. The incidence of leukaemia following definitive treatment of TGCTs varied by treatment modality. Chemotherapy was associated with an increase in risk (SIR 5.77, 95% confidence interval [CI] 1.35-24.62; P = 0.03), whereas radiation showed no statistically significant association (SIR 2.55, 95% CI 0.70-9.32; P = 0.11). The certainty of evidence was graded as moderate using the GRADE framework. CONCLUSIONS: Chemotherapy is associated with an increase in the relative risk of secondary leukaemias after treatment of TGCTs, although the absolute risk remains small.