One LSR investigated the effect of adjuvant tyrosine kinase inhibitors (TKIs) on the risk of cancer recurrence and progression to metastases in high-risk renal cell carcinoma.9 The review started in 2018 and was retired from a living mode in 2021. Meta-analysis showed that adjuvant TKIs as compared with observation offered no benefit in overall survival or disease-free survival and significantly increased adverse events. The termination was based on two triggers, conclusiveness of evidence based on certainty of the evidence and on statistical considerations, and relevance to stakeholders (box 1).

1. Evidence was judged to be conclusive.

a. Certainty of evidence.

The certainty in evidence using the GRADE approach was judged to be high for the most important outcomes of overall survival, disease-free survival and all-cause grade 3 or above adverse effects. Data were derived from five randomised controlled trials that were judged to be at low risk of bias. There were no concerns about inconsistency, indirectness or evidence of publication bias.

b. Statistical considerations:

Trial sequential analysis (TSA) suggested that the evidence was statistically conclusive. For example, figure 1 for the outcome of overall survival shows TSA with the Z score ending in the futility region, suggesting that further studies will unlikely show a meaningfully different treatment effect. This analysis was based on data from 6531 patients, which exceeded the optimal information size of 5492, which is a sample size calculation based on an assumed type 1 error rate of 5%, power of 80% (ie, type 2 error rate of 20%) and a conservative 15% plausible relative risk reduction (higher relative risk reductions of 20%–30% are more commonly used17 but would lead to a smaller optimal information size).

2. Relevance-based considerations

Most practitioners do not currently consider adjuvant TKIs in clinical practice due to perceived lack of survival benefit and high incidence of toxicity. The contemporary trials are now focused on the use of immune checkpoint inhibitors in this setting; for which the evidence is increasing and qualifies for an LSR.