Adjuvant Systemic Therapies After Nephrectomy for Renal Cell Carcinoma: A Bayesian Network Meta-Analysis and Multi-Criteria Benefit-Risk Assessment.

Authors

Shugo Yajima, Gaku Okumura, Soichiro Yoshida, Hiroshi Fukushima, Hiroyuki Sato, Akihiro Hirakawa, Toshiki Kijima, Hitoshi Masuda, Yasuhisa Fujii

Published in

Targeted oncology. Oct 18, 2026. Epub Oct 18, 2026.

Abstract

Adjuvant pembrolizumab has improved disease-free survival after nephrectomy for high-risk renal cell carcinoma, and pembrolizumab plus belzutifan has further expanded the treatment landscape.
We compared efficacy and treatment burden across adjuvant systemic therapies and examined the benefit-risk trade-off of the combination.
Randomized trials of systemic therapy after nephrectomy were synthesized using a Bayesian network meta-analysis. Disease-free survival hazard ratios were converted to illustrative 2-year estimates using a common pembrolizumab baseline. Observed differences in 2-year disease-free survival, grade 3 or higher adverse events, and treatment discontinuation came from LITESPARK-022. Using these data, a multi-criteria decision analysis examined how outcome weighting affected the balance between the two regimens.
Six randomized datasets formed a tree-shaped network of eight regimens. In LITESPARK-022, adding belzutifan yielded approximately seven additional disease-free patients per 100 treated, but also approximately 22 additional patients with grade 3 or higher adverse events and 15 additional treatment discontinuations. Under the primary decision-analytic assumptions, the combination had the higher net-benefit score only when disease-free survival received roughly two thirds of the decision weight (threshold 0.68; range 0.47-0.79 across sensitivity analyses). Most comparisons relied on a single dataset, and overall survival and patient-reported outcomes remained immature.
Adding belzutifan to pembrolizumab improved disease-free survival but increased toxicity and treatment discontinuation. The decision analysis illustrates a model-dependent trade-off rather than identifying a preferred regimen. Because overall survival data are immature, the decision to intensify treatment remains risk and preference sensitive.
CRD420261454205.

PMID:
42892667
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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