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Background and objective <p>Metastatic renal cell carcinoma (mRCC) treatment with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor–tyrosine kinase inhibitors (VEGF-TKIs) yields durable benefit in a subset of patients, yet primary resistance remains frequent. Emerging data implicate the gut microbiome as a determining factor of systemic therapy efficacy. This review systematically evaluates clinical evidence on antibiotics (ATBs), probiotics, dietary interventions, and fecal microbiota transplantation (FMT) in modulating the gut microbiome to influence outcomes in adult patients with mRCC.</p> Methods <p>Eligible studies included adult (≥ 18&#xa0;year) RCC cohorts receiving microbiome interventions versus standard care, reporting objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or immune-related adverse events (irAEs).</p> Key findings and limitations <p>Six studies (<i>N</i> = 4738) met criteria: three retrospective cohorts linking peri-ICI ATB exposure to inferior ORR (12.9–34.8%), shorter PFS (hazard ratios [HR] 1.96–3.10), and OS (HR 3.5); one prospective RCT (<i>n</i> = 20) demonstrating engraftment of <i>Bifidobacterium animalis</i> yogurt during VEGF-TKI therapy with enrichment of <i>Akkermansia muciniphila</i> and trends to longer PFS; and one phase II RCT abstract (<i>n</i> = 50) showing FMT from an ICI responder improved 1-year PFS (66.7% vs. 35.0%, <i>p</i> = 0.036) and ORR (54% vs. 28%) in pembrolizumab + axitinib recipients.</p> Conclusions and clinical implications <p>ATB-induced dysbiosis compromises ICI efficacy in mRCC; probiotics and FMT exhibit promise to augment immunotherapy and targeted therapy. Prospective, biomarker-driven RCTs with standardized microbiome assays are needed before routine clinical implementation.</p>

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Gut microbiome impact on systemic therapy outcomes in metastatic renal cell carcinoma: a systematic review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月12日

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  • Filippo Gavi,
  • Martina Bracco,
  • Nicoletta Testori,
  • Francesco Rossi,
  • Daniele Fettucciari,
  • Enrico Panio,
  • Simone Assumma,
  • Pierluigi Russo,
  • Carlo Gandi,
  • Nazario Foschi,
  • Mauro Ragonese,
  • Filippo Turri,
  • Riccardo Bientinesi,
  • Giuseppe Palermo,
  • Chiara Ciccarese,
  • Roberto Iacovelli,
  • Paul T. Kröner,
  • Antonio Gasbarrini,
  • Maria Chiara Sighinolfi,
  • Bernardo Rocco

摘要

Background and objective

Metastatic renal cell carcinoma (mRCC) treatment with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor–tyrosine kinase inhibitors (VEGF-TKIs) yields durable benefit in a subset of patients, yet primary resistance remains frequent. Emerging data implicate the gut microbiome as a determining factor of systemic therapy efficacy. This review systematically evaluates clinical evidence on antibiotics (ATBs), probiotics, dietary interventions, and fecal microbiota transplantation (FMT) in modulating the gut microbiome to influence outcomes in adult patients with mRCC.

Methods

Eligible studies included adult (≥ 18 year) RCC cohorts receiving microbiome interventions versus standard care, reporting objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or immune-related adverse events (irAEs).

Key findings and limitations

Six studies (N = 4738) met criteria: three retrospective cohorts linking peri-ICI ATB exposure to inferior ORR (12.9–34.8%), shorter PFS (hazard ratios [HR] 1.96–3.10), and OS (HR 3.5); one prospective RCT (n = 20) demonstrating engraftment of Bifidobacterium animalis yogurt during VEGF-TKI therapy with enrichment of Akkermansia muciniphila and trends to longer PFS; and one phase II RCT abstract (n = 50) showing FMT from an ICI responder improved 1-year PFS (66.7% vs. 35.0%, p = 0.036) and ORR (54% vs. 28%) in pembrolizumab + axitinib recipients.

Conclusions and clinical implications

ATB-induced dysbiosis compromises ICI efficacy in mRCC; probiotics and FMT exhibit promise to augment immunotherapy and targeted therapy. Prospective, biomarker-driven RCTs with standardized microbiome assays are needed before routine clinical implementation.