Advancements in microbiome research reveal its impact on cancer treatment outcomes, particularly in renal cell carcinoma (RCC). While immune checkpoint inhibitors (ICIs) have improved survival in metastatic RCC, composition of the gut microbiome has the potential to influence their efficacy. Antibiotic-induced microbiome disruptions correlate with diminished outcomes, while strains such as Akkermansia muciniphila, Clostridium butyricum, and others enhance immune responses and progression-free survival. Some prebiotics such as inulin gel can alter the gut flora to overcome the resistant strains occurring in response to immune therapy. This mini-review explores microbiome-targeted interventions, such as pre/probiotics and fecal microbiota transplantation, for overcoming ICI resistance. Although promising, prospective randomized trials are needed to standardize clinical applications and optimize microbiome-targeted treatments. The standard use of gut-modulating therapy cannot be recommended at present outside of clinical trials. A double-blind placebo-controlled randomized trial of ICI ± gut modulating therapy is being planned in frontline therapy of advanced RCC (BIOFRONT trial by the Southwest Oncology Group).
Integrating microbiome research into renal cell carcinoma (RCC) clinical management is an exciting development with significant implications for urologists. As outlined in the mini-review published in European Urology Focus by Elyasa, Barata, and Vaishampayan, the gut microbiome’s composition profoundly influences the efficacy of immune checkpoint inhibitors (ICIs), a cornerstone of metastatic RCC (mRCC) treatment [1].
This emerging knowledge underscores the potential for microbiome modulation to enhance therapeutic responses and overcome resistance.
What does a urologist need to know about the topic? Here are some key points to consider.
The interplay between gut health and RCC outcomes is critical. Disruptions in the microbiome, often induced by antibiotics or proton pump inhibitors, correlate with reduced efficacy of ICIs, highlighting the microbiome's role in modulating systemic immunity. Beneficial bacterial strains like Akkermansia muciniphila and Clostridium butyricum promote cytotoxic T-cell infiltration, enhancing tumour suppression. Conversely, an imbalanced microbiome, marked by harmful strains such as Clostridium hathewayi, can impair ICI efficacy.
Several microbiome-targeted strategies are gaining traction. Probiotics such as C. butyricum and faecal microbiota transplantation have shown promise in improving progression-free survival (PFS) and response rates in mRCC. For instance, a phase 1 trial incorporating C. butyricum into ICI regimens demonstrated significant survival benefits with no additional toxicity. Upcoming trials, such as BIOFRONT and MITRIC, aim to validate these findings, potentially integrating microbiome modulation into routine RCC care.
Dietary interventions provide another approach to optimising the gut microbiome. Prebiotics like inulin gel have demonstrated efficacy in enhancing ICI outcomes in preclinical models, supporting the notion that dietary modulation may be a non-invasive complement to existing treatments.
Microbiome profiling offers a pathway to personalised oncology. By analysing a patient’s gut microbiota, clinicians may predict treatment responses and tailor therapies. This approach aligns with the broader trend of precision medicine, enabling urologists to deliver more targeted, effective care.
Although the results are promising, significant challenges remain. Microbiome composition varies widely among individuals, influenced by factors such as diet, genetics, and prior treatments. Standardising microbiome-targeted therapies across diverse populations requires large-scale, randomised clinical trials. Moreover, while preliminary data are encouraging, routine use of microbiome-modulating agents outside clinical trials is not yet supported.
For urologists, understanding the microbiome’s impact on RCC treatments is essential. Incorporating this knowledge into clinical practice involves staying informed about ongoing trials and emerging therapies. Urologists should also consider the implications of antibiotics and other medications on patients undergoing ICIs. By recognising the microbiome’s role, clinicians can make informed decisions to optimise outcomes.
In conclusion, the microbiome represents a transformative frontier in RCC management, offering new avenues to enhance ICI efficacy and address resistance. As research progresses, microbiome-targeted interventions may become integral to RCC treatment protocols, allowing urologists to offer innovative, patient-centred care. Until then, active participation in clinical trials and multidisciplinary collaboration will be key to advancing this promising field.
Reference
Elyas S, Barata P, Vaishampayan U. Clinical Applications of Microbiome in Renal Cell Carcinoma. Eur Urol Focus. 2025 Jan 16:S2405-4569(24)00264-5. doi: 10.1016/j.euf.2024.12.006. Epub ahead of print. PMID: 39824679.