Previous reports have provided direct or indirect evidence that the microbiome plays a role in bladder cancer pathobiology and response to treatment.2 For instance, recent administration of antibiotics, which alters microbiome composition, has been shown to diminish the success of immunotherapy in bladder cancer patients.3,4 Moreover, differences in the urinary and gut microbiome between patients and healthy subjects have been reported by several groups, in different disease stages and populations.2,5-7
In this framework, we characterized the gut microbiome in a cohort of patients enrolled in the PURE-01 clinical trial (NCT02736266), testing the anti-PD-1 compound pembrolizumab as single-agent neoadjuvant therapy in patients with T2–4N0M0 muscle invasive bladder cancer (MIBC).8 We identified specific bacterial taxa associated with treatment outcomes, notably the presence of Sutterella correlating with a positive response, and Ruminococcus bromii with a lack of response. These findings were also supported by data from an in vivo model of bladder cancer, suggesting the potential of gut microbiome profiling as a biomarker to predict immunotherapy efficacy in MIBC.
This study is groundbreaking because it opens the door to using information about our stool bacteria to predict how well cancer treatments might work. This could lead to more personalized and effective treatment plans. Further research is necessary to confirm these findings and to unravel how the microbiome influences immunotherapy results. Nevertheless, our work is a step towards understanding the complex ways our body's unique bacterial microenvironments interact with medical treatments, particularly in cancer therapy.
Written by: Filippo Pederzoli, MD, PhD,1-3 Andrea Necchi, MD,1,2 Massimo Alfano, PhD1
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- Università Vita-Salute San Raffaele, Milan, Italy
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, US
- Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. Cancer Cell 33, 570-580 (2018).
- Pederzoli F, Murdica V, Salonia A, Alfano M. The Gut and Urinary Microbiota: A Rising Biomarker in Genitourinary Malignancies. In: Neoadjuvant Immunotherapy Treatment of Localized Genitourinary Cancers: Multidisciplinary Management (eds Necchi A, Spiess PE). Springer International Publishing (2022).
- Pederzoli F, et al. Is There a Detrimental Effect of Antibiotic Therapy in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Pembrolizumab? Eur Urol 80, 319-322 (2021).
- Hopkins AM, Kichenadasse G, Karapetis CS, Rowland A, Sorich MJ. Concomitant Antibiotic Use and Survival in Urothelial Carcinoma Treated with Atezolizumab. Eur Urol 78, 540-543 (2020).
- Pederzoli F, et al. Sex-specific Alterations in the Urinary and Tissue Microbiome in Therapy-naïve Urothelial Bladder Cancer Patients. Eur Urol Oncol 3, 784-788 (2020).
- Bučević Popović V, Šitum M, Chow CT, Chan LS, Roje B, Terzić J. The urinary microbiome associated with bladder cancer. Sci Rep 8, 12157 (2018).
- Wu P, et al. Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China. Front Cell Infect Microbiol 8, 167 (2018).
- Pederzoli F, et al. Stool Microbiome Signature Associated with Response to Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Cancer. Eur Urol, (2024).