The Microbiome and Genitourinary Cancer: A Collaborative Review

Abstract

Context: The recent discovery of the existence of a human genitourinary microbiome has led to the investigation of its role in mediating the pathogenesis of genitourinary malignancies, including bladder, kidney, and prostate cancers. Furthermore, although it is largely recognized that members of the gastrointestinal microbiota are actively involved in drug metabolism, new studies demonstrate additional roles and the potential necessity of the gastrointestinal microbiota in dictating cancer treatment response.

Objective: To summarize the current evidence of a mechanistic role for the genitourinary and gastrointestinal microbiome in genitourinary cancer initiation and treatment response.

Evidence acquisition: We conducted a literature search up to October 2018. Search terms included microbiome, microbiota, urinary microbiome, bladder cancer, urothelial carcinoma, renal cell carcinoma, kidney cancer, testicular cancer, and prostate cancer.

Evidence synthesis: There is preliminary evidence to implicate the members of the genitourinary microbiota as causative factors or cofactors in genitourinary malignancy. Likewise, the current evidence for gastrointestinal microbes in dictating cancer treatment response is mainly correlative; however, we provide examples where therapeutic agents used for the treatment of genitourinary cancers are affected by the human-associated microbiota, or vice versa. Clinical trials, such as fecal microbiota transplant to increase the efficacy of immunotherapy, are currently underway.

Conclusions: The role of the microbiome in genitourinary cancer is an emerging field that merits further studies. Translating microbiome research into clinical action will require incorporation of microbiome surveillance into ongoing and future clinical trials as well as expansion of studies to include metagenomic sequencing and metabolomics.

Patient summary: This review covers recent evidence that microbial populations that reside in the genitourinary tract-and were previously not known to exist-may influence the development of genitourinary malignancies including bladder, kidney, and prostate cancers. Furthermore, microbial populations that exist at sites outside of the genitourinary tract, such as those that reside in our gut, may influence cancer development and/or treatment response.

Keywords: Bladder cancer; Immunotherapy; Kidney cancer; Microbiome; Prostate cancer.

Fig. 1 –

Examples of potential direct interactions between the urinary microbiota and the development of genitourinary cancer. There is a long-recognized association between chronic bladder infection with S. haematobium and the subsequent development of bladder squamous cell carcinoma in both men and women. However, not everyone afflicted with schistosomiasis develops bladder cancer. The presence of species of bacteria such as Staphylococcus albus, Proteus mirabilis, Escherichia coli, and Klebsiella spp. that can mediate the formation of carcinogenic N-nitrosamines as part of the urinary microbiota may contribute to schistosomiasis-induced bladder cancer. Likewise, in prostate cancer, infection of the prostate with proinflammatory bacteria originating from the urinary tract is proposed to contribute to the development of a prostate cancer risk factor lesion termed proliferative inflammatory atrophy. Copyright 2018, Johns Hopkins University, by Lydia Gregg.

Fig. 2 –

Examples of interactions between the gastrointestinal (GI) microbiota and cancer therapies. Cancer therapies, such as chemotherapy, can have a bacteriostatic effect on the GI microbiota, leading to GI microbial dysbiosis and the outgrowth of pathogenic species. This pathogenic outgrowth can lead to systemic effects, such as the production of proinflammatory cytokines that influence tumor growth. The GI microbiota is likewise implicated in the metabolism and inactivation of cancer therapies both in the GI tract and locally within the tumor if there is a bacterial presence. Finally, reactivation of therapies by the GI microbiota locally within the GI tract can lead to treatment-related drug toxicities, including severe diarrhea. Copyright 2018, Johns Hopkins University, by Lydia Gregg.