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© Research
Publication : European urology oncology

Sex Differences in Bladder Cancer Immunobiology and Outcomes: A Collaborative Review with Implications for Treatment.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in European urology oncology - 01 Oct 2020

Koti M, Ingersoll MA, Gupta S, Lam CM, Li X, Kamat AM, Black PC, Siemens DR,

Link to Pubmed [PMID] – 32967818

Link to DOI – S2588-9311(20)30140-110.1016/j.euo.2020.08.013

Eur Urol Oncol 2020 10; 3(5): 622-630

Urothelial carcinoma of the bladder (UCB) exhibits significant sexual dimorphism in the incidence, etiology, and response to intravesical immunotherapy. Environmental factors such as tobacco use and clinical management issues such as delayed presentation have widely been associated with sex differences in UCB outcomes. Emerging findings from immune checkpoint blockade trials are suggestive of differential outcomes in females compared with males. Sex-specific differences in the way immune system functions and responds to pathogenic insults are well established. As such, an in-depth understanding of the genetic and epigenetic factors contributing to sex-associated differences in response to immunomodulatory therapies is needed urgently for improved management of UCB.To review the associations between patient sex and clinical outcomes, with a focus on the incidence, host intrinsic features, and response to therapies in UCB.Using the PubMed database, this narrative review evaluates published findings from mouse model-based and clinical cohort studies to identify factors associated with sex and clinical outcomes in bladder cancer. A scoping review of the key findings on epidemiology, genetic, hormonal, immune physiology, and clinical outcomes was performed to explore potential factors that could have implications in immunomodulatory therapy design.Sex-associated differences in UCB incidence and clinical outcomes are influenced by sex hormones, local bladder resident immune populations, tumor genetics, and bladder microbiome. In the context of therapeutic outcomes, sex differences are prominent in response to bacillus Calmette-Guérin immunotherapy used in the treatment of non-muscle-invasive bladder cancer. Similarly, with respect to tumor molecular profiles in muscle-invasive bladder cancer, tumors from females show enrichment of the basal subtype.Among proposed tumor/host intrinsic factors that may influence response to immune-based therapies, patient sex remains a challenging consideration that deserves further attention. Evidence to date supports a multifactorial origin of sexual dimorphism in the incidence and outcomes of UCB.In this review, we highlight the sex-associated host and tumor intrinsic features that may potentially drive differential disease progression and therapeutic response in urothelial carcinoma of the bladder.

https://pubmed.ncbi.nlm.nih.gov/32967818