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Simple Summary: Androgen receptor signaling is an important target to investigate in urothelial carcinoma of the bladder because basic and clinical evidence strongly suggests that the androgen receptor is involved in bladder carcinogenesis. Moreover, androgen receptor signaling may suppress anti-tumor immunity. These factors may also be important contributors to the strong male sex bias in urothelial carcinoma of the bladder. Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development. The roles of the androgen receptor in bladder carcinogenesis have obvious implications for understanding the strong male sex bias in this disease and for potential therapeutic strategies as well. In this review, we summarize what is known about androgen receptor signaling in urothelial carcinoma as well as in tumor-infiltrating immune cells, reviewing preclinical and clinical data. We also highlight clinical trial efforts in this area. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers arising from the liver and the biliary tract are aggressive and have limited treatment options. The recent success of immunotherapy where in patient's immune system is activated to fight the tumor is encouraging, but only a fraction of patients with liver cancer remain eligible for this treatment. There is a good pre-clinical evidence (from animal studies) that combination with high-dose focused radiation or stereotactic body radiation (SBRT) makes immunotherapy more effective in these cancers. In this review the available evidence for such combination in treating biliary tract and liver cancers was explored in depth. The preliminary evidence suggests that combining SBRT and immunotherapy is safe and there is a need for large scale trials to investigate its efficacy. The combination of stereotactic body radiation therapy (SBRT) plus immune checkpoint inhibitors (ICI) must be explored to treat advanced primary liver tumors such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Limited retrospective reviews and case reports/series suggest this combination can be effective and safe in both cancer types. With ICIs moving into the first line (IMbrave 150, HIMALAYA, and TOPAZ-1) to manage these cancers, identifying a suitable population for this approach is challenging. Patients with macrovascular invasion (MVI)-positive HCC (especially if larger veins are involved) or recurrent HCCs post-locoregional therapies (such as transarterial radioembolization (TARE), transarterial chemoembolization (TACE), or ablation), as well as those ineligible for bevacizumab or tyrosine kinase inhibitors (TKIs), should be the focus of exploring this combination in HCC. Unresectable or oligometastatic CCA patients who cannot tolerate gemcitabine/cisplatin (GC) or those who progressed on GC without durvalumab and do not have targetable mutations could also be considered for this approach. In both HCC and CCA disease groups, SBRT plus ICI can be examined post-ICI as these two modalities act synergistically to enhance anti-tumor activity (based on pre-clinical studies). Large-scale randomized trials are needed to identify the subsets of primary liver cancers suitable for this approach and to clearly define its clinical benefit. [ABSTRACT FROM AUTHOR]