A Randomized Trial of Bicalutamide in Non-Muscle Invasive Bladder Cancer

Prior treatment

• Participants who have had a previous exposure to sex hormone (e.g., exogenous androgens) or anti-androgenic therapies (e.g., luteinizing hormone-releasing hormone \[LHRH\] agonists, LHRH antagonists, 5 alpha reductase-inhibitors, abiraterone or other anti-androgens) within 6 months of accrual
• Participants taking Coumarin derivative anticoagulation (e.g., warfarin). Other anticoagulation medications are allowed.
• Participants receiving any other investigational agents.
• History of prior or concurrent muscle invading UC, or concurrent prostatic urethral, urethral, or upper tract UC or non-urothelial bladder cancer
• Participants who have received Gacillus Calmette-Guerin (BCG) within 2 years are not eligible.

Other illness

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bicalutamide.
• History of radiation therapy to the pelvis, prostate or prostatic bed, or rectum
• Any condition (uncontrolled intercurrent illness, psychiatric illness, or social situation) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Allergy or hypersensitivity to bicalutamide, or excipients, unable or unwilling to take ADT.
• Participants with suspected Carcinoma in Situ (CIS) without suspected Ta or T1 disease are not eligible.
• Participants with a history of documented CIS within 2 years are not eligible.

Other

• Plans to father a child while enrolled in this study or within 4 months after the last dose of study intervention.

• Biologic male adults (\>= 18 years old)
  • Note: Because no dosing or adverse event (AE) data are currently available on the use of bicalutamide in participants \< 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
• Have suspected new or occasionally recurrent NMIBC (i.e., \</= 2 prior NMIBC episodes in the 18 months preceding the cystoscopy where the index tumor was identified) on clinic-based cystoscopy or imaging as viewed by an American Urological Association (AUA) board-certified urologist
• Have had cross sectional imaging of the abdomen and pelvis (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] with or without contrast) within 6 months prior to enrollment with no signs of upper tract urothelial cancer (UC), invasive, nor metastatic disease
  • Note: If adenopathy or upper tract abnormalities are identified, a negative biopsy and or ureteroscopy is required prior to enrollment
• Participants with single and multiple tumor lesions
• In the opinion of the treating urologist, the participant is suitable to undergo surgery.
• Participants may have received intravesical chemotherapy at any time.
• Total bilirubin =\< 1.5 x institutional upper limit of normal (note: in participants with Gilbert's syndrome, if total bilirubin is \> 1.5 x upper limit of normal, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x upper limit of normal, participants may be eligible)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2 × institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2 × institutional upper limit of normal
• Serum Testosterone \>= 250 ng/dL
• Thyroid stimulating hormone (TSH) within institutional normal
• The effects of bicalutamide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men who are having sex must wear a condom when engaging in any activity that allows for passage of ejaculate to another person throughout the course of the study and 4 months after receiving last dose of study intervention. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak. Additionally, men must agree to not donate sperm for the purpose of reproduction during the study and for a minimum of 4 months after receiving the last dose of study intervention
• Ability to understand and the willingness to sign a written informed consent document