Inclusion Criteria:
* Biologic male adults (\>= 18 years old)
* Note: Because no dosing or adverse event (AE) data are currently available on the use of apalutamide in participants \< 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
* Have suspected non-muscle invasive bladder carcinoma (NMIBC) 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
* Newly suspected, diagnosed, or occasionally recurrent bladder cancer (BC)
* Note: Occasional recurrence is defined as =\< 2 prior NMIBC episodes in the 18 months preceding cystoscopy where the index tumor was identified
* Participants with single and multiple tumor lesions
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
* 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
* Urine Culture \< 50,000 colonies/cc of 1 or more organisms (if found and treated and a confirmed negative culture obtained off antibiotics before study drug is started, they will be eligible)
* Serum Testosterone \>= 300 ng/dL
* Thyroid stimulating hormone (TSH) within institutional normal
* White blood cell count (WBC) \>= 0.5 × institutional lower limit of normal
* The effects of apalutamide 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 90 days 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 90 days after receiving the last dose of study intervention
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* 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 who are taking the following medications that increase seizure risks: (e.g., clozapine, olanzapine, risperidone, ziprasidone), phenothiazine, antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine), bupropion, lithium, meperidine, pethidine, phenothiazine and tricyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline), mirtazapine, selective serotonin reuptake inhibitors (e.g., escitalopram, citalopram, fluoxetine), serotonin norepinephrine reuptake inhibitors (e.g., venlafaxine, desvenlafaxine, levomilnacipran), stimulants (e.g., amphetamines, methylphenidate), monoamine oxidase inhibitors (e.g., phenelzine, selegiline)
* Participants taking any form of anticoagulation (e.g., heparin, warfarin, lovenox, apixaban, rivaroxaban, dabigatran, edoxaban, betrixaban)
* Concurrent use of drugs in category X drug interactions with apalutamide
* Participants receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide
* History of prior or concurrent muscle invading UC, or concurrent prostatic urethral, urethral, or upper tract UC or non-urothelial bladder cancer
* 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 (eg compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
* History of seizures or central nervous system (CNS) metastasis or any condition that in the opinion of the investigator may predispose to seizure or treatment with drugs known to lower the seizure threshold within 4 weeks prior to enrollment in the study
* Participants with severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, long QT, arterial or venous thromboembolic events (eg pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias
* In the opinion of the investigator, participant has uncontrolled hypertension, high cholesterol, or diabetes
* Allergy or hypersensitivity to apalutamide, or excipients, unable or unwilling to take antiandrogen therapy (ADT)
* Plans to father a child while enrolled in this study or within 12 weeks after the last dose of study intervention