Apalutamide and Gonadotropin-Releasing Hormone Analog With or Without Abiraterone Acetate in Treating Participants With Prostate Cancer

This phase II trial studies how well apalutamide and gonadotropin-releasing hormone analog with or without abiraterone acetate work in treating participants with prostate cancer prior to surgery. Apalutamide and abiraterone acetate may stop the growth of cancer cells either by killing the cells or by blocking some of the enzymes needed for cell growth. Hormone therapy, using gonadotropin-releasing hormone analog, may fight prostate cancer by lowering the amount of testosterone the body makes. Giving apalutamide, gonadotropin-releasing hormone analog, and abiraterone acetate may work better in treating participants with prostate cancer.

PRIMARY OBJECTIVES: I. To assess the rate of pathologic stage =\< pT2N0 at prostatectomy for Group A (gonadotropin-releasing hormone analog \[luteinizing hormone releasing hormone agonist (LHRHa)\] plus apalutamide 240 mg orally \[PO\] daily for 6 months as preoperative therapy) and Group B (LHRHa plus apalutamide 240 mg PO daily plus abiraterone acetate 1000 mg PO daily and prednisone 5 mg PO once daily \[QD\] for 6 months as preoperative therapy). SECONDARY OBJECTIVES: I. To assess the tumor epithelium volume following treatment in groups A and B. II. To assess the rate of positive surgical margins in Group A and Group B. III. To assess the time to prostate specific antigen (PSA) recurrence (TTRPSA). IV. To assess the safety profile of the two treatment arms (apalutamide with and without abiraterone acetate and low dose prednisone) for six months in a preoperative setting. EXPLORATORY OBJECTIVES: I. Assessment of the steroid hormone metabolome in blood plasma and tissue by liquid chromatography tandem mass spectrometry. II. Assessment of androgen signaling (canonical and non-canonical) and candidate pathways of resistance to androgen signaling inhibition by protein and ribonucleic acid (RNA) analysis. III. Assessment of citrate intracellular tricarboxylic acid cycle (TCA) metabolite concentrations with liquid chromatography-tandem mass spectrometry (LCMS/MS). IV. Proportion of patients who achieve pathological complete response (CR). V. Hyperpolarized 1-13C-pyruvate imaging at study entry and at 3 months in Arm A and Arm B. OUTLINE: Participants are randomized to 1 of 2 arms. ARM A: Participants receive gonadotropin-releasing hormone analog (leuprolide, goserelin, or triptorelin as determined by treating physician) intramuscularly (IM) once every 3 months and apalutamide PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy. ARM B: Participants receive gonadotropin-releasing hormone analog and apalutamide as in arm A, abiraterone acetate PO QD, and prednisone PO QD. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning no less than 48 hours after completion of therapy, participants undergo radical prostatectomy. After completion of study treatment, participants are followed for 4 weeks.