A Study of an Intermittent ADT Approach With Apalutamide Monotherapy in Participants With mCSPC

The purpose of the study is to determine if the intermittent use of androgen-deprivation therapy (ADT) in participants with metastatic castrate-sensitive prostate cancer (mCSPC) who reached a prostate-specific antigen (PSA) level \< 0.2 nanograms/millilitres (ng/mL) after 6 months of treatment with apalutamide and ADT combination therapy provides non-inferior radiographic progression-free survival (rPFS) and a reduced burden of hot flashes measured as 18-month percent change in severity adjusted hot flash score.

Inclusion Criteria: * Diagnosis of prostate cancer prior to screening with histologically or cytologically confirmed adenocarcinoma of the prostate * For participants not undergoing Gender-affirming care: Metastatic prostate cancer disease documented by conventional imaging (example, computed tomography \[CT\], magnetic resonance imaging \[MRI\], or bone scan) and/or next-generation imaging \[NGI\] demonstrating greater than or equal (\>=) 2 distinct extraprostatic sites of metastasis * For participants undergoing Gender-affirming care: No evidence of metastasis by either conventional imaging (example, CT, MRI, or bone scan) and/or NGI is also acceptable * For participants not undergoing gender-affirming care: testosterone levels \> 50 (ng/dL) nanograms per deciliter at screening, except for those who may have received ADT prior to screening. Participants are allowed to have received up to 3 months of (ADT) androgen-deprivation therapy prior to enrollment * For participants undergoing Gender-affirming care: There is no testosterone level requirement for inclusion * Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Participants with ECOG PS 2 or 3 are eligible for the study if the ECOG PS score is related to stable physical limitations (example, wheelchair-bound due to prior spinal cord injury) and not related to prostate cancer or associated therapy * A participant must agree not to plan to conceive a child while enrolled in this study or within 3 months after the last dose of study treatment * Must be able to take whole apalutamide tablets by swallowing alone or with another vehicle (example, applesauce) * Assigned male at birth, inclusive of all gender identities Exclusion Criteria: * History of seizure or known condition that has been determined to significantly predispose to seizure per investigator * Pelvic lymph nodes as only site of metastasis * Known allergies, hypersensitivity, or intolerance to excipients of apalutamide * Any of the following within 6 months prior to screening: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant arterial or venous thromboembolic events * Gastrointestinal disorder affecting absorption * Participants who have undergone a bilateral orchiectomy with the exception of participants who completed this as part of their gender-affirming care or a result of a variation in physical sex development