This phase III trial compares the effect of adding docetaxel to hormonal therapy and apalutamide versus hormonal therapy and apalutamide alone in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Hormone therapy for prostate cancer, also called androgen deprivation therapy (ADT), uses surgery or drugs to lower the levels of male sex hormones in a man's body. This helps slow the growth of prostate cancer. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Giving docetaxel in addition to the usual treatment of hormonal therapy and apalutamide may work better in treating patients with metastatic prostate cancer than the usual treatment alone.

This study is being done to answer the following question: Is the strategy to give higher doses of radiotherapy treatment over a shorter period of time using special equipment and fewer treatments (also known as Stereotactic Body Radiation Therapy or SBRT) as effective as usual external radiation therapy given with a brachytherapy boost (which involves radiation sources inserted directly into the prostate)?

This phase III trial compares the addition of apalutamide, with or without targeted radiation therapy, to standard of care treatment versus standard of care treatment alone in patients with prostate cancer biochemical recurrence (a rise in the blood level of prostate-specific antigen [PSA] after treatment with surgery or radiation). Diagnostic procedures, such as positron emission tomography/computed tomography (PET/CT), may help doctors look for cancer that has spread to the pelvis. Androgens can cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET/CT results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.

This phase III trial studies whether adding apalutamide, abiraterone acetate, and prednisone to the usual treatment improves outcome in patients with lymph node positive prostate cancer after surgery. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgens, or male sex hormones, can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may help stop or reduce the growth of prostate cancer cell growth by blocking the attachment of androgen to its receptors on cancer cells, a mechanism similar to stopping the entrance of a key into its lock. Abiraterone acetate blocks some of the enzymes needed for androgen production and may cause the death of prostate cancer cells dependent on androgen for their growth. Prednisone may help abiraterone acetate work better by making tumor cells more sensitive to the drug. Adding apalutamide and abiraterone acetate with prednisone to the usual hormone therapy and radiation therapy after surgery may stabilize prostate cancer and prevent it from spreading and extend time without disease spreading compared to the usual approach.

This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading.

This phase II trial tests whether relugolix and radiation therapy works to shrink tumors in patients with prostate cancer that has spread in a limited way to 1 to 5 other parts of the body (oligometastatic). Testosterone can cause the growth of prostate cancer cells. Relugolix lowers the amount of testosterone made by the body. This may help stop the growth of tumor cells that need testosterone to grow. Giving relugolix with radiation therapy may help lower the chance of prostate cancer growing or spreading.

This phase III trial compares stereotactic body radiation therapy (SBRT), (five treatments over two weeks using a higher dose per treatment) to usual radiation therapy (20 to 45 treatments over 4 to 9 weeks) for the treatment of high-risk prostate cancer. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period of time. This trial is evaluating if shorter duration radiation prevents cancer from coming back as well as the usual radiation treatment.

This phase III trial studies whether the addition of definitive treatment (radiation or surgical removal) of the primary tumor to standard systemic therapy for patients with prostate cancer, may help prevent the cancer from the spreading to other parts of their body. Removing the prostate by either surgery or radiation therapy in addition to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.

This phase III trial compares the effect of adding carboplatin to the standard of care chemotherapy drug cabazitaxel vs cabazitaxel alone in treating prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels (castrate-resistant) and that has spread from where it first started (primary site) to other places in the body (metastatic). Giving carboplatin with the standard of care chemotherapy drug cabazitaxel may be better at treating metastatic castrate-resistant prostate cancer.