Stage III Prostate Cancer AJCC v8

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 II trial studies the effect of androgen ablation therapy with or without niraparib after standard of care radiation therapy in treating patients with prostate cancer that has not spread to other parts of the body (localized) or that has spread to nearby tissue or lymph nodes (locally advanced). Androgen ablation therapy (also known as hormone therapy) lowers the levels of male hormones called androgens in the body. Androgens stimulate prostate cancer cells to grow. There are 2 types of androgen ablation therapy given in this study: AAP + ADT and Apa + ADT. AAP + ADT is the treatment combination of the drugs abiraterone acetate and prednisone (AAP) given with androgen deprivation therapy (ADT, also known as androgen deprivation therapy or androgen suppression medication, which is used as standard of care to lower testosterone levels in men with high risk localized or metastatic prostate cancer). Apa + ADT is the treatment combination of the drug apalutamide (Apa) given with ADT. Androgen ablation therapy with or without niraparib after radiation therapy may help to control the disease in patients with prostate cancer.

This phase II trial studies if talazoparib works in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and has mutation(s) in deoxyribonucleic acid (DNA) damage response genes who have or have not already been treated with another PARP inhibitor. Talazoparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. All patients who take part on this study must have a gene aberration that changes how their tumors are able to repair DNA. This trial may help scientists learn whether some patients might benefit from taking different PARP inhibitors "one after the other" and learn how talazoparib works in treating patients with advanced cancer who have aberration in DNA repair genes.

This clinical trial evaluates a golf recreational exercise program for enhancing survivorship in underrepresented prostate cancer survivors. Golf is a multimodal recreational activity that requires participants to utilize all muscle groups to perform the golf swing, walk over hilly and uneven terrain, maintain balance during putting and squat-like tasks. Physical activity and exercise are beneficial to physical function, cognitive function, psychosocial health, and overall quality of life during prostate cancer survivorship. These aspects of health are impacted by prostate cancer treatment, especially androgen deprivation therapy. Additionally, supervised, group-based activity programs facilitate participation in physical activity. Researchers want to examine the changes in functional abilities, psychosocial health, and quality of life following participation in in a golf program designed for prostate cancer survivors.

This phase IV trial studies the effects of testosterone replacement therapy (TRT) on treatment outcomes in hypogonadal men with prostate cancer that has not spread to other parts of the body (localized) and who are on active surveillance (AS). AS in prostate cancer involves closely watching the patient's condition through regular physical exams and blood tests, but not giving treatment unless there are changes in test results. It can be a practical alternative to treatment in localized prostate cancer. Hypogonadal men have low testosterone associated with symptoms such as low libido and erectile problems. TRT can be used to treat hypogonadism by increasing testosterone levels, which may improve associated symptoms. TRT is often not used in men with prostate cancer due to concerns it may lead to the cancer growing or spreading. This may lead hypogonadal men to have a poor quality of life or to discontinue AS. TRT may improve treatment and quality of life outcomes in hypogonadal men with localized prostate cancer on active surveillance.

This clinical trial evaluates whether having a trained peer navigator helps African American men with prostate cancer that has spread to other parts of the body (metastatic) understand and navigate the genetic testing process better than not having a peer navigator. Genetic testing for men with prostate cancer is very important for making treatment and management decisions. However, understanding the risks, benefits, and steps of genetic counseling and testing can be very challenging for patients. African American men are especially less likely to participant in genetic testing due to lack of awareness or understanding, cultural beliefs, finances, or mistrust of the healthcare system. A peer navigator, someone who helps a patient through the information and the process, may be helpful to some men. This study evaluates whether having a peer navigator throughout the genetic evaluation process helps patients understand and engage in the process more.

This clinical trial evaluates the use of an imaging scan (18F-rhPSMA-7.3 positron emission tomography \[PET\]/magnetic resonance imaging \[MRI\]) for identifying patients who are at risk of having their disease spread to the lymph nodes in those undergoing radical prostatectomy for prostate cancer that has not spread to other parts of the body (localized). Prostate specific membrane antigen (PSMA) PET/computed tomography (CT) has emerged as an option to stage newly diagnosed high risk prostate cancer patients. PSMA PET/CT has demonstrated improved diagnostic accuracy for identifying metastasis. PET is procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is used. Because cancer cells often use more glucose than normal cells, the pictures can be used to find cancer cells in the body. MRI is procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. This study may help researchers learn whether 18F-rhPSMA-7.3 PET/ MRI may improve predicting which patients are at risk of lymph node metastases and who are suitable candidates for pelvic lymph node dissection in patients with localized high-risk prostate cancer undergoing radical prostatectomy.

This clinical trial evaluates changes in quality of life after two treatments with near margin-less adaptive radiation therapy (ART) compared to five treatments with standard stereotactic ablative body radiotherapy (SABR) in patients with prostate cancer that has not spread to other parts of the body (localized). ART is a type of radiation therapy that uses information gathered during the treatment cycle to inform, guide, and alter future radiation treatments with respect to location and dose. It may be able to deliver radiation to the site of disease over a shorter time and with smaller margins (less treatment delivered to nearby healthy tissues). SABR is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Shorter duration near margin-less ART may be just as effective at treating patients with localized prostate cancer but have less quality of life side effects than standard SABR.

This phase II trial evaluates the impact of cancer therapy in the patients' home compared to in the clinic on safety, side effects, patient preference, and satisfaction in Black men with prostate cancer that has spread to nearby tissue or lymph nodes (locally advanced), that has increasing prostate-specific antigen after treatment (biochemically recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Typically drug-related cancer care is conducted at a medical center which causes patients to have to spend considerable time away from family, friends, and familiar surroundings. This separation may add to the physical, emotional, social, and financial burden for patients and their families during this difficult time in their lives. Therapy administered to a patient in the patients' residence in the comfort of familiar surrounding using Cancer Connected Access and Remote Expertise (CARE) Beyond Walls (CCBW) may help reduce psychological and financial distress, increase access to care and improve treatment compliance. Giving cancer therapy in the home compared in the clinic may be safe, tolerable and improve patient satisfaction with overall cancer care in Black men with locally advanced, biochemically recurrent or metastatic prostate cancer.

This phase II trial studies how well a short course of androgen deprivation therapy (ADT) with relugolix works in increasing expression of prostate-specific membrane antigen (PSMA) and improving diagnostic imaging with PSMA positron emission tomography (PET)/computed tomography (CT) in patients with high risk or very high risk prostate cancer. PSMA PET/CT has become the standard of care in imaging for high-risk prostate cancer. However, a limitation of PSMA PET/CT is its ability to detect cancer that has spread to the lymph nodes. PSMA is a protein that is usually found on the surface of normal prostate cells but is found in higher amounts on prostate tumor cells. Studies have shown that expression of PSMA is regulated by androgens (male reproductive hormones). Relugolix binds to gonadotropin-releasing hormone receptors in the pituitary gland, which blocks the pituitary gland from making the hormones follicle-stimulating hormone and luteinizing hormone. This causes the testicles to stop making testosterone. Relugolix may stop the growth of tumor cells that need testosterone to grow. PSMA PET/CT is an imaging procedure that is used to help find prostate tumor cells in the body. For this procedure, a cell-targeting molecule linked to a radioactive substance (flotufolastat F 18 in this trial) is injected into the body and travels through the blood. It attaches to PSMA that is found on the surface of prostate tumor cells. PET/CT scanners detect high concentrations of the radioactive molecule and shows where the prostate tumor cells are in the body. Giving a short course of ADT with relugolix may increase PSMA expression to detect smaller areas of prostate cancer that were not previously detected.

This phase II trial compares the effects, good and/or bad of abiraterone and prednisone or darolutamide alone in treating patients with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Androgens (male hormones) can cause the growth of prostate tumor cells. Abiraterone acetate lowers the amount of androgens made by the body. This may help stop the growth of prostate tumor cells that need androgen to grow. Darolutamide blocks the use of androgens by the tumor cells. Prednisone is used to lessen inflammation and lower the body's immune response. Researchers want to compare the side effects of standard of care (SOC) abiraterone and prednisone or darolutamide alone in treating patients with advanced prostate cancer.

This phase III/IV trial compares the impact of leuprolide and abiraterone acetate (AA) versus relugolix and AA on the heart in hormone-naive patients with advanced prostate cancer receiving pelvic radiation therapy. Leuprolide is in a class of medications called gonadotropin-releasing hormone agonists (GNRHa). It prevents the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate tumor cells that need testosterone to grow. Abiraterone acetate, an androgen biosynthesis inhibitor, works by decreasing the amount of certain hormones in the body. Relugolix, a GNRH antagonist, works by decreasing the amount of testosterone produced by the body. This may slow or stop the spread of prostate tumor cells that need testosterone to grow. The use of hormone therapy with radiation therapy has been shown to improve survival, however, studies have suggested that the addition of hormone therapy may worsen heart (cardiac) disease and high blood pressure. In fact, studies have shown that the most common cause of death in prostate cancer patients is due to heart disease or heart attacks. Computed tomography (CT) scans create a series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an x-ray machine. In this study, sophisticated cardiac CT images are used to take pictures of patients' heart and coronary arteries to help assess damage to the heart. Using cardiac CT and blood tests, this trial may help doctors determine which patients are at risk of cardiac disease when treated with combination hormone therapy, as well as the differential risk of leuprolide versus relugolix in combination with abiraterone acetate.

This phase II trial investigates whether proton radiation therapy directed to the prostate tumor, pelvic, and para-aortic lymph nodes, is an effective way to treat patients with high-risk or lymph node positive prostate cancer who are receiving radiation therapy, and if it will result in fewer gastrointestinal and genitourinary side effects. Proton beam therapy is a new type of radiotherapy that directs multiple beams of protons (positively charged subatomic particles) at the tumor target, where they deposit the bulk of their energy with essentially no residual radiation beyond the tumor. By reducing the exposure of the healthy tissues and organs to radiation in the treatment of prostate cancer, proton therapy has the potential to better spare healthy tissue and reduce the side effects of radiation therapy.

This clinical trial studies the side effects of image-guidance and online adaptation with stereotactic body radiation therapy (SBRT) for the treatment of patients with prostate adenocarcinoma that has not spread to other parts of the body (localized). Image-guided SBRT is a standard treatment for localized prostate cancer. This treatment uses imaging of the cancer within the body to define and localize the area to be treated with the radiation. Imaging can be obtained using either computed tomography (CT), magnetic resonance imaging (MRI), or a combination of the two. Typically, with SBRT, a radiation plan is developed based on the CT or MRI images obtained before treatment begins and adjustments are not made to the plan during treatment. However, anatomy can be different from day-to-day which may cause radiation to be delivered to the normal surrounding structures and possibly more side effects. During image-guided SBRT with online adaptation, the initial radiation plan is designed similarly; however, when the patient presents for radiation, the attending radiation oncologist, a dosimetrist, and a medical physicist "re-optimize" the radiation plan using the current anatomy of the day, meaning the changes in bladder and prostate size/shape are taken into account. The initial plan and the re-optimized plan are then compared, and the plan that has the optimal balance between delivering a tumor killing dose of radiation and minimizing radiation dose to normal surrounding structures is delivered. Image-guidance and online adaptation with SBRT may lower side effects and be a safer way to treat localized prostate adenocarcinoma.

This phase III trial tests the side effects of stereotactic body radiation therapy (SBRT) compared to hypofractionated radiotherapy for treating patients with prostate adenocarcinoma that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to a limited number of sites (oligometastatic). SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumors cells and have fewer side effects. SBRT may work just as well as hypofractionated radiation therapy at treating patients with biochemically recurrent or oligometastatic prostate cancer, but with a shorter treatment time and possibly fewer side effects.

This phase III trial tests whether high-dose vitamin D works in treating androgen-deprivation therapy (ADT)-induced bone loss in patients with prostate cancer who are undergoing androgen-deprivation therapy. Vitamins are substances that the body needs to grow and develop normally. Vitamin D helps the body absorb calcium. Calcium is one of the main building blocks of bone. A lack of vitamin D can lead to bone diseases such as osteoporosis or rickets. This trial may help researchers determine if high-dose vitamin D helps keep bones strong, lowers number of falls, and lessens fatigue in men getting androgen-deprivation therapy.

This clinical trial studies whether a new multi-layer perinatal tissue allograft, MLG-Complete (Trademark), can be used to improve complications after nerve-sparing robot-assisted radical prostatectomy (RARP) in patients with prostate cancer that has not spread to other parts of the body (localized). Two major complications that can happen after complete surgical removal of the prostate (radical prostatectomy) include erectile dysfunction and urinary incontinence, both of which greatly affect a patient's quality of life and social well-being. The goal of nerve-sparing radical prostatectomy is to preserve erectile and urinary function, but damage to the surrounding nerves and blood vessels can still occur causing the patient to experience the complications. An allograft is the transplant of an organ, tissue, or cells from one individual to another individual of the same species who is not an identical twin. The MLG-Complete allograft is made up of perinatal tissue and is placed on the nerve bundles during a nerve-sparing RARP. It is meant to serve as a barrier and provide coverage to the nerve bundles from the surrounding environment, which may improve post-nerve-sparing RARP complications.

This clinical trial studies the side effects of computed tomography (CT)-guided stereotactic body radiation therapy (SBRT) with intrafraction motion monitoring and to see how well it works in treating patients with prostate cancer that has not spread to other parts of the body (localized). In CT-guided SBRT, x-ray-based imaging and cone-beam CTs are used to define and localize the area to be treated with SBRT. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. A recent randomized trial showed that while SBRT is associated with less urinary incontinence and erectile dysfunction than complete surgical removal of the prostate, there are more urinary irritative side effects and more bowel side effects than with surgery. One source of uncertainty in SBRT that may contribute to genitourinary (GU) and gastrointestinal (GI) side effects is the necessity of treating a "margin" of volume around the prostate to account for its movement during SBRT. Intrafraction motion monitoring is any technique or system designed to track the movement of the body and target during fractions of external beam radiation to keep the beam on target. This allows for the patient to be repositioned, if needed, to ensure delivery of the SBRT to only the planned treatment area. CT-guided SBRT with intrafraction motion monitoring may lower GU and GI side effects by allowing tighter margins, as has been demonstrated with magnetic resonance imaging (MRI)-guided SBRT.

This phase II trial tests how well bright white light (BWL) therapy works in reducing cancer-related fatigue and depression in patients with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and who are undergoing treatment with antiandrogen therapy (ADT) combination therapy. Combination treatment including ADT plus chemotherapy and androgen receptor (AR) targeted therapy or ADT plus AR targeted therapies work by reducing testosterone. Most prostate tumor cells rely on testosterone to help them grow; therefore, ADT combination therapy causes prostate tumor cells to die or to grow more slowly leading to improved overall survival in men with advanced prostate cancer when compared with ADT alone. However, lower levels of testosterone is also commonly associated with worsening fatigue and depression. If prolonged and severe, these complications can alter patient treatment plans, impacting not just quality of life, but leading to inadequate cancer control. BWL therapy is a type of phototherapy that utilizes bright white full-spectrum light, either through a light box or light therapy glasses to help regulate circadian rhythms. Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle, including the sleep-wake cycle which can become disrupted in cancer patients undergoing treatment, leading to increased fatigue. Additionally, exposure to bright light may increase the production of serotonin, a neurotransmitter that is associated with mood regulation. BWL therapy with AYOpro light therapy glasses may serve as a supportive care measure for men with advanced prostate to help reduce fatigue, as well as improve mood and overall quality of life during ADT combination therapy to maintain cancer care without suffering complications of therapy.

This phase II trial investigates the effect of high dose-rate brachytherapy and stereotactic body radiotherapy in treating patients with prostate adenocarcinoma. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Stereotactic body radiation therapy 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 and cause less damage to normal tissue.

This phase II trial evaluates the best duration for relugolix to be given in combination with radiation therapy when treating patients with high risk prostate cancer. Prostate cancer is a hormonal influenced cancer. Part of the usual treatment for patients with prostate cancer is androgen deprivation therapy (ADT). ADT is used to lower the amount of testosterone in the body, because testosterone appears to help prostate cancer grow. Relugolix works to reduce testosterone levels, which may inhibit proliferation of prostate cancer cells. It is approved by the Food and Drug Administration to treat prostate cancer. Adding relugolix to standard radiation therapy might work better and have fewer side effects than prior forms of hormonal therapy, but the optimal duration of relugolix in combination with radiation is not known.