Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology.
• Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening.
• Evidence of disease progression from either, >4 weeks from last flutamide treatment, or >6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy.
• Current evidence of metastatic disease.
• Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment.
• Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for >4 weeks before randomization.
• Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
• Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load.
• Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:
• History of pituitary dysfunction.
• Poorly controlled diabetes mellitus.
• Active or unstable cardio/cerebro-vascular disease, including thromboembolic events and history of stroke or transient ischemic attack within 6 months before the first dose of study intervention, history of myocardial infarction within 6 months before the first dose of study intervention, New York Heart Association Class III or IV cardiac disease or congestive heart failure, coronary heart disease that is symptomatic, or unstable angina
• History or family history of long corrected QT interval (QTc) syndrome.
• Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML.
• History or current condition of adrenal insufficiency.
• History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications.
• Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention.
• Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization).
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities, requiring corticosteroids.
• Received a live or live-attenuated vaccine within 30 days before the first does of study intervention. Administration of killed vaccines is allowed.
• Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Active autoimmune disease that has required systemic treatment in the past 2 years.
• Active infection requiring systemic therapy.
• Concurrent active HBV or HCV infections.

Inclusion Criteria:

• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patients must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with malignant germ cell tumor (stage II or higher).
• Histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment , with the following exceptions:
• Among patients were initially diagnosed with completely resected non-seminoma malignant GCT and later recur during observation post surgery, a diagnostic biopsy is not required for enrollment if elevated tumor markers rise to > 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart. The pathology report of initial surgery should be provided
• Patients may be enrolled without histologic or cytologic confirmation in the rare case where there are exceptionally raised tumor markers (alpha fetoprotein [AFP- ≥ 500 ng/mL or HCG ≥ 500 IU/L) and radiologic features consistent with GCT. In addition, the treating clinician must deem that the patient's tumor is not suitable for upfront resection and that a biopsy is not in the patient's best interest; or that there is a need to start therapy urgently
• Low risk immature teratoma (IT); site: ovarian; stage: any; grade: any; histology: pure immature teratoma, mixed immature and mature teratoma, (may contain microscopic foci of yolk sac tumor [< 3 mm], but no other pathological evidence of MGCT); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain only seminoma; may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC-IV, (International Germ Cell Consensus Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) < 11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II, III, and III-X, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma: must be IGCCC good risk; post op: alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 3.0 x normal; age (years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Pure seminoma patients are not eligible for the standard risk arms of the study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
• A serum creatinine based on age/sex as follows (within 7 days prior to enrollment): (mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 2 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, malignant involvement of liver or vanishing bile duct syndrome
• Peripheral absolute neutrophil count (ANC) >= 750/mm^3 (within 7 days prior to enrollment) AND
• Platelet count >= 75,000/mm^3 (within 7 days prior to enrollment)
• Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University

Exclusion Criteria:

• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
• Pure ovarian or extragonadal dysgerminoma/seminoma
• Pure mature teratoma
• Pure immature teratoma with alpha-fetoprotein (AFP) >= 1000 ng/mL
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage II- IV extragonadal, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain [stage IV disease] would be considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:
• Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening
• Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography (CT)/magnetic resonance imaging (MRI)
• Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) (metastatic hormone-sensitive prostate cancer [mHSPC] or non-metastatic hormone-sensitive prostate cancer [nmHSPC]), or castration-resistant prostate cancer (CRPC) (metastatic castration-resistant prostate cancer [mCRPC] or non-metastatic castration-resistant prostate cancer [nmCRPC]), for at least 8 weeks of NHA treatment (at least 14 weeks of NHA treatment for participants with bone progression). Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel
• Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
• Has ongoing androgen deprivation therapy (ADT) with serum testosterone <50 ng/dL (<1.7 nM)
• Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 10 days before randomization
• Has adequate organ function
• Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Participants who have adverse event (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy (HRT) or participants who have ≤Grade 2 neuropathy or ≤Grade 2 osteopenia/osteoporosis are eligible
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:
• Has presence of gastrointestinal condition
• Is unable to swallow capsules/tablets
• Has history of pituitary dysfunction
• Has poorly controlled diabetes mellitus
• Has clinically significant abnormal serum potassium or sodium level
• Has any of the following at screening visit: Hypotension: systolic blood pressure (BP) <110 mmHg, or uncontrolled hypertension: systolic BP ≥160mmHg or diastolic blood BP ≥90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive therapy
• Has a history of active or unstable cardio/cerebrovascular disease, including thromboembolic events
• History or family history of long QTc syndrome
• Has a history of seizure(s) within 6 months before providing documented informed consent (IC) or has any condition that may predispose to seizure within 12 months prior to the date of enrollment
• Has a history of clinically significant ventricular arrhythmias or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place
• Has received a taxane-based chemotherapy for metastatic castration-resistant prostate cancer (mCRPC)
• Has not adequately recovered from major surgery or have ongoing surgical complications
• Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures
• Participants on an unstable dose of thyroid hormone therapy, as judged by the investigator, within 6 months before the start of the study intervention
• Receives prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids
• Receives prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
• Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein (P-gp) inhibitors within 2 weeks before the first dose of study intervention
• Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or opevesostat
• Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention
• Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is allowed
• Active infection requiring systemic therapy
• Has concurrent active Hepatitis B virus and Hepatitis C virus infection

Inclusion Criteria:

1. ≥18 years of age (or the local legal age of consent). 2. Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone, soft tissue, or extra-pelvic nodal region each < 5 cm or < 250 cm3 that develop within the past 6-months that are seen on imaging. A nodal lesion is defined to include nodal conglomerates located in the same nodal chain such that they can be treated in one SABR field. Up to five lesions are allowed on advanced functional imaging such as fluciclovine (Axumin), choline or Prostate Specific Membrane Antigen (PSMA) PET-CT scan. 1. CT or MRI scan within 6 months of enrollment 2. Bone scan within 6 months of enrollment 3. Fluciclovine (Axumin), choline, or PSMA PET-CT scan within 6 months of enrollment (PET-CT scan is reasonable for study entry imaging as an alternative to CT/MRI scan and bone scan) 3. Must have a high-risk pathogenic mutation (TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH) by next generation sequencing. ATM mutation enrollment will be capped at 5% of the overall population. 4. Histologic confirmation of prostate adenocarcinoma (primary or metastatic tumor). 5. Patient may have had prior systemic therapy and/or ADT so long as testosterone is > 100 ng/dl prior to enrollment 6. PSA > 0.5 but <50 at enrollment. 7. Prostate Specific Antigen Doubling Time (PSADT) < 15 months 8. Baseline testosterone > 100 ng/dl 9. Patient must have a life expectancy ≥ 12 months. 10. Patient must have an ECOG performance status ≤ 2. 11. Adequate hematologic, renal, and hepatic function at screening defined as follows: • Absolute neutrophil count ≥1.5 x 109/L • Hemoglobin ≥9.0 g/dL, independent of transfusions for at least 28 days
• Platelet count ≥100 x 109/L
• Creatinine <2 x upper limit of normal (ULN)
• Serum potassium ≥3.5 mmol/L
• Serum total bilirubin ≤1.5× ULN or direct bilirubin ≤1 x ULN (Note: In participants with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 × ULN, participant may be eligible)
• AST or ALT ≤3 × ULN 12. Patient must have the ability to understand and the willingness to sign a written informed consent document 13. Able to swallow the study medication tablets whole. 14. While on study medication and for 4 months following the last dose of study medication, a male participant must agree to use condom and an adequate contraception method for female partner (WOCBP) A male participant must agree not to donate sperm while on study treatment and for a minimum of 4 months following the last dose of study medication. 1. Castration-resistant prostate cancer (CRPC). 2. Prior radiation therapy to an overlapping site of a target lesion that would preclude further radiation therapy 3. Spinal cord compression or impending spinal cord compression. 4. Suspected intracranial and/or liver metastases (>10 mm in largest axis). 5. Patient receiving any other investigational agents. 6. Inability to receive any form of systemic therapy in the opinion of a treating medical oncologist. 7. Unable to lie flat during or tolerate PET/MRI, PET/CT or SABR. 8. Radiographical evidence of cranial parenchymal metastasis. 9. Active second primary malignancy; AML/MDS in medical history. 10. Uncontrolled hypertension and myocardial infarction/PE/cardiac failure in last 6 months. 11. Prior treatment with PARP inhibitor 12. Refusal to sign informed consent. 13. Pathological finding consistent with small cell or neuroendocrine carcinoma of the prostate. 14. History of adrenal dysfunction 15. Long-term use of systemically administered corticosteroids (>5mg of prednisone or the equivalent) during the study is not allowed. Short-term use (≤4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated. 16. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
• non-muscle invasive bladder cancer.
• skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
• malignancy that is considered cured with minimal risk of recurrence.
• History or current diagnosis of MDS/AML. 17. Current evidence within 6 months prior to randomization of any of the following: • severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, • clinically significant arterial or venous thromboembolic events (ie. Pulmonary embolism), or clinically significant ventricular arrhythmias. 18. Presence of sustained uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive treatment. 19. Known allergies, hypersensitivity, or intolerance to the excipients of niraparib/abiraterone acetate tablets 20. Current evidence of any medical condition that would make prednisone use contraindicated. 21. Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study medication. 22. Participants who have had the following ≤28 days prior to randomization: • A transfusion (platelets or red blood cells); • Hematopoietic growth factors; • Major surgery 23. Human immunodeficiency virus positive participants with 1 or more of the following: • Not receiving highly active antiretroviral therapy or on antiretroviral therapy for less than 4 weeks.
• Receiving antiretroviral therapy that may interfere with the study medication
• CD4 count <350 at screening.
• An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
• Human immunodeficiency virus load >400 copies/mL 24. Active or symptomatic viral hepatitis or chronic liver disease; encephalopathy, ascites or bleeding disorders secondary to hepatic dysfunction. 25. Moderate or severe hepatic impairment (Class B and C per Child-Pugh classification system.

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 270 days prior to registration
• Unfavorable intermediate risk prostate cancer, defined as having ALL the following bulleted criteria:
• Has at least one intermediate risk factor (IRF):
• PSA 10-20 ng/mL
• Clinical stage T2b-c (digital rectal examination [DRE] and/or imaging) by American Joint Committee on Cancer (AJCC) 8th edition
• Gleason score 7 (Gleason 3+4 or 4+3 [ International Society of Urological Pathology (ISUP) Grade Group 2-3])
• Has ONE or more of the following 'unfavorable' intermediate-risk designators:
• > 1 immature reticulocyte fraction (IRF)
• Gleason 4+3=7 (ISUP Grade Group 3)
• >= 50% of biopsy cores positive
• Biopsies may include 'sextant' sampling of right/left regions of the prostate, often labeled base, mid-gland and apex. All such 'sextant' biopsy cores should be counted. Men may also undergo 'targeted' sampling of prostate lesions (guided by MRI, ultrasound or other approaches). A targeted lesion that is biopsied more than once and demonstrates cancer (regardless of number of targeted cores involved) should count as a single additional positive core sampled and positive. In cases of uncertainty, count the biopsy sampling as sextant core(s)
• Absence of high-risk features
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 120 days prior to registration;
• Negative bone imaging (M0) within 120 days prior to registration; Note: Tc-99m bone scan or sodium fluoride (NaF) positron emission tomography (PET) are allowed. Equivocal bone scan findings are allowed if plain films X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) are negative for metastasis at the concerned site(s). While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for bone imaging, any suspicious findings must be confirmed and correlated with conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine eligibility based on the latter modalities (e.g. M0 based on conventional imaging modalities)
• Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MR), within 120 days prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1.0 cm in short axis and/or if biopsy is negative.Note: While a negative fluciclovine, choline, or prostate specific membrane antigen(PSMA) PET may be counted as acceptable substitute for pelvic imaging, any suspiciousfindings must be confirmed by conventional imaging (CT, MRI or biopsy). If the findingsdo not meet pathological criteria based on the latter modalities (e.g. node =< 10 mm inshort axis, negative biopsy), the patient will still be eligible
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
• Non-castrate testosterone level (> 50 ng/dL) within 120 days prior to registration
• Absolute neutrophil >= 1,000 cells/mm^3 (within 120 days prior to registration)
• Hemoglobin >= 8.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
• Platelet count >= 100,000 cells/mm^3 independent of transfusion and/or growth factors (within 120 days prior to registration)
• Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)
• For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin: 1.5 =< institutional upper limit of normal (ULN) (within 120 days prior to registration) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less than or equal to 1.5 x ULN, subject is eligible)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]): =< 2.5 x institutional ULN (within 120 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial; Note: HIV testing is not required for eligibility for this protocol
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
• For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

• Previous radical surgery (prostatectomy) or any form of curative-intent ablation whether focal or whole-gland (e.g., cryosurgery, high intensity focused ultrasound [HIFU], laser thermal ablation, etc.) for prostate cancer
• Definitive clinical or radiologic evidence of metastatic disease (M1)
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. History of or current diagnosis of hematologic malignancy is not allowed
• Prior radiotherapy to the prostate/pelvis region that would result in overlap of radiation therapy fields
• Previous bilateral orchiectomy
• Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate). ADT started prior to study registration is not allowed
• Prior use of 5-alpha-reductase inhibitors is allowed, however, it must be stopped prior to enrollment on the study with at least a 30 day washout period before baseline study PSA measure and registration
• Active testosterone replacement therapy; any replacement therapy must be stopped at least 30 days prior to registration
• Severe, active co-morbidity defined as follows:
• Current severe or unstable angina;
• New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
• History of any condition that in the opinion of the investigator, would preclude participation in this study
• Inability to swallow oral pills
• High risk features, which includes any of the following:
• Gleason 8-10 [ISUP Grade Group 4-5]
• PSA > 20
• cT3-4 by digital exam OR gross extra-prostatic extension on imaging [indeterminate MRI evidence will not count and the patient will be eligible]

Inclusion Criteria:

• 18-80 years of age
• Self-identify as Black or African American
• At least 6-months post diagnosis with any of the following cancers: breast, ovarian, uterine, prostate, colorectal, pancreatic
• Have not had genetic testing for hereditary cancer
• Have received care at one of the participating sites in the prior five years
• Meet National Comprehensive Cancer Network criteria for germline GT
• Able to read and speak in English
• Capable of providing informed consent
• Have internet access (via smartphone, tablet or computer)
• Comfortable using a computer or mobile phone independently to access information

Exclusion Criteria:

• Do not speak English
• Unable to access the Internet
• Have previously undergone germline genetic testing for hereditary cancer risk or previously had genetic counseling (GC) and declined genetic testing (GT)
• Are unable to provide informed consent

Key Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma 2. Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening, according to 1 of the following: 1. PSA progression as defined by a rising PSA level confirmed with an interval of ≥1 week between each assessment 2. Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria with or without PSA progression 3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression NOTE: Measurable disease per RECIST version 1.1 per local reading at screening is not an eligibility criterion for enrollment 3. Has progressed upon or intolerant to ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least one second-generation anti-androgen therapy (e.g. abiraterone, enzalutamide, apalutamide, or darolutamide)

Key Exclusion Criteria:

1. Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities 2. Has received any previous systemic biologic or immune-modulating therapy (except for Sipuleucel-T) within 5 half-lives of first dose of study therapy, as described in the protocol 3. Has received prior PSMA-targeting therapy. Exception: Prior therapy with approved PSMA-targeted radioligand(s) is permitted 4. Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy 5. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments 6. Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living [ADLs]) or uncontrolled seizures in the year prior to first dose of study therapy 7. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency, as described in the protocol.

NOTE: Other protocol defined Inclusion/Exclusion Criteria apply

Inclusion Criteria:

• Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
• Any T-stage is eligible (American Joint Committee on Cancer [AJCC] 8th edition [ed])
• Appropriate stage for study entry based on fluciclovine F-18 PET scan (FACBC, Axumin) F-18 prostate-specific membrane antigen (PSMA) PET (PyLarify) scan, Gallium-68 PSMA PET scan, flotufolastat F-18 PSMA PET scan (Posluma), or C-11 or F-18 Choline PET within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease. For patients with PSA < 0.20 ng/mL at time of registration, PET scan is recommended but not required
• Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen or nodal disease on imaging at time of recurrence (including external iliacs, internal iliacs, and/or obturator nodes); peri-prostatic and peri-rectal nodes can also be considered regional lymphadenopathy and are allowed
• History/physical examination within 90 days prior to registration
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
• Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA > 0 ng/mL at least 30 days after prostatectomy
• Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =< 180 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =< 180 days and stopped prior to registration)
• Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
• Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
• Serum potassium >= 3.5 mmol/L within 90 days prior to registration
• Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 90 days prior to registration)
• Serum albumin >= 3.0 g/dL (within 90 days prior to registration)
• Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for < 3 years must contact the principal investigator, Ronald Chen, Doctor of Medicine (MD)
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

• Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, [FACBC, Axumin], F-18 PSMA PET [Pylarify], flotufolastat F-18 PSMA PET scan [Posluma], Gallium-68 PSMA PET scan or C-11 choline PET)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Androgen deprivation therapy (ADT) prior to radical prostatectomy
• Prior treatment with androgen receptor signaling inhibitor (including but not exclusive to a growing list of: abiraterone acetate, enzalutamide, apalutamide, darolutamide), unless started =< 180 days and stopped prior to registration, which is allowed
• Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
• History of any of the following:
• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
• Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 12 months prior to registration
• New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification.)
• History of any condition that in the opinion of the investigator, would preclude participation in this study
• Current evidence of any of the following:
• Known gastrointestinal disorder affecting absorption of oral medications
• Active uncontrolled infection
• Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
• Baseline moderate and severe hepatic impairment (Child-Pugh Class B & C)
• Inability to swallow oral pills
• Any current condition that in the opinion of the investigator, would preclude participation in this study
• Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
• Patients with inflammatory bowel disease

Inclusion Criteria:

• Histologically proven adenocarcinoma of the prostate
• Evidence of metastasis by magnetic resonance imaging (MRI)/computed tomography (CT) scan, bone scan, or histologic confirmation
• Clinical stage M1a (distant lymph node positive), M1b (bone metastasis), or M1c (solid organ metastasis.
• If solitary lesion, metastasis confirmed with either biopsy or two independent imaging modalities (i.e. CT and PET [positron emission tomography], bone scan and MRI, modality at the discretion of the treating physician)
• No previous local therapy for prostate cancer (i.e prostate radiation, cryotherapy, etc.)
• Give informed consent
• Prostate deemed resectable by surgeon
• Plans to start or has already started antiandrogen therapy (ADT) no longer than 6 months prior to consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Hemoglobin (HgB) >= 9 g/dL compatible for surgery
• Platelets > 80,000/mcL compatible for surgery
• Aspartate aminotransferase (AST) =< 2x upper limit of normal (ULN) compatible for surgery
• Alanine aminotransferase (ALT) =< 2x upper limit of normal (ULN) compatible for surgery

Exclusion Criteria:

• Refuses to give informed consent
• Deemed to have unresectable disease by surgeon
• Received ADT for more than 6 months prior to consent
• Life expectancy of less than 6 months prior to consent
• Active spinal cord compression
• Deep vein thrombosis (DVT) / pulmonary embolism (PE) in the past 6 months prior to consent
• Previous local therapy for prostate cancer
• Patients who have chemotherapy or radiotherapy for non-prostate cancer related treatment within 3 weeks prior to consent