• Patients with suspected prostate cancer (e.g., abnormal digital rectal exam, elevated and/or rising PSA) as determined by referring physician
• Patients must have had a diagnostic, standard of care mpMRI of the prostate with at least one lesion with a PI-RADS v2.1 score ≥ 4
• In men with PI-RADS v2.1 score 4, PSA should be ≥ 10 ng/mL
• Patients must be scheduled for biopsy or radical prostatectomy
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Patients should not have had any type of curative or palliative therapy for prostate cancer before enrolling in the study
• Patients must be medically stable as judged by the patient's physician
• Patients must be able to lie still for a total of 60 minutes for the PET/CT scans
• Ability to understand and the willingness to sign a written informed consent
• Patients who have had a prior prostatectomy or radiotherapy for prostate cancer cannot participate in the study
• Patients who have had a prior biopsy for prostate cancer cannot participate in the study
• Patients who have been treated for cancers other than skin cancers
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study
• Patients may not weigh more than the maximum weight limit for the PET/CT scanner table (>200 kilograms or 440 pounds)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 68Ga PSMA-11 or other agents used in the study such as gadolinium-based intravenous contrast agent used during the mpMRI

• Age between 45-99 years
• Biopsy proven, low-risk, localized prostate cancer (minimum of 8 cores)
• May have had biopsy within last 12 months ≤4 cores involved with cancer
• Gleason score ≤6 with no Gleason pattern 4
• Clinical stage T1c-T2a/b
• Serum PSA ≤15 ng/ml
• Life expectancy > 5 years
• Any previous prostate cancer treatment (radiotherapy, chemotherapy, hormonal therapy, oral glucocorticoids, GnRH analogues, prostatectomy)
• Concurrent or previous use within 6 months of screening of any 5α-reductase inhibitor
• Use of anabolic steroids or drugs with antiandrogenic properties
• Prostate volume >150 grams
• Patients who are taking antiplatelet, anticoagulant agents or have a history of a bleeding disorder. Patients taking 81 mg of Aspirin will be allowed to enroll with close observation
• History of gastric or duodenal ulcers or untreated hyperacidity syndromes. Patients on stable doses of GERD medication allowed.
• Patients who are currently taking or plan to take Curcumin during the study
• Patients with a history of gallbladder surgery or gallstones will be excluded

• radical prostatectomy for adenocarcinoma of prostate
• pathologically confirmed T1-T3 disease
• no sign of lymph node or metastatic disease
• pT1-pT3pNxMx patients in whom standard NCCN or AUA guidelines would suggest are at low risk for pelvic lymph node or metastatic disease and who would not require confirmatory imaging for metastatic disease. This includes patients with Gleason 6 or 7(T2 disease) and PSA less than 20.
• Eastern Cooperative Oncology Group(ECOG) status 0-2
• adequate renal and liver function
• focally positive surgical margins are permitted
• no plan to receive adjuvant hormone or radiation therapy
• PSA at the time of enrollment must be undetectable
• life expectancy of 3 years
• must not have exceeded 3 months from time of surgery to enrollment into study
• T3b or T4 or node positive disease
• macroscopic residual disease after surgery
• hormone therapy before surgery
• history of gallbladder problems or gallstones, or biliary obstruction
• radiation therapy as primary treatment after surgery
• INR value greater than 1.5
• AST/ALT are equal or greater than 2 times the upper limit of normal
• antiplatelet or anticoagulant agents- patients taking 81mg of Aspirin will be allowed with close observation
• history of gastric or duodenal ulcers or hyperacidity syndromes
• patients who are currently taking or plan to take Curcumin during the study

• Appropriate staging studies identifying patient as American Joint Committee on Cancer (AJCC) 7th edition clinical stage T1 (a, b, or c) or T2 (a, b, or c) adenocarcinoma of the prostate gland. The patient should not have direct evidence of regional or distant metastases after appropriate staging studies. See Appendix I for details on AJCC 7th Edition staging criteria. Histologic confirmation of cancer will be required by biopsy performed within 12 months of registration. T-staging may be assessed by multi-parametric imaging alone if digital rectal examination was deferred.
• The patient's Zubrod performance status must be 0-2 (see Appendix II for definition).
• The Gleason summary score should be less than or equal to 7 [Grade group 1 (Gleason 3+3=6), group 2 (Gleason 3+4=7), and group 3 (Gleason 4+3=7) are allowed]. See Appendix III for details on definitions. While a template biopsy is recommended, it is not required in the case of MRI fusion biopsy performed on all dominant MR lesions (defined as Prostate imaging
•reporting and data system (PIRADS) v2 4-5).
• Baseline AUA symptom score ≤19 (see Appendix IV for questionnaire) without need for maximum medical therapy (specifically, not on tamsulosin 0.8mg daily)
• EPIC sexual domain composite score 60-100 (see Appendix V)
• Multi-parametric MRI evaluation of the prostate is required for this study within 90 days of registration. Gross radiographic disease on MRI (defined as PIRADS v2 score 3-5) must be > 5mm at minimum distance from at least one side's neurovascular bundle, which is typically the closest of the neurovascular elements to the prostate.
• The serum PSA should be less than or equal to 20 ng/ml within 90 days of registration.
• Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT or anti-androgen therapy; (3) within 30 days after discontinuation of finasteride; (4) within 90 days after discontinuation of dutasteride; (5) within 5 days of a digital rectal examination.
• Ultrasound or MRI based volume estimation of prostate gland ≤ 80 grams. Cytoreduction therapy (finasteride or dutasteride only) may be considered for those with >60 gram size.
• All patients must be willing and capable to provide informed consent to participate in the protocol within the 30 days prior to registration
• Subjects with clinical (digital rectal examination) evidence of extraprostatic extension (T3a) or seminal vesicle involvement (T3b). MRI evidence of equivocal/potential but not definite extraprostatic extension is allowed, as long as it is unilateral and not on the side of the gland proposed for neurovascular element sparing. In equivocal cases of potential extracapsular extension on MRI only, discretion is left to the treating physician.
• MRI evidence of gross disease (defined as PIRADS v2 score 3-5 lesions) ≤5mm of BOTH neurovascular bundles, which are the most proximate of the neurovascular elements planned for sparing on this protocol.
• Patients with all three intermediate risk factors (PSA >10 and ≤ 20, Gleason 7, clinical stage T2b-T2c) who ALSO have ≥50% of the number of their template biopsy cores positive for cancer are ineligible.
• Inability to undergo multi-parametric MRI.
• Evidence of metastatic disease. Note bone scan is not required for this study given the low-intermediate NCCN risk cohort to be enrolled.
• Evidence of clinical nodal involvement of the pelvis. Biopsy is required for lymph nodes over ≥1.5cm in short-axis measured size.
• No current ADT or anti-androgen therapy at time of registration is allowed. Further, no more than 3 cumulative months of prior ADT or anti-androgen therapy is allowed. If either has been used by the patient, there must be a demonstration of full testosterone recovery (>280ng/dL serum blood level), EPIC sexual domain score ≥60, and at least 1 month between demonstration of testosterone recovery and study registration (any one measurement of testosterone recovery suffices).
• Testosterone ≤ 280 ng/dL (any one measurement >280 ng/dL suffices for inclusion)
• Subjects who have had previous pelvic radiotherapy or have had chemotherapy or surgery for prostate cancer.
• Subjects who have plans to receive other concomitant or post treatment adjuvant antineoplastic therapy while on this protocol including surgery, cryotherapy, conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy given as part of the treatment of prostate cancer.
• Subjects who have undergone previous transurethral resection of the prostate (TURP) or ablative procedures to the prostate for benign prostatic hyperplasia or other conditions (i.e. cryotherapy, HIFU).
• Subjects who have baseline severe urinary symptoms, as defined by AUA symptom score >19 (alpha-blocker medication allowed except if taking tamsulosin 0.8mg daily at baseline which indicates compensated severe symptoms and also can affect sexual function).
• Subjects who have a history of significant psychiatric illness that would confound informed consent.
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration
• Patients with active inflammatory colitis (including Crohn's Disease and ulcerative colitis) currently requiring systemic steroids and/or systemic immunosuppression are not eligible.
• Subjects with a known allergy to polyethylene glycol hydrogel (rectal spacer material) or contraindication to spacer products (Duraseal or SpaceOAR)
• Subjects with uncontrolled coagulation disorder which cannot be controlled with anticoagulants
• Men of reproductive potential who do not agree that they or their partner will use an effective contraceptive method such as condom/diaphragm and spermicidal foam, intrauterine device (IUD), or prescription birth control pills.
• Men who require erectile function medication or aid to achieve an erection sufficient for intercourse. Ability to achieve erection sufficient for intercourse without medication or aid at least once time in the month prior to registration is sufficient for inclusion.
• Men who have clinically significant penile malformation (i.e. Peyronie's disease) or history of penile implantation are excluded.
• If DRE is performed, patient may not have palpable disease on side of gland to be planned for neurovascular sparing. Given the poor accuracy of DRE, such a finding should be confirmed by MRI and/or biopsy to harbor actual disease before excluding a patient on this basis.

• Pathologically (histologically) proven adenocarcinoma confirmed by prostatectomy performed within 10 years prior to registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted.
• PSA level (≥ 0.7 ng/mL) within 90 days prior to registration. GnRH analog may be started no more than 42 days prior study entry, but patients must have a PSA ≥ 0.7 ng/mL prior to starting ADT.
• Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to registration.
• Platelet count ≥ 75,000 x 109/µL independent of transfusion and/or growth factors within 90 days prior to registration.
• At least 1 of the following aggressive features:
• Gleason score of 8-10 (note any Gleason score is eligible)
• Seminal vesicle invasion (SVI) (note any pT stage [AJCC v8.0] is eligible but a pT stage ≥ pT3b is considered aggressive)
• Locoregional node involvement at radical prostatectomy (pN1)
• Persistently elevated PSA post-RP nadir (PEPP) defined as PSA > 0.1 ng/mL after radical prostatectomy
• Serum albumin ≥ 3.0 g/dL within 90 days prior to registration
• GFR >35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to registration.
• Serum total bilirubin ≤1.5 × ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject is eligible) within 90 days prior to registration.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN within 90 days prior to registration.
• Testosterone >50 ng/dL within 90 days prior to registration. Prior androgen deprivation (GnRH analog and/or non-steroidal antiandrogen) therapy is allowed provided that serum testosterone concentration must be ≥ 50 ng/dL prior to registration or starting ADT, whichever occurs first; 5-alpha reductase inhibitors will not impact eligibility, but must be discontinued prior to starting protocol treatment.
• History and physical with ECOG Performance Status 0-1 or within 90 days prior to registration.
• Definitive clinical or radiologic evidence of metastatic disease with the exception of locoregional lymph nodes.
• Prior invasive malignancy (except non-melanomatous skin cancer carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years).
• Prior systemic chemotherapy for the study cancer. Note: prior chemotherapy for a different cancer is allowable.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• History of any of the following:
• Documented inflammatory bowel disease
• Transmural myocardial infarction within the last 4 months prior to registration.
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 4 months prior to registration
• Seizure disorder or condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
• Uncontrolled hypertension defined as a sustained systolic blood pressure in excess of 150 mmHg or a sustained diastolic blood pressure in excess of 90 mmHg despite optimized antihypertensive therapy.
• Known gastrointestinal disorder affecting absorption of oral medications.
• Active uncontrolled infection defined as an identified infectious condition that requires active therapy that has not yet been completed.
• HIV positive patients with CD4 count < 200 cells/microliter within 30 days prior to registration OR HIV patients under treatment with highly active antiretroviral therapy (HAART) within 30 days prior to registration regardless of CD4 count. Note: HIV testing is not required for eligibility for this protocol as it is self-reported. This exclusion criterion is necessary because the treatments involved in this protocol may be immunosuppressive and/or interact with HAART.

• Willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPPA) authorization for the release of personal health information.
• Males aged 18 years of age and above
• Patients must have adenocarcinoma of the prostate gland
• Patients must have received primary treatment with radical prostatectomy.
• Patients must have evidence of biochemical (PSA) relapse after prostatectomy
• Patients must have PSA within study range
• Patients must have non-metastatic (M0) disease, as defined by a lack of metastases seen on CT scan of the chest/abdomen/pelvis and whole-body radionuclide 99Technetium (Tc) bone scan, (or sodium fluoride PET scan) taken within 3 months of study entry.
• Patients must have had node negative (pN0) disease found at the time of surgery.
• Patients must have non-castrate levels of serum testosterone levels within study range.
• Patients must not have previously received hormonal therapy (LHRH agonist, antiandrogen, or both), with the exception of neoadjuvant or adjuvant hormones given in conjunction with prostatectomy.
• Patients must have Eastern Cooperative Oncology Group (ECOG)performance status of 0-1, and life expectancy greater 3 years.
• Patients must have laboratory test results within the certain ranges
• Patients must be disease-free from prior malignancies for greater than 3 years, with the exception of non-melanoma skin cancers and superficial urothelial cancers.
• Patients must have the ability to swallow the study drug whole as a tablet or capsule.
• Throughout study, male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration or per local guidelines where these require additional description of contraceptive methods.
• Throughout the study, patients must use a condom if having sex with a pregnant woman.
• Currently active second malignancy
• Primary treatment with radiation therapy.
• Radiographic or clinical evidence of local-regional tumor recurrence,
• Concurrent use of other antiandrogens, estrogen-like agents, or 5a-reductase inhibitors.
• Use of systemic corticosteroids equivalent to prednisone (inhaled corticosteroids are permitted).
• Concurrent use of other anti-cancer agents or treatments.
• Serious concurrent medical illnesses (including uncontrolled major cardiac, pulmonary, Child-Pugh C liver or psychiatric diseases) or active major infections (including HIV, Hepatitis A-C).
• Clinically significant cardiovascular disease including:
• Myocardial infarction within 6 months of Screening visit.
• Uncontrolled angina within 3 months of Screening visit.
• Congestive heart failure (within certain ranges)
• History of clinically significant ventricular arrhythmias
• Prolonged corrected QT interval
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
• Hypotension within certain ranges
• Uncontrolled hypertension within certain ranges
• Medications which lowers seizure threshold.
• History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12months of enrollment (Day 1 visit).
• Patients taking medications that may have adverse interactions with enzalutamide

1. Patients must have the ability to understand and sign an approved ICF. 2. Patients must have the ability to understand and comply with all protocol requirements. 3. Patients must be ≥18 years of age. 4. Patients must have an ECOG performance status of 0 to 2. 5. Patients must have a life expectancy >6 months. 6. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer. 7. Patients must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader. 8. Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L). 9. Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone). 10. Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient has received only 1 taxane regimen, the patient is eligible if: a. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation, intolerance, etc.). 11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria: 1. Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL. 2. Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. 3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria, Scher et al 2016). 12. Patients must have ≥1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to beginning study therapy. 13. Patients must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.). 14. Patients must have adequate organ function: a. Bone marrow reserve:
• White blood cell (WBC) count ≥2.5 x 10^9/L (2.5 x 10^9/L is equivalent to 2.5 x 10^3/μL and 2.5 x K/μL and 2.5 x 10^3/cumm and 2500/μL) OR absolute neutrophil count (ANC) ≥1.5 x 10^9/L (1.5 x 10^9/L is equivalent to 1.5 x 10^3/μL and 1.5 x K/μL and 1.5 x 10^3/cumm and 1500/μL)
• Platelets ≥100 x 10^9/L (100 x 10^9/L is equivalent to 100 x 10^3/μL and 100 x K/μL and 100 x 10^3/cumm and 100,000/μL)
• Hemoglobin ≥9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L) b. Hepatic:
• Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases c. Renal:
• Serum/plasma creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min 15. Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L) [Inclusion #16 has been removed] 17. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. 18. For patients who have partners of childbearing potential: Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principle investigator during the study and for 6 months after last study drug administration. 19. The best standard of care/ best supportive care options planned for this patient: 1. Are allowed by the protocol 2. Have been agreed to by the treating investigator and patient 3. Allow for the management of the patient without 177Lu-PSMA-617 1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed. 2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to day of randomization. 3. Any investigational agents within 28 days prior to day of randomization. 4. Known hypersensitivity to the components of the study therapy or its analogs. 5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy. 6. Transfusion for the sole purpose of making a subject eligible for study inclusion. 7. Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast). 8. A superscan as seen in the baseline bone scan. 9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. 10. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. 11. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, superficial bladder cancer.

• Biopsy-confirmed diagnosis of primary or recurrent respective tumor type and scheduled to undergo surgical resection
• Part 1: Biopsy-confirmed diagnosis of head and neck squamous cell carcinoma (HNSCC) or breast cancer
• Part 2: Biopsy-confirmed diagnosis of HNSCC, breast cancer, colorectal cancer, prostate cancer, ovarian cancer, urothelial carcinoma and non-small cell lung cancer.
• Histologically diagnosed by an excisional biopsy procedure
• Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging would not be feasible
• Life expectancy <12 weeks
• Hepatic impairment (Child-Pugh score ≥5) or significant liver disease including active hepatitis or cirrhosis

Males one month to 21 years of age with: Painful acute scrotum or testis OR Abdominal pain (+/- nausea, vomiting) and waddling gait ("cowboy shuffle") from painful scrotum. Males with: Synchronous bilateral testicular torsion History of known testicular or scrotal surgery Current hernia or painless hydrocele Current obvious scrotal bug bites History of chronic respiratory, hematological or vascular problems that will affect total body tissue oxygenation levels (Home oxygen).

• Metastatic prostate cancer (hormone-sensitive, de novo, or castration resistant)
• Localized prostate cancer with Gleason score ≥8
• Rising PSA after prostatectomy or radiation with PSA doubling time ≤ 6 months
• Persistent PSA after prostatectomy for PSA ≥ 0.2 ng/mL observed in testing at least 1 week apart
• Prostate cancer diagnosed at age ≤ 55 years
• Prostate cancer and a personal history of prior malignancy that does not include non-melanoma skin cancer or superficial bladder cancer.
• Prostate cancer diagnosis (any grade/stage) or prostate biopsy with high grade PIN or small acinar proliferation and a family history potentially indicating a germline mutation (e.g. breast cancer diagnosed at age ≤ 50, ovarian, pancreatic, uterine, colorectal, prostate cancer or sarcoma, in one or more first or second-degree relatives)
• Previous cancer genetic testing or counseling, or prior germline multigene panel testing. Previous tumor sequencing is acceptable if no genetic counseling took place.
• Localized prostate cancer previously treated and in remission for > 2 years unless family history potentially indicates a germline mutation.
• Active hematologic malignancy (e.g. CLL)

• Men with suspected but undiagnosed prostate cancer
• To be scheduled/scheduled for biopsy as routine clinical care
• Inability to obtain blood and urine per SOP or conduct an attentive DRE
• Unable to undergo/tolerate a prostate MRI or failure to conduct the MRI
• Prior diagnosis of prostate cancer
• Prior prostate MRI
• Participating in clinical trial for prostate disease
• Prior prostate surgery such as TURP, TUNA, TUMT, HOLEP, REZUM, UROlift
• Prior PCA3, TMPRSS2:erg or MIPS panel performed for clinical purpose