Must have undergone bilateral orchiectomy (surgical castration) or be willing to continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical castration)
Ongoing androgen deprivation therapy with a GnRH analogue, GnRH antagonist, or bilateral orchiectomy
On Androgen Deprivation Therapy (ADT) with a Gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy. All patients will be required to be on ADT throughout the study;
Testosterone <  ng/dL; patients must continue primary androgen deprivation with an gonadotrophin releasing hormone (LHRH) analogue if they have not undergone orchiectomy
Ongoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy, with serum testosterone <=  ng/dL (<= . nmol/L) within  days before randomization
Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); patients who have not had an orchiectomy must maintain effective GnRH-analogue therapy for the duration of the trial
Patients with prostate cancer can continue to receive treatment with gonadotropin releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on therapy
Patients must have undergone bilateral surgical castration or must continue on gonadotrophin releasing hormone (GnRH) agonists/antagonists for the duration of the study.
Concurrent use of gonadotrophin releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening <  ng/dL
Patients must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy; (patients with a malignancy other than prostate cancer are excluded from this criterion)
Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy
More than  months of prior ADT with gonadotrophin releasing hormone (GnRH) antagonist/agonist at time of consent. Bicalutamide given for =<  months at the time of registration as flare prevention is allowed
Orchiectomy
Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy
Patients must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy
Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration).
Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration)
GNRH agonists or GNRH antagonists (e.g., leuprorelin, degarelix) for >  months prior to consenting
Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy
mCRPC EXPANSION COHORT: Patients must have undergone bilateral surgical castration or must agree to continue on gonadotrophin releasing hormone (GnRH) agonists/antagonists for the duration of the study
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
Castrate-resistant disease, defined as follows:\r\n* All patients must have received (and be receiving) standard of care androgen deprivation treatment (surgical castration versus gonadotropin-releasing hormone [GnRH] analogue or antagonist treatment); subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study\r\n* Patients may or may not have been treated previously with a nonsteroidal antiandrogen; for patients previously treated with an antiandrogen, they must be off use of anti-androgen for at least  weeks (for flutamide) or  weeks (for bicalutamide or nilutamide) prior to registration; moreover, subjects who demonstrate an anti-androgen withdrawal response, defined as a >= % decline in PSA within - week of stopping a nonsteroidal antiandrogen, are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal\r\n* Patients must have a castrate serum level of testosterone (<  ng/dL) within  weeks of day 
Prior surgical castration or concurrent use of gonadotropin-releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening <  ng/dL
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
Pre/perimenopausal women with a known hypersensitivity to gonadotrophin releasing hormone (gnRH).
Patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on therapy
Castration resistant disease defined as ongoing androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy and serum testosterone level ? . nmol/l ( ng/dL) at screening visit. Individuals who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial.
Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration);
Ongoing androgen deprivation therapy (ADT) with a Gonadotropin-releasing hormone (GnRH) analogue or a surgical/medical castration with testosterone level of ?.nmol/L (ng/dL)
Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone analog or inhibitor, or orchiectomy (surgical or medical castration)
Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least  days prior to Day  of Cycle ) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin
Ongoing androgen depletion therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
All patients who have not initiated hormone therapy (early induction patients) must have elevated PSA >=  ng/ml within  days prior to registration; for late induction registrations, PSA must be >=  ng/ml prior to start of androgen deprivation therapy; either antiandrogen or LHRH analogue or gonadotropin-releasing hormone (GNRH) antagonist; if patients are on antiandrogen, this will need to be discontinued for at least  days prior to registration
COHORT A: More than  months of prior hormonal therapy (e.g., gonadotropin hormone releasing analogs, megestrol acetate, or Casodex); there is no washout period required for gonadotropin hormone releasing (GnRH) analogs; a two week washout period is required for megestrol or anti-androgen
Patients must agree to continue androgen deprivation therapy with a GnRH agonist/antagonist throughout the study or have had a prior bilateral orchiectomy
Subject has ongoing androgen deprivation therapy with a Gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) or bilateral orchiectomy (i.e., surgical or medical castration).
For subjects who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the study.
Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration)
Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy
Castrate levels of testosterone (testosterone <  ng/dL) on androgen deprivation therapy (ADT). Patients who have not undergone orchiectomy will continue gonadotropin releasing hormone (GnRH) agonist or antagonist therapy.
Castrate-resistant disease, defined as follows:\r\n* All patients must have received standard of care androgen deprivation treatment before trial entry (surgical castration versus gonadotropin-releasing hormone [GnRH] analogue or antagonist treatment), and subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study\r\n* Patients may have been treated previously with a nonsteroidal antiandrogen, with evidence of disease progression subsequently; subjects must be off use of anti-androgen for at least  weeks (for flutamide) or  weeks (for bicalutamide or nilutamide) prior to registration\r\n** Subjects who demonstrate an anti-androgen withdrawal response, defined as a >= % decline in PSA within - week of stopping a nonsteroidal antiandrogen are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal\r\n* Castration levels of testosterone (<  ng/dL) within  weeks of registration
Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy (i.e., surgical or medical castration)
Patients currently being treated with a gonadotropin-releasing hormone (GnRH agonist), bicalutamide or with bisphosphonates may continue treatment while on clinical trial PU-H as long as the treatment has been initiated before the study start; GnRH agonist must have been well tolerated for at least three months
Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy
Is willing to maintain androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy; The exclusion criteria apply only to patients starting new treatment with enzalutamide after receiving placebo as randomized treatment. Each patient must not meet any of the following criteria:
Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
Ongoing monthly gonadotrophin releasing hormone (GNRH) agonist is required in pre-menopausal women or male participants for at least  weeks prior to study entry
Ongoing androgen depletion therapy with a gonadotropin-releasing hormone (GnRH) analog or inhibitor, or orchiectomy (i.e., surgical or medical castration). Note: patients who have not undergone orchiectomy must continue GnRH analog therapy for the duration of this protocol.
CRPC participants must maintain ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing serum testosterone is < ng/dL (<. nmol/L)
Patients who have not had a bilateral orchiectomy must have a plan to maintain effective GnRG-analogue therapy for the duration of the trial
Ongoing androgen deprivation therapy with an gonadotropin releasing hormone (GnRH) analogue or prior bilateral orchiectomy (medical or surgical castration). For patients who have not had bilateral orchiectomy, there must be a plan to maintain effective GnRH-analogue for the duration of the trial.
Subjects who are currently on gonadotropin-releasing hormone (GnRH) agonists or antagonist therapy must continue androgen suppression
Patients must have castrate levels of testosterone (<  ng/dL) on gonadotropin-releasing hormone (GnRH) analogues or have had prior orchiectomy; GnRH analogues must be continued while on study
Patients with prostate cancer must continue to receive gonadotropin-releasing hormone (GnRH) agonist therapy (unless orchiectomy has been done); if a patient has refused GnRH therapy, they may be enrolled on a dose level for which the safety has already been determined
a GnRH analog is permitted if the patient had progressive disease on a GnRH (Gonadotropin-Releasing Hormone) analog plus a SERM (Selective Estrogen Receptor Modulators) or an AI; the GnRH analog may continue but the SERM or AI must be discontinued.
Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists or high dose bicalutamide within  month of enrollment unless serum testosterone is within normal limits
Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration);
A history of orchiectomy
Planned treatment with castration therapy (gonadotropin-releasing hormone [GnRH] agonist/antagonist) for >=  months
Post-menopausal status, as defined by institutional guidelines; concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed
Be on androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy; all patients will be required to be on ADT during the study period
Currently on therapy aimed at lowering testosterone levels (includes gonadotropin-releasing hormone [GnRH] agonist/antagonist, prior bilateral orchiectomy, oral anti-androgens, or -alpha reductase inhibitors); testosterone replacement is allowed but treatment should be stable during the entire study
Use of aromatase inhibitors, gonadotropin-releasing hormone (GNRH)-agonists i.e. Lupron, Zoladex within the last  months
Be planning to begin a course of at least  months of ADT; the ADT is defined as: (a) surgical castration; (b) gonadotropin-releasing hormone (GNRH) antagonist alone; (c) GNRH antagonist with oral androgen receptor blockade, and (d) GNRH antagonist, oral androgen receptor blockade, and -alpha reductase inhibitors; we will not include men with only oral anti-androgen therapy such as -alpha reductase inhibitors alone or oral anti-androgens alone
For part  of the study: plans to initiate castrating therapy (with a gonadotropin-releasing hormone [GnRH] antagonist, GnRH agonist, or orchiectomy); an antiandrogen may be started after initial imaging but cannot be used prior to baseline imaging; an antiandrogen is allowed but not required