CTC Immune Checkpoint

Patients will be eligible for inclusion in this study only if all of the following criteria
apply:

1. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Small cell or
neuroendocrine tumors of the prostate are also permitted.

2. Clinical or radiographic evidence of progressive metastatic disease, with progression
defined as a rising PSA, new metastatic lesions (bone or soft tissue), or radiographic
evidence of tumor growth on CT or MRI.

3. Age ≥ 18 years.

4. Ability to understand and the willingness to sign a written informed consent document.

In addition to meeting all of the above criteria, patients must meet all of the criteria
for one of the following groups:

A) mCRPC starting sipuleucel-T (Provenge) with or without abiraterone acetate or
enzalutamide

1. For patients with adenocarcinoma of the prostate (not applicable for patients with
small cell or neuroendocrine tumors of the prostate, or those receiving ADT therapy):
Castrate levels of testosterone (≤ 50 ng/dl)

2. Patient planning to start sipuleucel-T.

3. Enrollment prior to the initiation of sipuleucel-T.

B) mCRPC with visceral or high risk disease pre-abiraterone/enzalutamide

1. For patients with adenocarcinoma of the prostate (not applicable for patients with
small cell or neuroendocrine tumors of the prostate, or those receiving ADT therapy):
Castrate levels of testosterone (≤ 50 ng/dl)

2. Visceral OR high risk disease - must meet one of the following categories:

- Visceral disease: Radiographic evidence of liver, adrenal, pulmonary, or brain
metastases

- High risk disease: Presence of at least 2 of the following factors:

- Bone pain requiring opioids

- Anemia (Hgb <13 g/dL)

- Bone scan progression at baseline

- >2 sites of metastatic disease

- Karnofsky Performance Status (KPS) ≤ 70

- PSA doubling time <3 months

3. Patient planning to start abiraterone acetate or enzalutamide.

4. Enrollment prior to the initiation of abiraterone acetate or enzalutamide.

C) Newly diagnosed metastatic castration sensitive prostate cancer (mCSPC) starting
androgen deprivation therapy

1. Evidence of metastatic disease on radiographic imaging

2. Enrollment within 2 weeks of initiation of androgen deprivation therapy (ADT).

3. Lack of history of hypogonadism

D) Enzalutamide or abiraterone acetate resistant mCRPC

1. For patients with adenocarcinoma of the prostate (not applicable for patients with
small cell or neuroendocrine tumors of the prostate, or those receiving ADT therapy):
Castrate levels of testosterone (≤ 50 ng/dl)

2. Evidence of disease progression on or following enzalutamide or abiraterone acetate,
as defined by one of the following:

- Radiographic evidence of disease progression as defined by new bone scan lesions
or growth of existing soft tissue/visceral/lymph node/bone metastases as
determined by the investigator

- Clinical progression of disease with cutaneous lesions or palpable lesions in
absence of radiographic progression

Exclusion Criteria:

1. History of intercurrent or past medical or psychiatric illness that would make
participation in a blood drawing protocol difficult or not feasible at the discretion
of the principal investigator or co-investigator(s).

2. Treatment with an anthracycline (including mitoxantrone) within 1 week of CTC
collection, as anthracyclines cause auto-fluorescence of cells.