Circulating Tumor DNA in High Risk Localized Prostate Cancer

The Vogelstein lab has developed a highly sensitive, tumor-informed method of detecting circulating free DNA (cfDNA) shed by solid tumors. Plasma will be assayed for ctDNA using the SaferSeqS tumor-informed assay, employing DNA sequences derived from prostatectomy specimens. The abundance and molecular characteristics of ctDNA will be evaluated for a pilot group of 12-24 patients using an adaptive statistical design.

Inclusion criteria

• Must have histologically confirmed prostate cancer.
• Age ≥ 18 years.
• ECOG performance status of 0-1.
• Must have the ability to understand and the willingness to sign a written informed consent document.
• Willing to provide serial blood samples for the study.
• Willing to provide tumor tissue (prostatectomy for primary cohort; prostatectomy or biopsy for exploratory cohort) for correlative studies which will compare ctDNA to tumor specimens.
• Primary Cohort: High-risk localized prostate adenocarcinoma defined as one or more of the following:

o Clinical stage ≥ cT3a, Grade Group 4 or 5 (Gleason sum 8-10), and PSA ≥ 20

*Non-bulky pelvic lymphadenopathy and indeterminate findings on staging imaging (CT, bone scan, PSMA PET CT) are allowed if the surgeon believes RP is appropriate.

• Exploratory Cohort: Men with a diagnosis of prostate adenocarcinoma and one of the following:

• Localized prostate adenocarcinoma on active surveillance
• Biochemically-recurrent prostate adenocarcinoma after definitive local therapy
• Hormone-sensitive, metastatic prostate adenocarcinoma
• Metastatic CRPC

Exclusion criteria

• History of another primary cancer within the last 3 years, except for non-melanomatous skin cancer.
• Receiving androgen deprivation or other systemic therapy for prostate cancer.
• Medical condition or social situation that may preclude adherence to the protocol.

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