Detecting tumor DNA in blood of men with high-risk localized prostate cancer

Circulating Tumor DNA in High Risk Localized Prostate Cancer

This study will test whether a tumor-informed blood test can detect circulating tumor DNA before prostatectomy in men with high-risk localized prostate cancer.

Quick facts

• Study type: Observational
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: University of Pittsburgh (other)
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT07222436 on ClinicalTrials.gov

What this trial studies

This prospective, non-therapeutic biomarker study will collect serial blood samples from men with high-risk localized prostate cancer prior to prostatectomy and compare plasma circulating tumor DNA (ctDNA) to tumor tissue. Tumor-informed sequencing using the SaferSeqS assay will use DNA alterations identified from prostatectomy specimens to sensitively detect ctDNA in plasma. The study will enroll a pilot cohort of about 12–24 patients and apply an adaptive statistical design to evaluate ctDNA abundance and molecular characteristics. Results will characterize how often and in what molecular form ctDNA is detectable preoperatively and inform feasibility for larger studies.

Who should consider this trial

Good fit: Ideal candidates are men aged 18 or older with histologically confirmed high-risk localized prostate adenocarcinoma (e.g., clinical stage ≥ cT3a, Grade Group 4–5, or PSA ≥20) who are scheduled for prostatectomy, have ECOG 0–1, and are willing to provide blood and tumor tissue.

Not a fit: Patients with low-risk disease, those not undergoing prostatectomy, or tumors that do not shed detectable ctDNA are unlikely to receive direct clinical benefit from this non-therapeutic study.

Why it matters

Potential benefit: If successful, this approach could enable earlier detection of tumor-derived DNA and help improve postoperative risk stratification and decisions about additional therapy.

How similar studies have performed: Tumor-informed ctDNA methods such as SaferSeqS have shown high sensitivity in prior work, but detecting ctDNA before prostatectomy in localized prostate cancer remains challenging and less well-established.

Eligibility criteria

Inclusion Criteria:

1. Must have histologically confirmed prostate cancer.
2. Age ≥ 18 years.
3. ECOG performance status of 0-1.
4. Must have the ability to understand and the willingness to sign a written informed consent document.
5. Willing to provide serial blood samples for the study.
6. 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.
7. 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.
8. 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:

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

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Where this trial is running

Pittsburgh, Pennsylvania

• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Leonard J Appleman, MD, PhD — UPMC Hillman Cancer Center
• Study coordinator: Brieanna Marino, MS

Conditions: Prostate Cancer, prostatectomy, ctDNA