Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer

Area of Science:

• Oncology
• Genetics
• Molecular Diagnostics

Background:

• Most prostate cancer diagnoses are indolent, necessitating improved methods for detecting clinically significant disease.
• Circulating tumor DNA (ctDNA) holds potential for non-invasive cancer detection.

Purpose of the Study:

• To investigate the detectability of ctDNA in patients with localized and metastatic prostate cancer.
• To determine if ctDNA can identify aggressive prostate cancer before treatment.

Main Methods:

• Ultra-low-pass whole-genome sequencing of cell-free DNA from 112 localized prostate cancer patients.
• Targeted resequencing of plasma DNA for known somatic mutations.
• Analysis of ctDNA in patients with metastatic prostate cancer.

Main Results:

• ctDNA was not detected in plasma from localized prostate cancer patients, including high-risk cases with recurrence.
• ctDNA was successfully detected in patients with metastatic prostate cancer using both sequencing methods.

Conclusions:

• Significant differences exist in ctDNA dissemination and detectability between localized and advanced prostate cancer.
• Current ctDNA detection methods are below the sensitivity threshold for localized prostate cancer.
• Alternative approaches may be required to identify cell-free nucleic acids specific to aggressive localized disease.