Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer.

Despite decreased screening-based detection of clinically insignificant tumors, most diagnosed prostate cancers are still indolent, indicating a need for better strategies for detection of clinically significant disease before treatment. We hypothesized that patients with detectable circulating tumor DNA (ctDNA) were more likely to harbor aggressive disease. We applied ultra-low-pass whole-genome sequencing to profile cell-free DNA from 112 patients diagnosed with localized prostate cancer and performed targeted resequencing of plasma DNA for somatic mutations previously identified in matched solid tumor in nine cases. We also performed similar analyses of data from patients with metastatic prostate cancer. In all cases of localized prostate cancer, even in clinically high-risk patients who subsequently had recurrent disease, ultra-low-pass whole-genome sequencing and targeted resequencing did not detect ctDNA in plasma acquired before surgery or before recurrence. In contrast, using both approaches, ctDNA was detected in patients with metastatic prostate cancer. Our findings demonstrate clear differences between localized and advanced prostate cancer with respect to the dissemination and detectability of ctDNA. Because allele-specific alterations in ctDNA are below the threshold for detection in localized prostate cancer, other approaches to identify cell-free nucleic acids of tumor origin may demonstrate better specificity for aggressive disease.

Déclaration de conflit d'intérêts

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-centerc. Olga S. Voznesensky Employment: Novartis (I) Nicole V. Carrabba Employment: EMD Serono (I) Travel, Accommodations, Expenses: EMD Serono (I) David J. Einstein Research Funding: Trovagene (Inst), Bristol-Myers Squibb (Inst) James L. Gulley Research Funding: EMD Serono (Inst), Bavarian Nordic (Inst), Astellas Medivation (Inst), Pfizer (Inst), NantBioScience (Inst), Bristol-Myers Squibb (Inst), Merck (Inst) Steven P. Balk Stock and Other Ownership Interests: NKT Therapeutics Honoraria: Janssen Consulting or Advisory Role: Sanofi, Kronos, Constellation Pharmaceuticals, Janssen Biotech Patents, Royalties, Other Intellectual Property: License to NKT Therapeutics for an antibody Expert Testimony: Astellas Medivation Travel, Accommodations, Expenses: Janssen Huihui Ye Consulting or Advisory Role: Janssen No other potential conflicts of interest were reported.