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Clinical determinants for successful circulating tumor DNA analysis in prostate cancer
Author(s) -
Schweizer Michael T.,
Gulati Roman,
Beightol Mallory,
Konnick Eric Q.,
Cheng Heather H.,
Klemfuss Nola,
De Sarkar Navonil,
Yu Evan Y.,
Montgomery R. Bruce,
Nelson Peter S.,
Pritchard Colin C.
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23778
Subject(s) - prostate cancer , somatic cell , germline mutation , germline , medicine , adenocarcinoma , prostate , oncology , cancer , biology , pathology , mutation , cancer research , gene , genetics
Background Plasma‐based cell‐free DNA is an attractive biospecimen for assessing somatic mutations due to minimally‐invasive real‐time sampling. However, next generation sequencing (NGS) of cell‐free DNA (cfDNA) may not be appropriate for all patients with advanced prostate cancer (PC). Methods Blood was obtained from advanced PC patients for plasma‐based sequencing. UW‐OncoPlex, a ∼2 Mb multi‐gene NGS panel performed in the CLIA/CAP environment, was optimized for detecting cfDNA mutations. Tumor tissue and germline samples were sequenced for comparative analyses. Multivariate logistic regression was performed to determine the clinical characteristic associated with the successful detection of somatic cfDNA alterations (ie detection of at least one clearly somatic PC mutation). Results Plasma for cfDNA sequencing was obtained from 93 PC patients along with tumor tissue ( N = 67) and germline ( N = 93) controls. We included data from 76 patients (72 prostate adenocarcinoma; 4 variant histology PC) in the analysis. Somatic DNA aberrations were detected in 34 cfDNA samples from patients with prostate adenocarcinoma. High PSA level, high tumor volume, and castration‐resistance were significantly associated with successful detection of somatic cfDNA alterations. Among samples with somatic mutations detected, the cfDNA assay detected 93/102 (91%) alterations found in tumor tissue, yielding a clustering‐corrected sensitivity of 92% (95% confidence interval 88‐97%). All germline pathogenic variants present in lymphocyte DNA were also detected in cfDNA ( N = 12). Somatic mutations from cfDNA were detected in 30/33 (93%) instances when PSA was >10 ng/mL. Conclusions Disease burden, including a PSA >10 ng/mL, is strongly associated with detecting somatic mutations from cfDNA specimens.