Andrew Bowser is a medical writer based in Brooklyn, New York.
The findings “[raise] the specter that patients could potentially receive different treatments depending on the cell-free DNA platform,” authors of a recent research letter write.
Two commercially available blood specimen tests have shown low congruence for tumor-specific alterations, according to authors of a recently published analysis including 40 paired samples from patients with metastatic prostate cancer.
Despite the limited sample size, the data suggest that gene alterations reported by so-called “liquid biopsy” tests will be different across platforms, “raising the specter that patients could potentially receive different treatments depending on the cell-free DNA (cfDNA) platform,” the authors wrote in a research letter published online in JAMA Oncology (Dec. 14, 2017).
Individually, the two liquid biopsy tests both have “self-reported high accuracy, specificity, and sensitivity to specifically detect and quantify tumor-specific alterations,” wrote co-authors Gonzalo Torga, MD, and Kenneth J. Pienta, MD, of the James Buchanan Brady Urological Institute at Johns Hopkins School of Medicine, Baltimore.
The initial intention of the study was to find the best commercial lab to test samples for metastatic prostate cancer patients, Dr. Torga said in an interview with Urology Times.
However, “when we compared the results, we were stricken by the discordance, and we believed it was very important to share our data with the medical community,” Dr. Torga said of the study, which is believed to be the first to compare two liquid biopsy providers in the clinical setting.
Of 34 evaluable patient specimens, only nine (35%) showed complete congruence between the two assays, which included Guardant360 (Guardant Health, Inc.) and PlasmaSELECT (Personal Genome Diagnostics Inc.), the authors said in their report.
Among the remaining 25 specimens, investigators said they found partial congruence in six, and no congruence in 16.
These findings are “disturbing,” Daniel F. Hayes, MD, said in an accompanying editorial published online in JAMA Oncology (Dec. 14, 2017).
“The Torga and Pienta study offers an important note of caution, and we should all pay attention,” wrote Dr. Hayes, of the University of Michigan Comprehensive Cancer Center, Ann Arbor.
In his editorial, Dr. Hayes said that he would continue to call for “collegial and constructive” measures” to improve biomarker tests in general: “I recognize the important contributions to patient care provided by many laboratory-developed tests, but I also fear that there are many tests performed every day across our country in which clinicians assume, but cannot be certain, of their accuracy and basis for use.”
However, Dr. Torga told Urology Times that the results of his study suggest “the same blood might give different results depending on the platform to where the blood is submitted.”
This finding raises the possibility that patients could potentially be managed differently depending on which platform is used, according to Dr. Torga. For example, research suggests metastatic, castration-resistant prostate cancers with genomic aberrations that interfere with DNA repair (e.g., BRCA1/2) may be sensitive to poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors.
“However, if results from cfDNA testing are giving us a false positive for alterations in these DNA-repair genes, we would be preventing these patients from getting another therapy or enrolling a clinical trial,” Dr. Torga said.
To move forward in precision medicine, the certification process for cfDNA technologies should be reevaluated, according to Dr. Torga.
“This technology has a great potential to help the way we treat our patients, but in my opinion, it needs more time to be optimized for its use as standard of care,” he explained.
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