Blood, Sweat and Tears: the liquid biopsy penetrates early detection

Pathologists have obviously been involved in early detection of cancer for decades.  The Pap test and HPV testing have dramatically reduced cervical cancer incidence in the US and PSA blood testing has played a significant, if controversial, role in prostate cancer screening.  But lab-based early detection of many cancers, such as pancreatic and ovarian, has remained elusive, resulting in many patients presenting at advanced stages. Detection of circulating tumor cells and circulating DNA (ctDNA) has prompted excitement, and may still play important roles in therapeutic monitoring of advanced cancers, but their utility for localized cancers may be limited.

file000709986619However, a recent report from some of my previous colleagues at Johns Hopkins has demonstrated encouraging sensitivity of a multi-analyte blood test for the detection of several types of non-metastatic cancers.  The new blood test, termed CancerSEEK, utilizes combined assays for genetic alterations and protein biomarkers.  The genetic alterations are assessed by a sensitive multiplex-PCR using a 61-amplicon panel that includes somatic mutations in 16 genes (TP53, KRAS, PIK3CA, etc.) commonly altered in the target cancers (ovary, pancreas, liver, stomach, esophagus, colorectum, lung and breast).  In addition to ctDNA the assay also targeted 8 plasma proteins (CA-125, CEA, etc.) previously found to be important in cancer detection.

This assay was then tested in over 1000 patients with Stage I to III cancers.  Sensitivity of detection ranged from 98% for ovarian cancers to 33% for breast cancers.  The specificity was also high, with only 7 of 812 individuals without cancer scoring positive.  The strength of this assay likely lies in its unique combination (and algorithmic analysis) of protein and genetic biomarkers.  These investigators estimate the price of such a test to be approximately $500.  Of course one important caveat to this study is that these patients were already diagnosed with cancer, so expansion of clinical trials to completely asymptomatic patients will be important.  Also, the sensitivity for the ideal targets, the Stage I cancers, was significantly lower (43%) than higher stage tumors.

Enthusiasm for sensitive screening tests should be balanced by the recognition that they pose the risk of prompting unnecessary biopsies and creating concern among our patients.

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