NEW YORK (GenomeWeb) – A prospective, population-based study in Stockholm has shown that a prostate cancer screening method combining plasma protein biomarkers, genetic polymorphisms, and clinical variables may reduce the overdiagnosis that can occur with standard prostate-specific antigen screening.
The study was the result of an ongoing research collaboration between Thermo Fisher Scientific and Henrik Grönberg in Karolinska Institute's department of medical epidemiology and biostatistics.
In the study, published online today in Lancet Oncology, the researchers noted that the screening assay was significantly better than PSA alone for detecting cancers with a signature of high risk, a Gleason score of at least 7.
The assay includes detection of the plasma protein biomarker PSA and five other proteins, as well as qPCR genotyping for a panel of 232 polymorphisms associated with prostate cancer, and clinical variables such as age and family history.
To select the patients, the authors used a tax register to randomly contact Swedish men ages 50 to 69 and invite them for screening. The assessment method — called Stockholm 3, or the STHLM3 model — was compared to PSA alone on training and validation samples of 11,130 men and 47,688 men respectively.
Ultimately, the authors projected that the screening method could reduce the number of biopsies by about a third and could avoid 44 percent of benign biopsies.
They further noted that a 30 percent reduction in prostate biopsies would equate to about 300,000 fewer procedures annually in the US, and yet the method could still identify clinically significant cancers in men with low PSA concentrations.
"Extremely large, prospective trials like this are rare for biomarkers," Jim Godsey, vice president of R&D for clinical next-generation sequencing and oncology, a new business at the Thermo Fisher, told GenomeWeb in an interview.
The STHLM3 test has commercial potential, but Godsey said the project is still in the translational research phase. He added that Thermo Fisher created the clinical sequencing business about a month ago, and this test is representative of investment and an IVD focus in oncology.
Henrik Grönberg told GenomeWeb in an email that when his group started planning the STHLM3 study in 2011 it was looking for protein and genetic platforms that met requirements for turnaround time, plasma and DNA volumes needed, and cost per sample.
"We soon realized that Thermo Fisher Scientific, which had a location in Uppsala, had an excellent multiplex technology that could be adapted and used for our needs in cancer," Grönberg said, adding that the group selected the QuantStudio 12K Flex Real-Time PCR system from Thermo Fisher because it is "flexible, fast, and easy to use." For the protein detection aspect of the study, the group used the firm's ImmunoCAP ISAC, a biochip-based immunoassay platform.
Grönberg described the work with Thermo Fisher as "a close collaboration with joint development teams and problem solving and sharing of knowledge."
The STHLM3 test will be available as a laboratory developed test in Sweden in March 2016, Grönberg said.
He noted that the researchers have been contacted by groups and organizations in several other countries who are interested in validating the test in their respective geographies and clinical settings. "The research collaboration with Thermo Fisher makes it easy to collaborate across the globe," he added.
The QuantStudio 12K Flex was originally launched by Thermo Fisher brand Life Technologies in late 2011. It is a research-use-only system that can run high numbers of targets with a flexible configuration, Elliot Shelton, director of product management for genetic science at Thermo Fisher, told GenomeWeb in an interview.
One of the main features of the platform is the capability to run OpenArray plates, which are the firm's nanofluidic qPCR technology. "It is a very flexible system — for the OpenArray format there are 11 different configurable formats, so you can go from anywhere down to 16 targets of interest up to 256," Shelton explained.
Users can customize the qPCR arrays by selecting from approximately 9 million pre-designed SNP assays, and the company can also design custom assays, such as the one used in the Karolinska study. The plates are manufactured on site at Thermo, with sample and master mix added by the user, Shelton said.
But a main differentiator of the QuantStudio 12K Flex system, Shelton noted, is that it uses removable blocks, so a researcher can use 96-well plates or OpenArray plates, which can do roughly 12,000 qPCR reactions per run.
Because of this flexibility in configuring the system, costs vary. For the OpenArray-enabled version, it is something less than $200,000, he said. The firm does not share pricing for the plates, but Shelton noted that the nanofluidic reaction size allows for minimal reagent usage, making large-scale projects like the Karolinska study more cost-effective.
Since its launch, there have been 190 publications using the OpenArray technology, and the firm's website has a sortable, filterable list of these to assist researchers, Shelton further said.
Thermo will now continue to work toward commercializing the prostate cancer screening assay. "The benefit of providing our tools, and sometimes having a wonderful result like this with Dr. Grönberg, is to then be able to commercialize it and create an FDA-approved product that has an impact on men worldwide," Thermo's Godsey said.