NEW YORK (GenomeWeb) – A team at the Karolinska Institute will use a new SEK 28 million ($3 million) research grant to further develop a multi-omic prostate cancer test, as well as to design follow-on diagnostics to help treat patients with the disease.
The blood-based test, called Stockholm3, consists of a panel of protein and genetic markers, and is already offered at the Karolinska as a laboratory-developed test for identifying men at greater risk of developing aggressive prostate cancer.
With the new funding, made available from the Erling-Persson Family Foundation, the researchers aim to further validate Stockholm3 in new cohorts, to expand the number of markers on the panel, and to develop a next-generation sequencing-based prognostic test to improve the treatment of metastatic cancer.
"By combining genomics, proteomics, and imaging we have the tools to dramatically improve prostate cancer diagnostics," said Henrik Grönberg, a professor of cancer epidemiology at the Karolinska who is overseeing the project.
The official title of the effort is the "Individualized Prostate Cancer Diagnosis Pipeline," and the funding should cover all research costs over the next three years, Grönberg told GenomeWeb.
In addition to Grönberg's group, partners involved include Karolinska University Hospital, Stockholm City Council, and Prostate Cancer UK.
The latter is expected to commence its own evaluation of the Stockholm3 test in a cohort of 10,000 men, a fifth of whom will be of African descent, in the British healthcare system next year. Grönberg said that similar validation studies are planned in Belgium, Germany, the Netherlands, and Norway in the next two years.
"There is a strong international interest for the Stockholm3 test both from research groups who want to validate the test in their healthcare environments and from lab providers," said Grönberg.
That includes interest from US players such as Kaiser Permanente and the Prostate Cancer Foundation among others, he said.
All of the information gleaned from these various studies will be filtered into Karolinska's effort to build a diagnostic toolbox centered on Stockholm3. The test relies on five protein biomarkers, 100 SNPs, and clinical data to determine a single score that measures the risk of having aggressive prostate cancer, defined as a Gleason score of at least 7.
"For the patient, it is a simple blood test, just like the [prostate-specific antigen] test," Grönberg said.
Between 2012 and 2014, the test was evaluated in a cohort of 60,000 men in the Stockholm metropolitan region. The results of of the so-called STHLM3 trial were described in The Lancet Oncology last year. By using Stockholm3, investigators were able to increase the detection of aggressive cancers by 20 percent, and at the same time reduce unnecessary biopsies by half compared to clinical practice. They were also able to detect aggressive cancers in patients with low PSA concentrations.
Since then the test has become available as an LDT through Karolinska University Hospital. Grönberg said that the Swedish National Board of Health and Welfare is currently evaluating the Stockholm3 for use in a national screening program.
Karolinska uses Thermo Fisher Scientific products to perform the Stockholm3 test. Grönberg noted that his group has "worked closely" with Thermo Fisher to develop the test, and previously described the partnership as a "a close collaboration with joint development teams and problem solving and sharing of knowledge."
The genetic component of Stockholm3 is carried out using Thermo Fisher's QuantStudio 12K Flex Real-Time PCR System, a desktop unit that enables quantitative PCR analysis in around 20 minutes. The plasma protein analysis component of Stockholm3 is conducted using Thermo Fisher's ImmunoCAP ISAC, a biochip-based immunoassay platform.
Thermo Fisher will work toward commercializing a Stockholm3 test kit in the future, Grönberg noted.
He acknowledged that other blood-based multiplex tests for prostate cancer do exist, but said that they do not include genetic markers and have not been validated prospectively in a large cohort.
Though he did not name competitive panels, blood-based assays for determining prostate cancer aggressiveness include several focused on the biomarker AR-V7. Cambridge, Massachusetts-based Exosome Diagnostics recently launched a urine-based test for gauging tumor aggressivity in patients.
Test pipeline
With the new funding, Grönberg said his team should be able to achieve four main objectives. The first is to validate Stockholm3 in a non-Caucasian population. He said the partnerships with Prostate Cancer UK, as well as the other projects planned elsewhere in Europe, should advance this goal.
Grönberg's team may also expand the test itself as information from these studies is generated. Other research groups have suggested adding markers to Stockholm3, as well, and the Karolinska has even put in place a process for evaluating these markers using its internal biobank.
The team is also interested in combining Stockholm3 with magnetic resonance imaging followed by targeted biopsies. "Our hypothesis is that the Stockholm3 test together with MRI will further increase the detection of clinically significant cancer," said Grönberg.
The group is currently running a feasibility study based on 800 MRIs, and will soon commence a larger, 10,000-cohort randomized controlled trial. If the findings are positive, Karolinska will begin using Stockholm3 in conjunction with MRI in 2018.
A prognostic sequencing-based test connected to Stockholm3 is also envisioned.
"There is a great need for prognostic markers and we believe that genomic markers analyzed from a biopsy can be an option," he said.
To develop the test, Grönberg will rely on tools developed via the Clinical Sequencing of Cancer in Sweden project (ClinSeq), which he directs. Established in 2013, ClinSeq is engaged in building infrastructure for genomic profiling in cancer, with an eye toward designing new genomics-based tests. According to Grönberg, the ClinSeq profile consists of sequencing all 650 genes associated with cancer, as well as carrying out RNA-seq to estimate the expression levels of all 20,000 human genes.
Grönberg said that his team will assess approximately 2,000 samples, followed by a prospective validation study. Based on the results of that analysis, Grönberg's team will develop a condensed, "cost-efficient profile" for prostate cancer biopsies that can later be implemented clinically.
"The idea is to develop a genomic scoring of the tumor characteristics that can complement Gleason scoring," he said.
Prostate cancer is the most common form of cancer in Sweden with over 10,000 cases and 2,500 deaths annually, Grönberg noted. These new tests should help to identify and treat those suffering from aggressive cancer, improving health and reducing mortality.