Precision medicine: diagnostic test for metastatic prostate cancer transitions from research to application

Karolinska University Hospital in Sweden now offers routine diagnostic testing of cell-free DNA in patients with metastatic prostate cancer. Researchers at Karolinska Institutet and SciLifeLab developed the test, now also available to hospitals across the Nordic region, potentially broadening treatment options for more patients with mutations in certain genes.

SciLifeLab researcher Johan Lindberg (Karolinska Institutet) and part-time employee at Molecular Cancer Diagnostics at Karolinska University Hospital commented on the test’s clinical implementation. “It’s great news that this test is now being implemented in clinical routine. It gives more patients with metastatic prostate cancer access to individualized treatment. The ProBio Prostatacancer Assay has been optimized to detect mutations from limited amounts of DNA, which has previously been a challenge for this patient group.”

Clinical routine implementation was done in collaboration with Hannes Olauson and Felix Haglund, molecular pathologists working at Karolinska University Hospital. The ProBio Prostatacancer Assay is based on research previously published in several scientific journals, including Genome Medicine and Clinical Cancer Research.

Progress in precision medicine

As of May 2022, men with metastatic castration-resistant prostate cancer carrying a mutation in either the BRCA1 or BRCA2 genes could be treated with Olaparib. The newly developed analysis can identify these mutations by sequencing cell-free DNA from dying tumor cells enriched from plasma, so-called circulating tumor DNA (ctDNA). ctDNA analysis enables a more current view of the mutations compared to using old leftover diagnostic tissue. However, the most important biomarker, loss of BRCA2, is particularly challenging to detect. Markus Mayrhofer (NBIS, SciLifeLab) recently joined Lindberg’s team and co-developed a new bioinformatic algorithm (Jumble), providing state-of-the-art sensitivity to detect loss of BRCA2. Karolinska University Hospital now offers this analysis, initially developed for the ProBio study (www.probiotrial.org).

ProBio is a prospective clinical trial enrolling patients in Switzerland, Norway, Belgium, and Sweden. Biomaterial is shipped from all four countries to Karolinska Institutet Biobank every week, subsequent processing takes place at Scilifelab, and sequencing is performed at the Clinical Genomics core facility. “Without the infrastructure at SciLifeLab and the excellent sequencing service offered at Clinical Genomics, the ProBio trial and the development of the ProBio Prostatacancer Assay would not have been possible,” Johan explains.

The success of this diagnostic test can be traced back to the decade-long collaboration between Valtteri Wirta’s team at Clinical Genomics, Johan Lindberg’s team at Karolinska Institutet, and the research infrastructure available at SciLifeLab. “This test is a great example of our now 10-year collaboration with Johan’s team and shows the value of linking together excellent research environments, state-of-the-art research infrastructures at SciLifeLab, and clinical diagnostic laboratories within the healthcare sector. By combining the expertise and resources of multiple stakeholders, this test demonstrates the power of synergistic efforts in pushing the boundaries of scientific discovery and clinical applications”, says Valtteri Wirta, Platform Scientific Director at Clinical Genomics.

Future perspectives and research

The team behind the ProBio Prostatacancer Assay is already looking ahead to the next big step and plans to conduct further research to improve efficiency. “Just getting the assay implemented is a big step for precision medicine. However, these assays are not cheap, we need to make sure that the testing is performed in an efficient manner, otherwise, we risk the enthusiasm for precision medicine. This is very important as we plan to implement similar assays for other cancer diagnoses later this year. All cancer patients should have access to the best assays,” says Felix Haglund.

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Contact information

Johan Lindberg, Researcher at SciLifeLab and Karolinska Institutet, johan.lindberg@ki.se

Valtteri Wirta, Platform Scientific Director at Clinical Genomics, valtteri.wirta@ki.se

Felix Haglund, Head of Molecular Cancer Diagnostics, Karolinska University Hospital, felix.haglund@ki.se

Hannes Olauson, Molecular pathologist, Karolinska University Hospital, hannes.olauson@ki.se

Markus Mayrhofer, Bioinformatician at NBIS, SciLifeLab, markus.mayrhofer@scilifelab.se