We investigated whether adding 4Kscore as a reflex test to prostate-specific antigen (PSA) could improve the screening algorithm for prostate cancer (PC).
In the GÖTEBORG-2 PC screening trial, 38 000men (50-60 yr) were invited to PSA testing and, if elevated, followed by magnetic resonance imaging (MRI). For 571 men with PSA ≥3.0 ng/ml and evaluable outcomes, 4Kscore was calculated. The performance using a prespecified 4Kscore cutoff of 7.5% was evaluated.
The area under the curve for 4Kscore to identify intermediate- and high-risk PC was 0.84 (95% confidence interval 0.79-0.89), and the positive predictive value, and negative predictive value were 15% (0.12-0.20) and 99% (97-100%), respectively. Of the 54 men diagnosed with intermediate- or high-grade PC, two had a 4Kscore cutoff below 7.5%, both with organ-confined intermediate-risk PC. Per 1000 men with elevated PSA, adding 4Kscore would have resulted in avoidance of MRI for 408 (41%) men, biopsies for 95 (28% reduction) men, and diagnosis of 23 low-grade cancers (23% reduction) while delaying the diagnosis of four men with intermediate-grade cancers (4%).
Including 4Kscore as a reflex test for men with elevated PSA reduces the need for MRI and biopsy markedly, and results in less overdiagnosis of low-grade PC at the cost of delaying the diagnosis of intermediate-grade PC in a few men. These results add further evidence for including new blood-based biomarkers in addition to PSA to improve the harm and benefit ratio of PC screening and reduce the need for resource-demanding MRI and biopsies.
In this study, 4Kscore, a blood-based biomarker, as a reflex test for men with elevated prostate-specific antigen (PSA), reduces the need for magnetic resonance imaging and biopsy. These results support the inclusion of new blood-based biomarkers in addition to PSA.
European urology. 2024 May 20 [Epub ahead of print]
Andreas Josefsson, Marianne Månsson, Kimia Kohestani, Vasiliki Spyratou, Jonas Wallström, Mikael Hellström, Hans Lilja, Andrew Vickers, Sigrid V Carlsson, Rebecka Godtman, Jonas Hugosson
Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden; Department of Urology and Andrology, Institute of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden. Electronic address: ., Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden., Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Translational Medicine, Lund University, Malmö, Sweden., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Translational Medicine, Division of Urological Cancers, Medical Faculty, Lund University, Skåne University Hospital, Malmö, Sweden.