Abstract: PD40-06
Sources of Funding: The work was supported in parts by grants from the Finnish Funding Agency for Technology and Innovation Finland Distinguished Professor program, the Academy of Finland, the Cancer Society of Finland, the Sigrid Juselius Foundation, the Medical Research Fund of Tampere University Hospital, National Cancer Institute [R01CA160816, R01 CA175491, P50-CA92629, and P30-CA008748], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, and the Swedish Cancer Society (project no. 14-0722). _x000D_ The Finnish screening trial was supported by grants from the Academy of Finland (grant #260931), Cancer Society of Finland and Competitive Research Funding (Pirkanmaa Hospital District)._x000D_

Introduction

A panel of four kallikrein markers (total, free and intact prostate-specific antigen (PSA), human kallikrein-related peptidase 2 (hK2)) improves predictive accuracy for Gleason score 7 or higher (high-grade) prostate cancer among men biopsied for elevated PSA. A four kallikrein panel model was originally developed and validated on the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as the 4Kscore^tm. We assessed whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC). Additionally, we assessed whether beta-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value.

Methods

Among 4861 biopsied screening-positive participants in the first three screening rounds of the FinRSPC, a case-control subset was selected which included 1632 biopsy positive cases individually matched based on age at biopsy to biopsy negative controls Markers were measured in serum or plasma collected before biopsy. Predictive accuracy of pre-specified prediction models were compared with biopsy outcome.

Results

Our main analysis included men with PSA 4.0-25 ng/mL, 1111 of whom had prostate cancer, 318 with high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve (AUC) of 0.648 (95% CI 0.614, 0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717, 0.774). Adding MSP to the four kallikrein panel led to a statistically significant (Wald test; p=0.015) but small additional increase (0.003) in discrimination.

Conclusions

Four kallikrein markers and MSP in blood improve discrimination of high-grade cancer from Gleason grade 6 cancer or no evidence of cancer at biopsy in men with elevated PSA. These findings provide further evidence that kallikrein markers can be used to inform biopsy decision making. Further studies are needed to define the role of MSP.

Funding

The work was supported in parts by grants from the Finnish Funding Agency for Technology and Innovation Finland Distinguished Professor program, the Academy of Finland, the Cancer Society of Finland, the Sigrid Juselius Foundation, the Medical Research Fund of Tampere University Hospital, National Cancer Institute [R01CA160816, R01 CA175491, P50-CA92629, and P30-CA008748], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, and the Swedish Cancer Society (project no. 14-0722). _x000D_ The Finnish screening trial was supported by grants from the Academy of Finland (grant #260931), Cancer Society of Finland and Competitive Research Funding (Pirkanmaa Hospital District)._x000D_