Prostate cancer is a disease with more than 1.3 million new cases each year, where about half of these patients would have been much better off if their cancer had not been diagnosed and treated. In contrast, the other half completely depend on proper treatment to survive. We have little, and no exact, knowledge about what distinguishes an indolent cancer from a lethal one. The incidence of prostate cancer has dramatically increased in the last 40 years, while mortality rates remain mostly unaltered. Unnecessary treatment is a challenge for both patients and healthcare systems, and low-risk patients should be included in active surveillance programs and not treated unless the disease is progressing.
Biomarkers that reliably detect or predict disease progression would be of great societal value and have a strong impact on these patients’ health and quality of life.
Since 2013, our institute has closely collaborated with Vestfold Hospital Trust (VHT) and their active surveillance (AS) program for patients with low- and intermediate-risk prostate cancer. We have been collecting material and follow-up data from this cohort of patients and will continue to do so at least throughout the period of 2021-2024.
Our current results indicate that DNA ploidy and Phosphatase and Tensin homolog (PTEN) status may improve decision making in AS. This study has so far been performed for 235 patients enrolled in the program between 2005 and 2014. So far, A total of 1469 tumour biopsies from all diagnostic and surveillance procedures have been analysed in an attempt to control for intratumor heterogeneity and limited sampling of the tumour. We found that DNA ploidy and PTEN status were associated with disease reclassification and treatment, both as individual biomarkers and as a combined biomarker. The highest prognostic value was observed for patients with both non-diploid tumour and PTEN loss. Importantly, in almost half of the patients, these indicators of poor prognosis could have been detected prior to disease reclassification, according to our AS protocol. Markers of these alterations could serve as additional independent parameters to help identify patients with aggressive disease at an earlier stage. Currently, we are expanding this study to include approximately 100 additional patients enrolled in AS in 2015-2016.
We will study other biomarkers described herein that may differentiate indolent from aggressive disease, particularly in patients with intermediate-risk features. First, we will test the biomarkers that can be applied to standard HE tissue sections, such as Mitotic Index, Stroma fraction and Histotyping. Second, using our sequential staining protocol, we can assay six to ten additional molecular biomarkers. The markers will be selected among the candidate genes described later.
Provided positive results from Nucleotyping, this marker will also be assessed in the AS cohort. Milestones for the different markers are found under the respective projects.
This text was last modified: 18.08.2021