New Methods Uncover Aggressive Prostate Cancer

Norwegian University of Science and Technology

The research lays a foundation for the possibility that aggressive prostate cancer can probably be detected through a few drops of semen or blood in the long term.

Prostate cancer is the most common form of cancer among men in Western countries.

Studies have detected cancer of the prostate in half of men over 60 years of age , and in about 70 percent of men over 80 years of age.

This shows that the disease is naturally linked to ageing.

"Prostate cancer often develops very slowly. For the vast majority, this is a disease that you live well with, without the need for treatment, but some get an aggressive variant with recurrence of cancer even after surgery. The disease behaves very differently from patient to patient. Understanding what makes the cancer aggressive is crucial for better diagnostics and treatment," says May-Britt Tessem, professor at the Norwegian University of Science and Technology (NTNU).

She believes that existing methods aren't good enough for detecting who gets a mild variant rather than those who get the aggressive type.

Aggressive cancer has its own genetic signature

Now, a research team from NTNU, led by Tessem, has recently published an article in the highly acclaimed journal Nature Communications.

They are the first in the world to combine extremely advanced research methods to detect aggressive prostate cancer.

In a large study, the researchers analysed prostate tissue using advanced methods that combine genetic data, metabolic analyses and detailed tissue images. The aim was to find new characteristics that can predict which patients will develop aggressive disease.

They succeeded.

The results show two important findings.

Aggressive cancer has its own gene expression: The researchers identified a pattern in the gene expression of the tumor itself in prostate tissue in patients with a high risk of recurrence and spread. This signature can become a new tool for distinguishing between patients who need intensive care and those who can manage with less intensive follow-up.

Inflammation of apparently healthy tissue: Signs of inflammation and changes in metabolic processes were also found in the normal tissue close to the cancerous tumour. These glands had high activity of neurotransmitters that attract immune cells, and an increased occurrence of a cell type that can trigger inflammatory reactions. At the same time, the levels of important substances had decreased, suggesting that the gland had lost its normal function.

"Aggressive prostate cancer appears to be associated with inflammation in the area around the cancer cells, combined with specific genetic signatures and metabolic changes in the prostate tissue. This knowledge can provide better methods for early identification of patients at high risk," says Tessem.

Cancer returns after surgery in 30 per cent of patients

Prostate cancer progresses slowly, which means that research on this disease can be slow.

"It takes an average of nine years from surgery to a relapse. About 30 per cent have a recurrence of cancer after surgical removal of the cancer. What we have done is to use samples from some patients who relapsed, and who we can thus define as having an aggressive disease, and compared these with samples from those who did not relapse and who didn't have aggressive disease. The actual samples from the patients were taken about ten to fifteen years ago. As a researcher, it is important to be persistent," says Tessem.

The samples were taken in Trondheim, and controlled in patient cohorts of more than 2000 patients.

Today, prostate cancer is detected through a rectal examination by the doctor, and a blood test called PSA . Since it has become more common for men to take this blood test, the number of new cases of prostate cancer has risen sharply. Now the number of new cases in Norway is about 5200 each year.

When more people are tested for a disease that naturally occurs as part of ageing, doctors have to take next medical step after the blood test, so they get a better clinical picture of the severity.

Today, this involves taking an MRI that provides a detailed picture of the prostate cancer gland and surrounding tissues.

Will lower the threshold for easy screening

Researcher Sebastian Krossa at NTNU has been central to the research. He says it is a well-known problem that many men ignore illness, and that the threshold for a rectal examination is high.

"The PSA test taken with a blood sample today is a correct and important step in lowering this threshold. Nevertheless, it is unfortunately still resource-intensive to determine which patients need intensive followup. The goal of our research is to lay the foundation for it to be possible to easily screen who has aggressive cancer, for example through blood or sperm samples," says Krossa.

Tessem emphasizes that preventing overtreatment is just as important a goal as uncovering those who really need treatment,

"We know that prostate treatment can greatly reduce the quality of life with significant side effects for many patients, such as incontinence, erectile dysfunction and depression. Some patients need intensive treatment of the disease, but this is not always necessary. Many people are overtreated and suffer unnecessary discomfort as a result," says Tessem.

Basic research, not ready for the doctor's office

May-Britt Tessem and her team work with basic research, meaning they study ofvery basic and fundamental processes in the human body. This research has uncovered completely new cancer-related characteristics and correlations.

The new findings are an important piece of a larger puzzle that may result in new and more practical breakthroughs in the future. Basic research is the most important source of major breakthroughs in medical treatment.

Tessem and her team used spatially resolved multi-omics technologies with a combination of transcriptomics, metabolomics and histopathology to map the tumor microenvironment in patients with aggressive prostate cancer.

Multi-omics technologies make it possible to get a three-dimensional view of the tissue and what it consists of. Tessem was awarded a prestigious European Research (ERC) Starting Grant for her research on prostate cancer.

Source:

Krossa, S., Andersen, M.K., Sandholm, E.M. et al. Spatial multi-omics identifies aggressive prostate cancer signatures highlighting pro-inflammatory chemokine activity in the tumor microenvironment. Nat Commun 16, 10160 (2025). https://doi.org/10.1038/s41467-025-65161-

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