Sperling Prostate Center

Biomarkers for Inflammation: An Early Warning System

UPDATE: 3/11/2024
Originally published 2/3/2022

The PROCA-life study of inflammation biomarkers (early prostate cancer warning signs) described below drew upon data from 16,879 healthy male participants in a prospective cohort project called the Tromsø Study (1994-2016). Three years later, the PROCA-life team used the same data to analyze a different PCa omen. The authors explored body composition (fat) as a risk factor for PCa incidence and death.

They presented their findings on Oct. 21 to the 2023 Congress of the European Society for Medical Oncology.[i] They found that the rate of PCa diagnoses increased from 1995 to 2019, which parallels a general rise in obesity rates in Western society. Men who were obese (BMI ≥ 30) before PCa diagnosis had higher risk of PCa as well as greater risk of PCa-specific death. They also found that those who had a weight gain >5% over the study’s duration had three times the risk of developing PCa.

Thus, obesity and mid-life weight gain are early warnings of greater PCa risk. This study supports “the importance to combat excess weight gain in the general population,” say the authors.


Question: What lies 66°33’48.2″ north of the equator and around the entire globe?
Answer: It’s the Arctic Circle, and north of that latitude is the North Warning System, a 14-mile wide series of long- and short-range radars that run nearly 3,000 miles east to west, stretching from Canada’s eastern provinces to our own state of Alaska. It was established and is run by the North American Aerospace Defense Command (NORAD), and its purpose is defense. It will give early warning of hostile missiles coming toward our continent from over the north pole so our military repel the attack. The Arctic is thus a very good location for sounding an early warning.

Another country that straddles the Arctic Circle is Norway, home of some very bright scientific minds. When those minds develop a study in collaboration with equally bright U.S. minds from Harvard, University of Washington, and others, we can expect enlightening results.

Chronic inflammation and prostate cancer

Indeed, all those IQ’s were applied to designing and implementing the PROCA-life (Prostate Cancer Throughout Life) study. Although these scientists and clinicians have no connection with the North Warning System, PROCA-life and NORAD share a common mission: early warning. For PROCA-life, it’s all about a simple blood test for levels of two biomarkers that reveal hidden chronic inflammation:

  • High-sensitivity C-reactive protein (hs-CRP)
  • White blood cells (WBC)

You ask, what does inflammation have to do with prostate cancer (PCa)? The short answer is, a LOT! Inflammation always begins as part of the body’s defenses against injury or disease. When that happens, it’s called acute (short-term) inflammation; once the threat is resolved, the inflammation is supposed to recede. However, if it lingers (progresses from an acute to a chronic, prolonged condition), it becomes an enemy called chronic inflammation. There is no doubt that it is implicated in cardiovascular disease, gastro-intestinal disorders, diabetes, neurological diseases, joint problems—and cancer!

This includes prostate cancer. (Read a longer explanation in my blog on prostate inflammation, prostatitis and PCa, or any of my other PCa blogs on inflammation-related topics.) However, chronic inflammation usually has no signs or symptoms that it is silently lurking until a major health problem shows up. That’s why the results of the PROCA-life study are so important.

PROCA-life results

The aim of PROCA-life was to determine if high blood levels of hs-CRP and WBC are associated with increased risk and severity of PCa. The question is, can these two biomarkers act as an early warning of PCa risk? The research team designed a prospective, population-based cohort study, and recruited 7,356 cancer-free men in Tromsø, Norway, a cultural hub north of the (brrrr) Arctic Circle:

Prediagnostic WBC and hs-CRP were assessed from blood collected at study entry; 2,210 participants also had a second CRP measure during follow-up. During a mean 11.8 years follow-up, 509 men developed prostate cancer…[ii]

The investigators were interested in the impact of hs-CRP and WBC together, so they developed a combined systemic inflammatory score (SIS). This resulted in a range of scores from 2-6. The team defined 2-4 as a low SIS score, and 5-6 as a high SIS score.

Statistical analysis showed that high SIS scores produced a 28% increased risk of PCa, with a 68% increased chance of metastatic PCa. Statistically, each 1-point increase in SIS increased PCa risk by 9% and metastatic disease by 25%. Thus, the two biomarkers can indeed act as a red flag, an early way to identify men whose chronic inflammatory scores denote their vulnerability to PCa as well as other diseases. The authors concluded, “Our study supports that hs-CRP including repeated measurements alone or in combination with WBC may be a useful inflammation-related biomarker for prostate cancer risk and prognosis.”

Currently, the prostate specific antigen (PSA) blood test is used to screen men for the presence of PCa, but PSA is of little use as an advance warning. By the time PSA is suspicious for the disease, it’s because the disease is already present. Men who are health-conscious should discuss with their doctors the merits of occasionally testing for inflammatory biomarkers as a barometer of chronic inflammation. Thanks to the PROCA-life study, we now know that high levels of either—but especially both—markers can put a man on notice about his PCa risk. The study’s lead author, Einar Stikbakke, a PhD candidate at The Arctic University of Norway, joins his colleagues in pointing out the advantage of using these WBC and hs-CRP. “Importantly, hs-CRP and WBC are often used in routine clinical practice, and thus easily accessible… Our findings contribute to understanding the relationship between inflammation and prostate cancer development, and may be useful in future research on prostate cancer etiology and possibly prevention.”[iii] Thanks to all those near the Arctic Circle whose early warnings help keep us safe.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] M. Støyten, et al. “Body composition in adult life and prostate cancer (PCa) incidence and mortality: The PROCA life study.” ESMO Congress, presented Oct. 21, 2023. Annals of Oncology (2023) 34 (suppl_2): S954-S1000. 10.1016/annonc/annonc1334.
[ii] Einar Stikbakke, Elin Richardsen, Tore Knutsen, Tom Wilsgaard et al. Inflammatory serum markers and risk and severity of prostate cancer: The PROCA-life study. Int J Cancer. 2020 Jul 1;147(1):84-92.
[iii] Charnow, Jody. “Inflammatory markers predict prostate cancer risk.” Renal & Urology News, Jul. 29, 2020. https://www.renalandurologynews.com/home/news/urology/prostate-cancer/inflammatory-markers-prostate-cancer-risk/


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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