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Why PSA levels alone shouldn’t define your prostate cancer risk

Martina Ambardjieva, MD, PhD
Conditions
July 9, 2025
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“My PSA came back at 6.2 — does that mean I have cancer?”

It’s one of the most common and emotionally charged questions I hear in the clinic. The prostate-specific antigen (PSA) test, once celebrated as a breakthrough in early cancer detection, has become a double-edged sword. For many men, a slightly elevated PSA level is enough to trigger panic — and for some physicians, enough to trigger a biopsy.

But here’s the truth: PSA levels are not a diagnosis. They are just one piece of a much larger clinical picture. And when taken in isolation, without context or nuance, they can lead to unnecessary anxiety, procedures, and even overtreatment.

As urologists, we need to do better, not by abandoning PSA testing, but by rethinking how we use it. Because one number should never define a man’s cancer risk.

What PSA levels actually measure – and don’t

PSA, or prostate-specific antigen, is a protein produced by both normal and cancerous cells in the prostate. A small amount naturally circulates in the bloodstream, and the PSA test measures its concentration.

While an elevated PSA level may raise concern for prostate cancer, it’s important to understand that PSA is not cancer-specific. In fact, many non-cancerous conditions can increase PSA levels, including:

  • Benign prostatic hyperplasia (BPH) — a common, non-cancerous enlargement of the prostate
  • Prostatitis — inflammation or infection of the prostate
  • Recent ejaculation, vigorous exercise, or even a digital rectal exam prior to the blood draw

PSA levels also naturally increase with age and prostate volume, meaning that what’s “elevated” in one patient might be completely normal in another.

This is where confusion often begins, because while the PSA test is sensitive to prostate activity, it isn’t specific enough to tell us why the number is high.

The problem with relying on a single cutoff

For years, a PSA level of 4.0 ng/mL was widely accepted as the threshold for concern. If you were above that line, you were often sent for a biopsy. If you were below it, you were told everything was fine. But real-world data and decades of clinical experience have shown that this binary approach is deeply flawed.

Prostate cancer can and does occur in men with PSA levels under 4.0. At the same time, many men with PSA levels above 4.0 don’t have cancer at all. In fact, large studies have demonstrated that using a single cutoff point can lead to both missed cancers and unnecessary procedures.

The truth is that PSA levels exist on a spectrum. A one-size-fits-all threshold oversimplifies a biologically complex disease, and it risks causing more harm than good.

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That’s why modern urology is shifting away from the rigid cutoff model. Instead of asking “Is it above 4?”, we should be asking “What does this PSA mean in the context of this individual man?”

Overdiagnosis and overtreatment: Real harms from misinterpretation

One of the most significant and often overlooked consequences of misinterpreting PSA levels is overdiagnosis. This refers to the detection of prostate cancers that are so slow-growing or biologically inactive that they would never have caused harm during a man’s lifetime.

But once a man hears the word “cancer,” even if it’s low-risk, it often triggers a chain reaction: biopsy, anxiety, surgery, radiation, and side effects that may never have been necessary. These treatments, while life-saving in the right context, carry real risks, including erectile dysfunction, urinary incontinence, and psychological distress.

This is not a rare occurrence. Studies estimate that a significant percentage of men diagnosed through routine PSA screening undergo unnecessary treatment for cancers that might never have progressed.

The goal is not to ignore prostate cancer; it’s to treat the right cancers in the right patients at the right time. That starts by understanding that an elevated PSA level does not always require immediate action, and sometimes, doing less is doing better.

Smarter ways to use PSA: Context is everything

Instead of reacting to a single PSA level in isolation, clinicians today are encouraged to consider a more comprehensive risk assessment. PSA should be interpreted not as a standalone value, but alongside a variety of patient-specific factors.

Among the most valuable tools we now have are:

  • PSA velocity: how quickly PSA is rising over time
  • PSA density: PSA level relative to prostate volume (often measured via ultrasound or MRI)
  • Free vs. total PSA: lower free PSA percentages may suggest higher cancer risk
  • Risk calculators: online tools that integrate age, family history, ethnicity, digital rectal exam findings, and PSA trends
  • Multiparametric MRI: increasingly used to assess whether biopsy is even necessary

These refinements allow us to risk-stratify patients more accurately, sparing many from invasive procedures while catching clinically significant cancers earlier.

PSA is still a useful test, but only when used thoughtfully, in the context of the whole patient.

Shared decision-making is the future.

Prostate cancer screening has evolved into a far more nuanced conversation than it once was. Rather than relying on a uniform screening model, today’s best practice emphasizes shared decision-making, a thoughtful process that takes into account each patient’s medical profile, values, and preferences.

Risk is not distributed equally. Men with a family history of prostate cancer, those of African descent, or individuals with other predisposing factors may require earlier or more intensive screening. Others, particularly those with limited life expectancy or low-risk profiles, might reasonably opt for less aggressive approaches.

Equally important is understanding what matters most to the patient, whether it’s preserving quality of life, minimizing intervention, or pursuing peace of mind through early detection.

When physicians and patients engage in open, informed discussions about PSA testing and its implications, the result is a decision rooted not just in data, but in clinical relevance and personal meaning. That’s where prostate cancer screening finds its greatest value.

Final thoughts

PSA testing has come a long way since it was first introduced. It has saved lives, but it has also caused confusion, fear, and overtreatment when taken out of context.

We owe it to our patients to move beyond a reflexive response to PSA levels. It’s time to look at the bigger picture: age, risk factors, trends, and values. With better tools, better conversations, and a commitment to nuance, we can make prostate cancer screening smarter, safer, and more meaningful.

The PSA value itself is not the enemy, it’s how we respond to it that makes all the difference.

Martina Ambardjieva is a dedicated urologist and medical educator with extensive experience in both clinical practice and academic instruction. She earned her MD from the University “Sv. Kiril i Metódij” in Skopje and completed her PhD in urological oncology, with a focus on bladder carcinoma. Her scholarly work includes numerous publications in oncologic urology, urinary calculosis, and men’s health.

Dr. Ambardjieva currently serves as a urologist at the PHI University Surgical Clinic “Naum Ohridski” and completed her residency training at the University Urology Clinic in Skopje. Earlier in her career, she practiced as a general medical doctor at Sante Plus General Hospital and completed a medical internship at the University of Ljubljana.

In addition to her clinical responsibilities, Dr. Ambardjieva is a teaching assistant at the Medical Faculty in Skopje. She works additionally as a collaborator for Dr. Telx. She has held leadership positions in the European Medical Students’ Association and actively participates in international medical education and policy. She has attended numerous congresses and workshops in France, Italy, Canada, and Turkey, and serves as a delegate for the European Association of Urology (EAU), contributing to cross-border initiatives in urology. Certified in laparoscopic surgery, she continues to integrate patient care, research, and education in her professional work.

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