Is a Prostate Biopsy Always Necessary? What a New Imaging Method Tells Us

"Your PSA is slightly raised and there is an unclear appearance on the MRI. We may need to perform a biopsy." For many men, the days that follow hearing that sentence are among the most anxious of their lives. My patients generally ask two questions: "Do I have cancer?" and "Is this biopsy really necessary?"

Until now, the answer we could give to the second question was usually "yes, to be sure". However, a large newly published study shows that in some patients this answer may change. In this article I want to describe the PRIMARY2 trial - which may be an important turning point in the diagnosis of prostate cancer - without hiding behind medical terminology.

KEY FINDINGS

• One in two patients avoided biopsy: Approximately half of the patients who underwent the new imaging method were not biopsied at all.
• Dangerous cancers were not missed: The success in detecting serious cancers requiring treatment remained at the same level as with the classical method.
• Unnecessary cancer diagnoses fell by more than half: The rate of diagnosing "silent" cancers that would never have harmed the person fell from 32% to 14%.
• The method is reproducible: Different specialists interpreted the same images in largely the same way.

First, Let Us Understand the Problem: Why Is "Unnecessary Diagnosis" a Problem?

It is natural to think that a cancer diagnosis is always a good thing. Early diagnosis saves lives - that is true. But in prostate cancer the situation is a little different.

Some prostate cancers grow very slowly. So slowly that even when a man reaches the age of 80, that cancer may have caused him no symptoms and may not have shortened his life in any way. In the medical literature such cancers are called "clinically insignificant".

So where is the problem? The problem lies in the word "cancer" itself. The life of a person receiving this diagnosis changes: regular check-ups, repeated biopsies, insurance processes, the family's anxiety and, most importantly, the thought that comes to mind every morning on waking. Some patients cannot cope with that anxiety and request an operation or radiotherapy they never actually needed. Those treatments can have permanent consequences such as urinary incontinence and loss of sexual function.

In short, we face this dilemma: we absolutely do not want to miss dangerous cancers; but nor do we want to find harmless cancers unnecessarily and cast a shadow over a person's life. A good diagnostic method is one that can achieve both goals at the same time. That is precisely where the importance of the PRIMARY2 trial comes from.

How Does Today's Pathway Work?

The zone of uncertainty: PI-RADS 2 and 3

If the MRI report says PI-RADS 4 or 5, the path is clear: biopsy is needed. If it is PI-RADS 1, we can comfortably wait. The real difficulty lies with the patients in between:

• PI-RADS 3: "I am undecided." The MRI can say neither that cancer is present nor that it is absent.
• PI-RADS 2 plus high risk: The MRI sees nothing suspicious, but the patient's PSA value or a strong family history is a cause for concern.

In these two groups the physician is squeezed between three options: not performing a biopsy (the risk of missing a cancer), performing a biopsy (the burden of the procedure and the risk of unnecessary diagnosis), or waiting (prolonging uncertainty and anxiety). None is satisfactory.

The New Method: What Is PSMA PET/CT?

Prostate cancer cells carry a "marker" called PSMA on their surface, and this marker becomes more prominent the more aggressive the cancer is. In a PSMA PET/CT scan, a very low dose of a substance that binds to this marker is given intravenously; in the images then acquired, cancer cells literally light up.

In other words, while MRI shows us whether the shape is abnormal, PSMA PET/CT shows the behaviour of the cell. The two answer different questions - and for that reason they can complement one another. PSMA PET/CT has been in use for years; but until now it has mostly been used in patients already diagnosed, to see whether the disease has spread. The question PRIMARY2 asked was new: can this scan be used at the diagnostic stage to guide the biopsy decision?

How Was the Research Conducted?

At seven hospitals in Australia, 660 men who had never had a biopsy took part in the study. All of their MRI results were in the "zone of uncertainty". Participants were randomly divided into two groups by computer:

• First group (331 men): A PSMA PET/CT was performed first. If the scan was clear, no biopsy was performed; if a suspicious area lit up, a targeted biopsy was taken directly from that point.
• Second group (329 men): The standard method was applied - everyone was biopsied.

This design is a randomized controlled trial, the method with the highest evidential value in medicine; the results therefore cannot be explained by chance or by patient selection.

Key Results

Avoiding biopsy. In 163 of the 331 patients undergoing PSMA PET/CT the scan was clear and no biopsy was performed at all. In other words, one in two patients was spared anaesthesia, the needle, the risk of bleeding and the anxiety of waiting for a result.

Serious cancers were not missed. This was the trial's most critical question. Cancers of a nature requiring treatment were found in 12% in the PSMA PET/CT group and 16% in the standard group; the difference was not statistically significant. The detection rate of the most aggressive cancer types was almost exactly the same in the two groups.

Unnecessary diagnosis fell by more than half. Roughly 18 in every 100 patients were protected from a diagnosis that would have cast a shadow over their lives while providing them no benefit.

In medicine, most new methods gain one thing while losing another - if you perform fewer procedures you usually miss something. The striking aspect of PRIMARY2 is that this trade-off did not occur.

So What Does This Mean For Me?

What applies today

• This study was conducted only in a particular patient group: men who had never had a biopsy, with a PSA below 20 and an equivocal MRI result.
• For patients with a clearly suspicious area on MRI (PI-RADS 4-5) the diagnostic pathway has not changed; biopsy is still necessary.
• Patients who have previously had a biopsy, are on active surveillance or already have a diagnosis fall outside the scope of this study.

What is not yet resolved

• Access and cost: PSMA PET/CT requires nuclear medicine infrastructure and is expensive compared with biopsy; reimbursement coverage varies from country to country.
• Long-term follow-up: Data showing how patients who did not undergo biopsy fare over the years are not yet mature.
• Guidelines: International urology guidelines have not yet made this approach a standard recommendation.

For this reason the right approach today is this: PSMA PET/CT is an option that may be considered in selected patients facing uncertainty, at experienced centres and in discussion with the physician - not a new standard to be applied to everyone.

Frequently Asked Questions

Is a prostate biopsy very painful?

Today a biopsy is usually completed within a few minutes under sedation or local anaesthesia. Most patients tolerate the procedure. Even so, blood in the urine or semen for a few days afterwards, mild pain and, rarely, infection can occur. It is not "unbearable"; but if it is unnecessary, it is best not performed.

My PSA came back high, do I have cancer?

No, not necessarily. The most frequent causes of a raised PSA are benign prostate enlargement and prostate inflammation. PSA is only a signal meaning "let us look a little more closely"; it does not make a diagnosis on its own.

My MRI says PI-RADS 3. What should I do?

This means "equivocal", and the decision is made by looking at the whole picture rather than a single number: your PSA value and its trend, your PSA density, your prostate volume, your examination findings, your family history and your age are assessed together. This group is exactly the patient group the PRIMARY2 trial targeted.

Can I request a PSMA PET/CT directly?

This scan is only meaningful if there is an appropriate indication. Applying it to everyone is neither medically correct nor economically sustainable; your urologist needs to assess whether you fall within this group.

Does the scan involve radiation?

Yes, PET/CT involves a low level of radiation. However, the dose used is within the limits accepted in medical imaging, and the expected benefit of the scan outweighs this risk. This assessment is made individually for each patient.

Glossary

• PSA: A protein produced by prostate tissue and measurable in the blood; a raised level can be due to many causes other than cancer.
• PI-RADS: The scoring of a prostate MRI from 1 to 5. 1-2 low suspicion, 3 equivocal, 4-5 high suspicion.
• Biopsy: Taking a tissue sample from the prostate with a fine needle; a definitive diagnosis is made only by examining these samples under the microscope.
• PSMA: A marker molecule on the surface of prostate cancer cells, more prominent in aggressive cancers.
• PET/CT: An imaging method showing where a labelled substance given to the body accumulates; it shows the behaviour of cells rather than their structure.
• Clinically insignificant cancer: A slow-growing cancer that, although present, is not expected to affect a person's lifespan or quality of life.

A Final Word

Prostate cancer is a disease with extremely encouraging outcomes when addressed at the right time and in the right way. But there is an important lesson medicine has learned in recent years: the real goal should be not to find every cancer but to find the one we need to find.

The PRIMARY2 trial is a meaningful step in that direction. As technology advances, the situations in which we can tell our patients "the imaging gives us a clear enough answer" rather than "let us do a biopsy to be sure" will increase.

If you are experiencing this uncertainty right now, I would like you to know that it is a process that can be managed with patience and the right information. I recommend having an open discussion with your urologist, writing down your questions and taking them with you, and making the decision together.

References

• Emmett L, Buteau J, et al. Effect of [68Ga]Ga-PSMA-11 PET-CT in the diagnosis of prostate cancer in men with equivocal or clinically high-risk non-suspicious findings on multiparametric MRI (PRIMARY2): a multicentre, non-inferiority, phase 3, randomised controlled trial. The Lancet Oncology, 10 June 2026.
• The ASCO Post. PSMA PET/CT Scan Reduces Need for Prostate Cancer Biopsies by 50%. 18 March 2026.
• Urology Times. PRIMARY2: PSMA-PET/CT can safely reduce prostate biopsies in men with equivocal MRI.
• UroToday. EAU 2026 Congress - PRIMARY2 presentation.