Despite prostate cancer being one of the most common causes of cancer in men, prostate cancer screening with the prostate-specific antigen (PSA) blood test remains a hot topic of debate.
The PSA blood test is a biomarker that detects abnormalities of the prostate, from enlargement (BPH) to inflammation (prostatitis) to prostate cancer. Most labs reference "normal" PSA levels of 0-4.0 ng/mL; however, PSA levels tend to increase with age.
According to Johns Hopkins Medicine:
For men in their 40s and 50s: A PSA score greater than 2.5 ng/ml is considered abnormal. The median PSA for this age range is 0.6 to 0.7 ng/ml.
For men in their 60s: A PSA score greater than 4.0 ng/ml is considered abnormal. The normal range is between 1.0 and 1.5 ng/ml.
An abnormal rise: A PSA score may also be considered abnormal if it rises a certain amount in a single year. For example, if your score increases more than 0.35 ng/ml in a single year, your doctor may recommend further testing.
Why PSA Screening Remains Controversial
To make things even more complicated, one study found that 15.2 percent of men with a PSA 4.0 ng/mL or less had biopsy-proven prostate cancer. The vast majority of these had a Gleason score of 6, though 2.3 percent in this range had a Gleason score of 7 or higher.
Another study examined the prevalence of undiagnosed prostate cancer through a review of 19 autopsy studies encompassing over 6,000 men. It showed a high prevalence of asymptomatic and undiagnosed prostate cancer, even in men as young as 30, with prevalence increasing with age.
Among men aged 70-79, 36% of Caucasians and 51% of African Americans had previously undetected prostate cancer.
So, at this point, you are starting to see the incredible diversity and complexity associated with prostate cancer and PSA screening.
Balancing Early Detection with Overdiagnosis
While PSA screening has the potential for early detection and can reduce prostate cancer deaths in some men, it carries a high risk of causing overscreening, overdiagnosis, and overtreatment.
That's because PSA screening detects a high proportion of men with prostate cancer that grows slowly and rarely, if ever, metastasizes.
Overscreening causes unnecessary, risky prostate biopsies. Overdiagnosis results in overtreating indolent cancers that would never cause harm.
This overtreatment includes radical prostatectomy and radiation, resulting in life-altering complications of urinary incontinence, erectile dysfunction, and bowel dysfunction.
Thankfully, as the adoption of active surveillance of prostate cancer has increased, doctors and patients are much less likely to overtreat insignificant cancers. But in the past, this wasn't the case, and overtreatment was common.
Even choosing active surveillance comes with its own anxieties, with repeat biopsies carrying risks including bleeding and, rarely, urosepsis. And God forbid a man with an insignificant cancer gets treated with androgen deprivation therapy, but it has happened.
A substantial percentage, estimated to be between 23% and 60%, of prostate cancers detected through prostate-specific antigen (PSA) screening are considered indolent.
The reason for the wide range is that different studies included men of varying ages, races, and nationalities, as well as different diagnostic criteria.
But for those men with early PSA detection of clinically significant prostate cancer, it can be a lifesaver.
From the 'PSA Boom' to the 2012 Bust
In 1986, the United States (U.S.) Food and Drug Administration (FDA) approved the use of a serum PSA test for monitoring response to prostate cancer therapy and relapse.
PSA-based prostate cancer screening began in 1991 after studies showed PSA testing helped find localized prostate cancer. Its use in screening progressively increased, and in 1994, the FDA approved it as a screening test.
PSA-based prostate cancer screening took off, and healthcare providers using it as a screening tool in the early days were unaware of all the nuances and hazards later shown by the studies mentioned above.
After reviewing the data in clinical trials and seeing the harm of overdiagnosis and overtreatment caused by PSA-based prostate cancer screening, the U.S. Preventive Services Task Force (USPSTF) called a halt to routine PSA-based screening in 2012 with a landmark "D" rating.
The expert panel concluded that screening caused more harm than the small number of lives it might save. This significant policy change upset urologists, who believed the panel had dismissed the value of catching cancer early and saving lives.
What happened next was troubling but not surprising. Doctors began seeing more aggressive, advanced prostate cancers that had spread beyond the prostate. It appeared the drop in screening was causing cancers to be caught too late.
Shared Decision-Making (SDM): A Modern Imperative
In response to this new evidence, the USPSTF revised its recommendation in 2018, stating that men aged 55 to 69 should make individual screening decisions after consulting with their doctors about both the potential benefits and risks.
They acknowledged that the right choice depends on each man's specific situation and values and that screening isn't right or wrong for everyone.
Instead, it requires honest conversations between patients and doctors about what matters most to each individual.
The American Urological Association (AUA) had already adopted shared decision-making into its prostate cancer screening guidelines in 2013, and now the USPSTF was coming on board, followed shortly by the National Comprehensive Cancer Network (NCCN).
As a direct consequence of decades of conflicting evidence, shared decision-making has become a key component of responsible screening. However, this change in their guidelines has placed an enormous responsibility on doctors and other healthcare professionals.
However, SDM is crucial for an issue like PSA-based prostate cancer screening to help balance some of the uncertainty and potential harms.
Shared decision-making occurs when doctors and patients collaborate to determine the best healthcare options. It's not just the doctor telling the patient what to do or the patient making decisions alone without medical input.
Instead, both people bring something meaningful to the table.
The doctor brings their medical training, experience with similar cases, and knowledge of what the research has shown to work. The patient brings their life situation, what matters most to them, their fears and hopes, and their personal health goals.
When you combine these, you get decisions that are both medically sound and personally meaningful.
What makes this approach special is that it recognizes there's usually more than one reasonable path forward. Sometimes, the "right" choice for one person may be entirely wrong for another, even if they have the same medical condition.
That's because each person's life circumstances, values, and priorities are different.
If the clinician and patient choose to skip a treatment or avoid a screening test, they're not giving up or being careless. Instead, they're being thoughtful about what truly serves the patient best.
Every medical intervention carries risks, side effects, or burdens that might outweigh the benefits for a particular person's situation.
This approach requires doctors to really understand their patients as whole people – their values, fears, goals, and what makes life meaningful to them. It's about practicing medicine with both scientific knowledge and deep human wisdom, recognizing that the "right" choice isn't always the most aggressive one.
Sometimes, the most compassionate thing clinicians can do is step back and allow the person's own healing capacity and life choices to guide the decision. Doing this honors what matters most to each patient and recognizing that good medical care sometimes means choosing restraint over action.
The goal is to ensure that patients understand their options clearly and feel confident that their final decision reflects both sound medical judgment and their values and circumstances.
SDM is more than just a doctor providing you with information, and then you make a decision. A robust SDM protocol is a well-informed collaboration between the healthcare provider and you.
And it's especially useful when the outcomes aren't clear-cut or when weighing the benefits and risks involves some really subjective judgment calls.
This collaboration intends to come up with a quality decision based on these components:
Information from the healthcare provider in the form of facts, including risks versus benefits.
All the viable paths or alternatives you could take.
Your personal preferences and values - what matters most when considering the risks, side effects, and quality of life.
Doctors are usually good at providing hard facts and alternatives. However, understanding patient preferences is more complicated because it requires a fundamental shift in thought.
Doctors must listen to you and move from just delivering information to diagnosing preferences, actually understanding what makes you tick.
It's about the doctor fully understanding your priorities. And they can only accurately understand your priorities if they present the correct facts and ask the right questions.
A Four-Step SDM Blueprint in Practice
Here's an example of a 4-step SDM discussion:
Potential Benefits of PSA Screening:
Mortality Reduction: For men aged 55-69, screening about 1,000 men over ~13 years may prevent approximately 1.35 deaths from prostate cancer.
Prevention of Metastatic Disease: Screening may prevent approximately 3 out of 1,000 men from developing metastatic prostate cancer.
Psychological Reassurance: For some men, knowing their cancer status can provide peace of mind and a sense of control.
Potential Harms of PSA Screening:
False-Positive Results: A positive PSA test may not indicate cancer and can lead to anxiety, additional tests, and potentially unnecessary biopsies.
Biopsy Complications: Prostate biopsies, while rarely serious (e.g., urosepsis in 0.5%), can cause discomfort, bleeding, or rectal hemorrhage in about half of men.
Overdiagnosis: This is a major concern, as screening can detect "indolent cancers" that would never have caused symptoms or shortened a man's life. Estimates suggest overdiagnosis may occur in 20%-50% of screen-detected cancers.
Overtreatment: Overdiagnosis often leads to overtreatment with surgery or radiation, resulting in unnecessary exposure to side effects.
Treatment Complications: Radical prostatectomy or radiation can cause long-term side effects such as urinary incontinence, erectile dysfunction, and bowel problems, negatively impacting quality of life.
Psychological Harms: The "labeling" of a cancer diagnosis, even for low-risk disease, can cause anxiety, depression, and uncertainty, irrespective of treatment.
Mitigating Harms with Active Surveillance (AS):
For men diagnosed with low-risk prostate cancer, AS is a recommended and increasingly accepted option. It involves monitoring the cancer with regular tests and interventions only if progression occurs, allowing men to avoid or delay invasive treatment and its side effects.
The second step involves eliciting a patient's values regarding prostate cancer screening, active surveillance, and treatment.
The clinician presents the patient with a list of competing values that are central to the screening decision. For example:
Maximizing Lifespan: "My top priority is to do everything possible to live as long as possible, even if it involves risks or side effects."
Maintaining Current Quality of Life: "My top priority is to preserve my current lifestyle, including sexual and urinary function, and avoid medical interventions unless absolutely necessary."
Achieving Peace of Mind: "My top priority is to reduce uncertainty and anxiety. I want to know for sure if I have cancer."
Avoiding Medical Procedures: "My top priority is to avoid invasive tests like biopsies and treatments like surgery."
The patient ranks or prioritizes these statements, providing the clinician with a concrete, patient-generated framework to guide the rest of the conversation.
The third step moves the conversation from generic statistics to personalized risk information.
Clinicians might use a validated, interactive risk calculator, such as the Prostate Cancer Prevention Trial (PCPT) Risk Calculator 2.0, which incorporates multiple variables to generate a more precise risk profile.
During the visit, the clinician inputs the patient's data, including their age, race, family history, PSA level, and digital rectal exam (DRE) findings, into the tool. This calculator provides a preliminary assessment of the risk of prostate cancer if a clinician performs a prostate biopsy.
This step transforms the talk into a review of the patient's situation, making the risks real and relatable.
The fourth step completes the decision-making process by bringing together everything the clinician and patient have learned about the patient's personal risk and what matters most to them.
Here, the clinician shifts into the role of a decision coach rather than simply telling the patient what to do. It's the clinician's job to help connect the dots between the patient's risk numbers and their priorities.
The conversation may become very direct and personal:
"Mr. Smith, you told me that maintaining your current quality of life is what matters most to you right now. When we look at your specific risk calculator results, your chance of having a high-grade, aggressive cancer is quite low, around 5%. Since your main goal is to avoid treatment side effects, and your risk of dangerous cancer is relatively small, it makes sense that skipping the biopsy and simply rechecking your PSA in two years would best match what you've shared with me about your priorities. How does that feel to you?"
This method ensures that whatever they decide isn't something the clinician is imposing on the patient but rather a natural conclusion that flows from their values combined with their medical data.
The patient drives the decision. The clinician is just helping them see how their priorities and their numbers fit together logically.
Once they reach an agreement, the clinician documents both the plan chosen (such as "Patient will defer screening and return for PSA recheck in 1 year") and the key patient values that led to this decision (such as "prioritizing quality of life preservation").
This process creates a clear record of not only what they decided but also why they chose it, based on what matters most to this particular patient.
Beyond PSA: MRI, Biomarkers, and Genetics
I presented a fairly simplified example of SDM, as there are many more variables to consider in a modern practice. Such as:
The results of any multiparametric magnetic resonance (mpMRI) study, including the PI-RADS score and PSA density.
The results of any liquid biomarker testing, such as 4kScore, percent-free PSA, or SelectMDx.
The results of any germline genetic testing.
Decision Aids: The Missing Ingredient
All of this information is too much to discuss in a 15-minute time slot with patients who inevitably have other medical conditions to address.
The optimal approach is to provide decision aids in the form of brochures or online material to read and/or watch before attending their appointment.
Unfortunately, these preappointment decision aids are not very prevalent.
The Future: Personalised, Data-Driven, Human-Centered
Nevertheless, the days of blanket screening recommendations for every man are behind us. The future of prostate cancer detection needs to be deeply personal, combining cutting-edge technology with meaningful conversations between doctors and patients.
Better tools will sharpen the data, but the final call should rest on what matters most to the patient. Bringing that level of personalization into everyday practice isn’t simple, yet it’s precisely the kind of challenge that can move the field forward.
Until the next newsletter, stay healthy.
Much love,
Keith
Very interesting to read and really helpful keep up the great work many thanks.
I appreciate your balanced and thoughtful analysis of all the pros and cons of PSA screening. I was Gleason 7, in only 2 of 12 cores, from my biopsy. I still opted for surgery because it was the right thing for me. At 67, I believed then (and still do) that having the cancer (along with the prostate) removed would give me the greatest peace of mind. And it has, by far. My follow-up PSA tests have been undetectable. A good friend (age 50) had his prostatectomy about 6 weeks before mine - he was Gleason 9 - and his doctor found a spot on his pelvic bone that has now been treated with radiation. There are no easy answers - and everyone is different!