Part Three: PSA use for Prostate Cancer Screening

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This is part three of a four-part series on the PSA test in an attempt to demystify the most feared blood marker in men.

 

Part one: What is PSA and what it does

Part two: Benign reason’s why PSA goes up

Part three: PSA use for Prostate Cancer Screening 

Part four: PSA after prostate cancer treatment

 

The Prostate Specific Antigen (PSA) test is the number one used biomarker for prostate cancer screening. In other words, the PSA blood test starts the unpleasant process of biopsies, prostate cancer treatment when malignant cells are found and side effect treatment from the cancer treatment. Many people think PSA is an expensive waste. One of those people is Dr. Richard Ablin, the discoverer of PSA who called this test in a New York Times article, The Great Prostate Mistake. He also wrote the book the Great Prostate Hoax condemning the PSA test for prostate cancer.

Should we stop PSA testing for prostate cancer screening?

No. I will explain. Stay with me.

How does PSA work?

As we learned in the previous article of this series, PSA breaks through the wall of the glandular portion of the tissue and seeps into the bloodstream for many malignant and mostly benign reasons. Ideally, the PSA molecule is only found in the semen. In fact, there are one million times more PSA in the semen than in the blood.

PSA in men before Prostate Cancer diagnosis

The “normal” range of 0.0ng/ml – 4.0ng/ml you see in lab reports is absurd.

Anything under 4ml/ng does not mean you don’t have prostate cancer. In fact, 15% of men with a PSA under 4 develop prostate cancer (Thompson et al. 2004)

Generally speaking, PSA is age-related. For example, a 40-year-old “should” have a PSA well under 1.0ml/ng (exception to the rule, this individual may have an infection of his prostate or other non-cancer causes to his PSA to be above 4).

A 60-year-old with a PSA of 2 may be fine.

A steady trend upward, even if the number is under 4, after three or four PSA tests may be more connected to prostate cancer once prostatitis or other benign conditions are ruled out.

On the previous article, we spoke about non-cancer reasons why PSA is elevated, but there are also numerous reasons why PSA is falsely low, meaning, one can have cancer while there PSA is “low.”

There are two things that cause a false lower PSA:

  1. The meds Finasteride (Proscar) and Dutasteride (Avodart) – falsely lowers PSA up to 50%.

2. Obesity: estrogen activity (which big men have more of) causes a decrease in PSA.

FYI: Obese men typically have worse cases of prostate cancer and higher changes of prostate cancer relapse after treatment. (Cao, 2011) Yet another motive for overweight men to get in shape.

The Good with PSA Screening for Prostate Cancer

Over the past 28 years, since the introduction of prostate-specific antigen (PSA), the incidence of metastatic prostate cancer and dying from this disease has significantly decreased. Although it is hard to connect the cause of prostate cancer decline to PSA, the five-year cancer-specific survival increased from 69% in the 1970s to now more than 95%, associating longer survival in diagnosed men to PSA examination.

 

The United States Preventive Service Task Force (USPSTF) on PSA screening

The United States Preventive Services Task Force (USPSTF) is a group of non-urologists or oncologists; mostly experts in primary care and researchers who collectively review the evidence for what screening tools and treatments are most effective for patients.

The USPSTF has a grading system ranging from grade A, where the task force recommends for a service (screening or treatment) to grade D where the recommendation is against a service, and everything else in between. I stand for insufficient evidence to recommend for or against a service.

In 2011 the United States Preventive Services Task Force (USPSTF) issued a report opposing the use of PSA in screening for prostate cancer and gave a “D” grade recommendation, meaning that existing scientific data demonstrate that there is more harm than good with the use of this test.

Then two years later after further data review, the USPSTF graded PSA screening to a “C,” suggesting that the decision on whether or not to screen for prostate cancer with PSA test should be shared between the physician and patient and it should be used selectively in a case by case basis.

The USPSTF concludes that there is a small overall benefit after a decade with the use of PSA, but continues to note that damages may occur during this screening period. However, there is still a major age-related problem in this current recommendation, because studies have predominantly included patients aged 55-70 years. Thus, the new USPSTF will not recommend PSA for men over 70 years nor for those under 55 years, which seems inadequate, given that it does not take into account clinical characteristics nor individual volition.

The Two Main Studies Driving PSA controversy

The two main humongous trials influencing the USPSTF where the PSA controversy is derived from is The European Prostate Cancer Screening Trial (ERSPC) and The American Prostate Cancer Screening Trial (PLCO) study.

The ERSPC randomized trial of about 160,000 men between 55 and 69 years for PSA screening or control without PSA where the PSA average to indicate a prostate biopsy is ≥ 3.0 ng/ml. The PSA test was taken, on average, only every four years. After monitoring for 11 years, screening reduced the risk of metastases by 41% and the chance of death from prostate cancer by 21%.

More recently, the European ERSPC study, now with almost 14 years of follow-up, confirmed that prostate cancer mortality in PSA screened patients decreased by 32% suggesting that as time goes on and study subjects continued to be followed, there’s benefit from PSA screening.

On the other hand, ERSPC trial continues to show major problem with over diagnosing for prostate cancer screening with PSA of clinically insignificant tumors.

In fact, in the ERSPC study the finding of low-risk tumors (PSA less than10 ng/mL and Gleason score less than 6) was almost three times higher in the screened group than the control group.

The other influential study on prostate cancer screening is the American Lung, Colorectal, and Ovarian Cancer Screening Trial Trial (PLCO) study randomized over 76,000 men aged 55 to 74 years for annual screening with PSA and rectal exam or control group with the “usual urological care,” that is, at the discretion of the urologist.

The PSA value used to indicate biopsy was ≥ 4.0 ng/mL. This study initially showed no mortality benefit for men who received PSA screening in comparison with those who did not.

There is a major problem in the PLCO trial, however.

The “usual care” subjects ( the control group) in the USA includes PSA, in this case almost 90% of the patients in the “usual care” group did the test compared to the randomized group. Therefore, it is no surprise that the rates of prostate cancer death were similar to the screening arm.

This is a multi-million dollar study with a major flaw in it that influence how physicians practice.

That’s freaking insane!

When another group of researchers combined all the major prostate cancer screening studies, they did not find a significant decrease in prostate cancer-specific mortality except in the ERSPC which screening did indeed lower prostate cancer mortality.

They concluded that “Harms associated with PSA-based screening and subsequent diagnostic evaluations are frequent, and moderate in severity. Overdiagnosis and overtreatment are common and are associated with treatment-related harms.”

Other Big Studies on Prostate Screening to Note

Other studies on prostate cancer screening that I find valuable but do not get the attention of PLCO and ERSPC are these two Swedish trials:

In the Gothenburg, in Sweden, 20,000 men were randomized 1:1 for PSA screening every two years or control without PSA. Their average age of participants were 56. The PSA value used to indicate the biopsy was between 3.0 and 4.0 ng/mL. After a 14-year follow-up, there was a relative decrease in prostate cancer mortality of 44%. Prostate cancer was diagnosed in 12.7% of the patients in the screening group and 8.2% of those in the control group.

Again, there was a high rate of overdiagnosis and overtreatment in this trial as well.

Researchers concluded that 293 cases needed to be screened and 12 treated for prostate cancer to prevent one tumor-related death.

[These figures are similar to those for breast cancer screening by the way]

Lastly, this study from Malmo Sweden of over 21,000 patients demonstrated that PSA levels in patients around 45 years of age with no family risk factors could provide data on the chance of developing aggressive prostate cancer and risk of death from the tumor in the coming decades.

When the baseline PSA values were below the population median according to the different age ranges:

  • up to 42 years: ≤ 0.6 ng/mL the chance of death from prostate cancer in 25 years was estimated at 0.1%
  • up to 50 years: ≤ 0.7 ng/mL the chance of death from prostate cancer in 25 years was estimated at 0.5%
  • up to 55 years: ≤ 0.9 ng/mL the chance of death from prostate cancer in 25 years was estimated at 0.8%

These authors suggest that only three PSA measurements, the first performed at around 45 years, the second at the beginning of the fifth decade of life, and the third at 60 years may be sufficient for a safe risk assessment for half of the population.

My Take on the Science of PSA use on Prostate Cancer Screening

There’s no question that the majority of men screened for prostate cancer will not die from it. In other words, there is indeed over-diagnosis and over-treatment of prostate cancer from PSA screening. No one will argue that.

However, many lives have been saved from prostate cancer screening since the beginning of clinical use in the early 1990’s.

If I am the one in the unfavorable percentage of developing aggressive prostate cancer, I want to know as early as possible and do something about it.

The idea of beginning PSA testing at the age of forty as suggested by the Swedish trial is appealing as I have seen many men in their forties with aggressive prostate cancer.

Prostate cancer screening is a case-by-case process. Every case is different, and the approach has to be individualized to the one patient in the office, not only to what researchers conclude as there are design flaws in all studies.

The Dr. Geo’s Guide to Prostate Cancer Screening

Many of my patients, naturally, since I am a holistic practitioner, want to avoid biopsies.

I don’t blame them. I don’t know anyone who gets excited about having their prostate poked 12+ times and have blood come out in their urine and semen for up to two weeks.

When I partner with patients to determine if avoiding a prostate biopsy is the right for them, we look at:

If most of the results from testing indicate suspicious prostate cells, then we look into getting a 3-Tesla MRI.

If the MRI highly suggest aberrant cells, then I would recommend a biopsy, but not a random ultrasound guided one, a targeted MR fusion biopsy.

Additionally, I recommend men to get a PSA reading at forty years of age, regardless of family history and use that as their baseline. If there is no family history and PSA is normal relative to age, do a PSA every five years. If there is a family history (father, brother, etc) then PSA should be taken once a year.

The PSA number is not the problem. What you do with that number is what matters. 

Not all elevated PSA requires a biopsy.

The bottom line is that PSA is decent, though imperfect marker for prostate cancer screening and have saved lives.

At a minimum, an elevated PSA can tell you if something is going on in the prostate, even if it’s not cancer, maybe inflammation or other benign reasons.

The ultimate goal of prostate cancer screening is this:

Find a cost-efficient method of locating tumors that have the most potential to be deadly. Leave tumors that are not deadly alone, or better yet, not find them in the first place. (The “C” word diagnosis, even for indolent tumors prokes anxiety and unnecessary worry). Have a treatment that can remove the potentially deadly tumor without sacrificing quality of life.

Well, maybe one exception, some tests like the MRI are expensive, and health insurances don’t always cover it despite evidence indicating that MRI testing reduces the risk of overdiagnosis.

Yep, that frustrates me too. HERE is what I found to work to get your prostate MRI covered.

The methods of the screening I highlight above are not perfect by themselves but better collectively in providing the best chance of accomplishing the goal of better screening practices to finding and treating deadly prostate cancer.

Last 3 Blog Posts:

[Not part of this series]

ADT, Apalutamide, Exercise in the treatment of prostate cancer

Traditional Chinese Medicine treatment for Erectile Dysfunction

Why I am into Intermittent Fasting 

 

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by Dr. Geo

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