The prostate cancer screening pendulum just swung… again. One of the most vexing problems in outpatient medicine has been prostate cancer screening: who should be screened and when should they be screened? New developments are finally giving us some clarity. We have a highly effective screening test in the prostate specific antigen test (PSA). This simple blood test is inexpensive and widely available. Finding an elevated PSA can result in detecting prostate cancer at an early, curable stage. But sometimes, the PSA can be too good.
Every year, our hospital holds an annual Community Day where physicians and hospital staff volunteer their time to provide free health information and screening tests to the public. Many of the community members attending are uninsured and low income so Community Day is their only source of screening for chronic diseases and cancers. A few years ago, the hospital agreed to perform free PSA tests and I asked two doctors to staff a prostate cancer screening station. One doctor said “If attendees don’t get PSA tests, I’m not going to participate” and the other doctor said “If attendees do get PSA tests, I’m not going to participate“. So which doctor was right? This is a question that as a 64-year-old man I’ve thought about a lot and it turns out that that both of them were right and both of them were wrong.
The history of PSA screening
Prostate cancer is the most second most common cancer in men (after skin cancer) and the second most common cause of cancer death in men (after lung cancer). It is estimated that 288,300 American men will be diagnosed with prostate cancer and 34,700 American men will die from prostate cancer in 2023. Prostate cancer is most commonly first identified by an elevated PSA level.
The PSA test was first approved in 1986 and became widely used to screen for prostate cancer in the 1990’s. With widespread screening came a dramatic increase in the number of new prostate cancer diagnoses that peaked in 1992 at 225 per 100,000 population, as shown by the light green squares in the graph below.
But despite all of these new cancers being found, there initially was no significant reduction in the prostate cancer death rate, as shown by the dark green triangles in the graph above. The implication was that the PSA test was finding lots of very low-grade, slow-growing cancers that were never going to spread during a man’s life. This raised a concern that we were doing a lot of unnecessary prostatectomies on men who did not need them… and prostatectomies have a significant risk of causing urinary incontinence and impotence. In addition, at the time, an elevated PSA was followed by a transrectal prostate biopsy that carried with it a 2-4% incidence of sepsis and further concern was raised that we were subjecting a lot of men to unnecessary biopsies. The enthusiasm for universal PSA testing began to wane and then in 2009, the PLCO study was published in the New England Journal of Medicine that caused many physicians to stop screening for prostate cancer altogether.
The PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) examined 76,693 men American men who were randomized to either get annual PSA tests for 6 years or get “usual care”. After 7 to 10 years, there was no difference in prostate cancer mortality between the two groups and it was concluded that annual PSA testing does not lower the death rate from prostate cancer. As a result, in 2012, the United States Preventive Services Task Force (USPSTF) gave the PSA a grade “D” recommendation, meaning that the harm of testing outweighed the benefits of testing. Overnight, prostate cancer screening braked to a halt. A second study in 2009 from Europe looked at 182,000 men randomized to either be screened every 4 years with a PSA or to not be screened. This study did find a 20% reduction in prostate cancer deaths in the group undergoing screening but the USPSTF chose to base its decision on the U.S. study rather than the European study.
But then in 2016, it came to light that in the PLCO, 90% of the men randomly assigned to the “usual care” group actually had a PSA test before or during the PLCO study by their regular physicians. In other words, both groups of men were getting screened using the PSA. It is not surprising, therefore, that there was no difference in the prostate cancer survival between the two groups in the PLCO study. This new revelation was published as a letter to the editor in the New England Journal of Medicine in 2016 and thus did not get as widespread attention as the original PLCO study 7 years earlier. Another important feature of the PLCO study was that only 4% of subjects were African American (who have a higher risk of prostate cancer) whereas in the U.S. as a whole, 12% of men are African American. In 2018, the USPSTF published new prostate cancer screening guidelines upgrading the PSA test to a grade “C” recommendation that stated “The decision to be screened for prostate cancer should be an individual one.” In other words, the USPSTF left it up to each doctor to decide whether or not to screen any given man for prostate cancer using a “shared decision making” approach.
In the past five years, there have been 4 new studies of PSA screening that have all shown that screening reduces prostate cancer death, ranging from 1 death prevented for every 101 men screened to 1 death prevented for every 570 men screened. Taken together, the data to support PSA screening is looking better and better every year.
Since the peak use of the PSA to screen for prostate cancer in 1992, there have been a number of developments that have changed our approach to the diagnosis and treatment of prostate cancer:
- The open radical prostatectomy has been largely replaced by the minimally invasive robotic prostatectomy which has lowered the complication rate of surgery.
- Advances in radiation therapy have led to radiation therapy now being a non-surgical treatment option for many men with prostate cancer.
- There is greater recognition that certain men are at significantly higher risk of getting prostate cancer and of dying from prostate cancer. These include African Americans, those with a family history of prostate cancer, those with the BRCA gene and those with another genetic condition called Lynch syndrome. In addition, men who develop prostate cancer at a young age are more likely to have aggressive, fatal prostate cancer than those who develop it during older ages.
- The prostate MRI has emerged as the preferred initial test for men with an elevated PSA and this has reduced the need for subsequent biopsy by 28%.
- The transrectal prostate biopsy that carried with it a 2 – 4% risk of sepsis has been largely replaced by the less risky transperineal prostate biopsy which has a < 1% risk of sepsis.
- There are new androgen-deprivation treatments and chemotherapies for patients with metastatic prostate cancer that can significantly prolong survival.
The net result of all of these developments in addition to the use of PSA testing has been a reduction in the mortality rate of prostate cancer from 39.2 per 100,000 men in 1992 to 18.6 per 100,000 men in 2020. That is a 50% reduction in mortality!
So who should we screen in 2023?
It remains true that many men with prostate cancer have slow-growing cancers that will never require any treatment. In these men, if you find a prostate cancer, you probably are not going to treat it and knowledge of the cancer only causes the man anxiety. Screening these men violates the cardinal rule of “Don’t ask a question that you don’t want to know the answer to“. Our challenge is to preferentially screen only those men who are at higher risk of developing a prostate cancer that will actually kill them. The current USPSTF recommendations of “shared decision making” between the primary care provider and the patient is vague and nebulous. It can leave the physician with the sense that the USPSFT is just saying “We really don’t know what to recommend, so you decide“. In order to provide a bit more direction, here are my personal recommendations:
- PSA testing starting at age 40: African American men, men with a family history of prostate cancer, men with BRCA1 or BRCA2 gene and men with Lynch syndrome.
- PSA testing starting at age 50: all other men.
- Don’t do a rectal exam as part of screening (reserve it only for those men with an elevated PSA).
- Repeat the screening PSA every 1-2 years.
- Stop PSA testing in most men at age 70 or in men with less than 10 years to live. For exceptionally healthy men, continued screening into their 70’s is prudent.
There are a few other caveats to PSA screening. Do not do a PSA test in a man with a urinary tract infection (false positives). If the PSA is elevated, the next step is usually to just repeat the PSA in 4 – 6 weeks (there are other reasons for false positives). What constitutes an elevated PSA depends on the man’s age: PSA > 2 in their 40’s, PSA > 3 in their 50’s & 60’s, PSA > 4 in their 70’s. Not every elevated PSA is from prostate cancer – chronic prostate inflammation, prostatic hypertrophy, and prostate trauma can also cause a high PSA level.
For a more in-depth update on PSA testing, you can watch a recent OSU MedNet webcast on prostate cancer screening by the Ohio State University’s Dr. Shawn Dason by clicking here.
Getting back to the hospital’s Community Day
Should you offer PSA testing as part of a cancer screening program at a hospital community day or health fair? I think that the answer is “Yes!”. However it should be targeted to men between the ages of 50 – 70 years old. For those men with risk factors (African American, family history, genetic predisposition), an age range of 40 – 70 is preferred. Screening should be accompanied by a discussion with the patient that not every man with an elevated PSA will have prostate cancer and not every prostate cancer has to be treated. That discussion should also include that prostate MRI and transperineal biopsy can now be done instead of the older transrectal biopsy, resulting in fewer complications.
The PSA pendulum has swung from screen all men to screen no men and most recently to screen some men. I believe that the pendulum is now swinging towards screening all men at an appropriate age. Primary care providers should get ahead of the pendulum and implement these screening practices now.
June 23, 2023