USPSTF (US Preventive Services Task Force) has recommended against PSA-based screening for prostate cancer, what they class as a Grade D recommendation. The task force adds that its recommendations apply to adult American males who have no symptoms which point towards prostate cancer – the recommendation includes any age, family history or race. The Task Force Stresses that it did not examine PSA-test usage to help diagnosis in males with symptoms that point to highly suspicious prostate cancer.

Grade D Recommendation means: “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.”

The Task Force added that its recommendations do not apply to PSA-test surveillance usage after diagnosis or treatment for prostate cancer.

15.9% of American males will have developed prostate cancer during their lifetime. In the majority of cases, prostate cancer has a good prognosis, while some are aggressive. The Task Force explains that a man’s lifetime risk of dying from prostate cancer is 2.8%. It is a disease that very rarely affects men before they are fifty years old. Death from prostate cancer is extremely rare among men aged up to sixty years. The vast majority of prostate cancer deaths occur when the man is at least seventy-five years old.

Current prostate cancer screening methods include testing for serum PSA levels, a digital rectal exam, and/or ultrasonography.

The Task force wrote:

“The evidence is convincing that PSA-based screening programs result in the detection of many cases of asymptomatic prostate cancer.

The evidence is also convincing that the majority of men who have asymptomatic cancer detected by PSA screening have a tumor that meets histological criteria for prostate cancer, but the tumor either will not progress or is so indolent and slow-growing that it will not affect the man’s lifespan or cause adverse health effects, as he will die of another cause first.

The authors say it is hard to determine how prevalent overdiagnosis is with any type of screening and treatment program.

The more prostate diagnoses there are, the higher the rate of prostate cancer overdiagnosis there is. One study found that 25% of men were diagnosed with prostate cancer after undergoing PSA screening and then a biopsy.

Overdiagnosis, the authors say, is much more probable among older patients with shorter life expectancies.

The Task Force’s main aim was to assess mortality from prostate cancer in all prostate cancer screening studies. The main goal of prostate cancer screening is to minimize prostate cancer death rates.

It is clear that for males aged at least seventy years, screening does not reduce death rates from prostate cancer.

For men aged between 50 and 69 years, evidence is compelling that after screening the reduction in mortality is small to none.

There are three categories of screen-detected prostate cancer, the authors explain:

  • Patients died regardless of early diagnosis and intervention
  • Patients’ survival rates improved because of early diagnosis and intervention
  • Patients whose outcomes were good, regardless of whether or not they had screenings, because of indolent tumors

95% of males with prostate cancer that was detected as a result of a PSA test, did not die prematurely due to that cancer – this figure includes those who received no definitive treatment.

The chances of a lower death rate from prostate cancer among males whose cancer was detected by PSA screening is extremely small, compared to those who waited for detection. The authors add that any potential benefit is long in coming.

There is not one study that has demonstrated a drop in all-cause mortality due to screen-detected cancer, this includes assessing studies individually as well as combining them with other screening studies.

PSA screening – about 80% of positive PSA tests are false positives when a cut-off point of 2.5-40 ng/ml is used. False positive PSA test results are closely linked to psychological effects, such as a persistent worry about prostate cancer.

A man with a false-positive test result has a higher probability of ordering further tests during the following 12 months, compared to patients with negative results. Examples of further tests include biopsies.

15% to 20% of all patients will have an abnormal PSA result that leads to a biopsy – this depends on the PSA threshold and how long the intervals are between tests.

68 in every 10,000 biopsies cause problems in some men, including transient urinary problems, bleeding, infection and fever.

PSA-based screening, according to studies examined by the Task Force, lead to considerable overdiagnosis of prostate tumors.

Definition of overdiagnosis in this document – a tumor is there, but despite its pathological characteristics, it does not progress to illness and/or death during the patient’s lifetime.

A high proportion of males who are diagnosed with prostate cancer are treated immediately. A man with an indolent tumor who is treated immediately cannot benefit from that treatment, but may suffer the risks associated with treatment.

The Task Force wrote:

“The USPSTF considered the magnitude of these screening-associated harms
to be at least small.”

Harms from treatments triggered by screen-detected cancer – studies have shown that almost 90% of patients with PSA-detected prostate cancer receive treatment straight away, which may include radiotherapy, surgery or androgen deprivation therapy.

Of 1,000 men who undergo prostate cancer surgery, up to 5 die within one month and between 10 and 70 experience serious complications (but do not die).

Patients who undergo radiotherapy or surgery have a serious risk of subsequent erectile dysfunction and/or urinary incontinence. Several studies have placed this risk at between 200 and 300 per 1,000. Radiotherapy is also linked to bowel dysfunction risk.

Even though not an FDA-approved indication, some doctors have used androgen deprivation therapy with patients whose prostate cancer is in its early stages, especially if the patient is older. This therapy has not been proven to improve clinical outcomes in prostate cancer that has not metastasized. However, studies have demonstrated that approximately 400 in every 1,000 males treated with androgen deprivation therapy for localized prostate cancer suffer from erectile dysfunction. Other side effects include hot flashes and gynecomastia (breast enlargement).

Even among patients with advanced prostate cancer, there is some evidence linking androgen deprivation therapy with a higher risk of myocardial infarction and coronary heart disease, fractures and diabetes. These risks for patients with localized prostate cancer undergoing androgen deprivation therapy have not been well studied.

Many more patients are diagnosed and treated for prostate cancer because of PSA-based screening – meaning, a great many more patients being subjected to treatment-related adverse events.

The authors wrote:

“Overdiagnosed men cannot reap benefit from the intervention, but are subject to all of the related risks of surgery, radiation, or hormone therapy. As such, overtreatment represents a critical consequence of PSA-based screening as currently utilized, most notably in the context of a high propensity for physicians and patients to elect to treat most cases of screen-detected cancer.

Even for those men whose screen-detected cancer would otherwise have been later identified symptomatically, a high proportion experience the same outcome, and are thus subjected to the harms of treatment for a much longer period of time. The evidence is convincing that PSA-based screening for prostate cancer results in considerable overtreatment.

The magnitude of these treatment-linked harms are considered to be at least moderate, according to the USPSTF.

The belief that PSA-based prostate cancer detection results in longer survival rates is not backed up by scientific evidence.

If there are any benefits, they are tiny after ten years. In fact, all the two largest trials every did, was to underline the uncertainty of the exact effects of screening.

In the two largest trials:

  • The European trial found a 0.06% absolute reduction in prostate cancer deaths for males aged between 50 and 74 years – a statistically insignificant reduction
    (6. Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, et al. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2011 Oct 7.)
  • The US trial found a 0.03% absolute rise in cancer deaths – a statistically insignificant increase.
    (Lin K, Croswell JM, Koenig H, Lam C, Maltz A. Prostate-Specific Antigen-Based Screening for Prostate Cancer: An Evidence Update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 90. AHRQ Publication No. 12-05160-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2011.)

A study which looked at a number of studies and combined the results (meta-analysis) also found no statistically significant drop in prostate cancer death rates. (Ilic D, O’Connor D, Green S, Wilt TJ. Screening for prostate cancer: an updated Cochrane systematic review. BJU Int. 2011;107:882-91).

However, an enormous number of men have had to undergo overtreatment and overdiagnosis of prostatic tumors that will not cause early death or serious illness, and suffer the adverse events that come with such interventions.

Members of the USPSTF wrote:

“Although about 90% of men are currently treated for PSA-detected prostate cancer in the United States – usually with surgery or radiotherapy – the vast majority of men who are treated do not have prostate cancer death prevented or lives extended from that treatment, but are subjected to significant harms. “

The Task Force came to the conclusion that “there is moderate certainty” that the pros in favor of PSA-based screening for prostate cancer are less than the cons – in other words, the harms probably outweigh the benefits.

The Task Force says that its recommendation applies to the general male US population. Although older males have a higher risk of developing prostate cancer, PSA-screening does not appear to provide this older age group with any greater benefits than harms either.

The authors added:

“However, the observed risk differences for race/ethnicity or family history are each relatively small when compared with the risk differences seen with increasing age, and there are no data that suggest that the net benefit of PSA-based screening is altered by race or family history. “

The USPSTF stressed that it did not examine the benefits and harms related to PSA screening for patients with symptoms that are highly suspicious of the disease. Neither did they look at PSA screenings for monitoring patients after they have been treated or diagnosed with prostate cancer.

Written by Christian Nordqvist