Editing AUA: Prostate Cancer Screening (2018)

AUA GUIDELINE: PROSTATE CANCER SCREENING 2018

See Original Guideline

See 2017 CUA Guideline Notes on Prostate Cancer Screening

See Prostate Cancer Screening on Chapter Notes


This document does not make a distinction between early detection and screening for prostate cancer

The guideline statements listed in this document target men at average risk, defined as a man without risk factors (see below)

The available evidence base permitted the Panel to recommend screening with limited confidence in the target group age 55 to 69 years. This age range represents the group with the highest quality evidence of benefit. The evidence from screening men under age 50 or over 69 years is very scarce

The AUA guideline panel interpretation of the evidence differs from that of a public health perspective. The AUA guideline panel interpreted the evidence from the perspective of the individual with emphasis on the information (both benefit and harm) that an asymptomatic man would need to make an informed decision about prostate cancer screening

Evidence base

In a 2013 systematic review, 6 well known randomized trials addressed the question of mortality benefit of prostate cancer screening. This guideline’s literature search is to November 2017

3 trials (PLCO, ERSPC, Goteborg) are considered relevant due to limitations of the Stockholm, Quebec, and Norrkoping trials (See Prostate Cancer Screening Chapter Notes).

The PLCO and ERSPC randomized trials ultimately addressed different questions: screening versus no or little screening in ERSPC as compared to annual screening versus usual care in the PLCO trial. A modest effect of PSA screening versus none in PLCO implies that a substantially larger study than PLCO is needed to meaningfully test more versus less frequent screening. Thus, PLCO was underpowered to address the question of organized versus opportunistic screening. The Panel interprets the randomized evidence to indicate that the ERSPC trial reflects the effect of PSA screening in a situation with low background screening and the estimate for the effect of screening (versus no screening) on prostate cancer-specific mortality was obtained from the ERSPC trial.

Benefits of PSA screening

Reduced prostate-cancer specific mortality

Risk of dying of prostate cancer is about 3% over a lifetime on average

Numbers needed to invite to screen and additional number needed to diagnose to avoid one prostate cancer death in the ERSPC (11 years of follow-up) and the Goteborg (14 years of follow-up) studies are as follows: 1,055 to invite and 37 to diagnose, 293 to invite and 12 to diagnose, respectively. However, these estimates are extremely sensitive to follow-up duration and are likely to be much lower over the long term

Several studies have revealed a significant reduction in prostate cancer specific mortality rates attributable to PSA-based screening for prostate cancer.

Population-based studies have found that the introduction of PSA-based prostate cancer screening was followed by subsequent dramatic reductions in prostate cancer mortality.

Reduced risk of metastatic disease

Prostate cancer specific mortality was the primary endpoint for both the ERSPC and the PLCO trials. However, one cannot ignore the benefits of earlier detection through screening in decreasing the risk of metastatic disease.

In ERSPC, the cumulative risk of metastatic disease at 9 to 11 years of follow-up was 31-33% lower in the screened arm compared to the control arm. The Goteborg arm of the trial demonstrated a 56% reduction in risk of metastatic disease

Lower stage and grade of cancer at diagnosis

Almost all of the randomized studies that have evaluated PSA-based screening for prostate cancer have demonstrated a benefit in terms of lower stage and grade of cancer at diagnosis

Potential harms of screening

The transrectal or transperineal prostate biopsy has risks of hematuria, hematochezia, hematospermia, dysuria and retention, pain and infection. Hematuria and hematospermia are the most frequently observed side effects with wide variation in observed rates. Hematospermia after biopsy occurs in 10-70% of patients while hematuria is seen 14-50% of the time.

While the risk of hospitalization due to bleeding complications remains low, infectious complications are increasing steadily over time, possibly due to fluoroquinolone resistance. The 30-day risk of hospitalization after biopsy for any cause has been estimated to be approximately 4%, of which 3/4 are for infections. The use of routine fecal culture and sensitivity tailored antibiotic prophylaxis may be one approach to reduce infection rates.

Modeling studies have yielded the following inferences that are particularly pertinent for screening policy development. First, PSA screening yields survival benefits that have contributed, to some extent, to the dramatic and sustained drop in prostate cancer death rates in this country. Second, PSA screening advances prostate cancer diagnosis by five to six years on average. Approximately one in four screen-detected cases reflects overdiagnosis. Strategies that screen less frequently than every year, and even less frequently for men with low PSA levels, are likely to be of value in reducing costs and harms while preserving most of the potential benefit of PSA-based screening.

In 2018, USPSTF used modeling studies in the development of the most recent grade C recommendation for PSA-based prostate cancer screening

Grade C: selectively offering or providing this service to individual patients based on professional judgment and patient preferences

Biopsy trigger

Much effort has been invested in the discovery of methods for improving the ability of PSA to predict the presence of prostate cancer. At this point, the use of DRE, PSA derivatives (PSA density and age specific reference ranges) and PSA kinetics (velocity and doubling time), PSA molecular forms (percent free PSA and proPSA), novel urinary markers (PCA3), and prostate imaging should be considered secondary tests (not primary screening tests) with potential utility for determining the need for a prostate biopsy, but with unproven benefit as primary screening tests.

The Panel recognizes that these tests can be used as adjuncts for informing decisions about the need for a prostate biopsy –or repeat biopsy- after PSA screening, but emphasizes the lack of evidence that these tests will increase the ratio of benefit to harm.

Further, risk calculators that include multiple variables (in addition to PSA) as an aid to predicting the risk of prostate cancer have not been proven to increase the benefit to harm ratio, and their value in predicting cancer on biopsy is not necessarily generalizable to a population that differs from that in which the tool was developed. No defined threshold based on calculator as to when to biopsy

Statements

PSA screening is NOT RECOMMENDED in men under age 40

PSA screening is NOT RECOMMENDED in men between ages 40 to 54 years at average risk.

Certain higher risk subgroups of men age 40 to 54 years may benefit from earlier screening, such as:

Men of African American race

Those with a family history of metastatic or lethal adenocarcinomas (e.g., prostate, male and female breast cancer, ovarian, pancreatic) spanning multiple generations, affecting multiple first-degree relatives, and that developed at younger ages (age < 55)

For such men, decisions regarding prostate cancer screening should be individualized

However, neither is screening is explicitly actively discouraged in these men

For men age 55 to 69 years, shared decision-making and proceeding based on men’s values and preferences is STRONGLY RECOMMENDED

For men ages 55 to 69 years the Panel recognizes that the decision to undergo PSA screening involves weighing the benefits of reducing the rate of metastatic prostate cancer and prevention of prostate cancer death against the known potential harms associated with screening and treatment.

This recommendation is in line with the updated 2018 USPSTF grade C recommendation, which states that the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one for men aged 55 to 69 years

Screening in men with < 10-15 year life expectancy will be less beneficial, if beneficial at all.

It should also be noted that multiple approaches subsequent to a PSA test (urinary and serum biomarkers, imaging) are available for identifying men more likely to harbor a prostate cancer and/or one with an aggressive phenotype. The use of novel markers, imaging, and/or risk calculators can be considered for prostate biopsy decisions in men with a suspicious PSA level to inform biopsy decisions.

A routine screening interval of 2 years or more may be preferred over annual screening

Modeling studies have projected that screening intervals of 2 years will preserve most of the benefits of screening and reduce the harms (i.e., false positive tests and overdiagnosis) when compared with screening every year.

PSA screening in men > age 70 years or any man with < 10-15 year life expectancy is NOT RECOMMENDED

There is a small subgroup of men over age 70 years who are in excellent health may benefit from PSA screening

In order to identify the older man more likely to benefit from treatment if screening takes place, the Panel recommends two approaches:

Increasing the prostate biopsy threshold based on evidence that men with a PSA level above 10ng/mL are more likely to benefit from treatment of prostate cancer when compared to those with a PSA below 10ng/mL

Discontinuation of PSA screening among men with a PSA < 3ng/mL, given evidence that these men have a significantly lower likelihood of being diagnosed with a lethal prostate cancer during the remaining years of life when compared to men with a PSA above 3ng/mL


Questions

When should screening be started?

What frequency should screening be taken at?

When should screening be stopped?

What are 3 benefits of prostate cancer screening?

What is the 30 day risk of hospitalization after prostate biopsy?

What is the current USPSTF grade recommendation for prostate cancer screening?

Answers

When should screening be started?

Age 55, younger if increased risk

What frequency should screening be taken at?

Every 2 years

When should screening be stopped?

Life expectancy < 10-15 years

Age 70

What are 3 benefits of prostate cancer screening?

What is the 30 day risk of hospitalization after prostate biopsy?

What is the current USPSTF grade recommendation for prostate cancer screening?