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Prostate cancer screening with prostate-specific antigen (PSA) test: a clinical practice guideline

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3581 (Published 05 September 2018) Cite this as: BMJ 2018;362:k3581

Population

Diagnostic pathway for prostate cancer Localised Stage I or II Stage III or IV Advanced Abnormal biopsy and staging No cancer diagnosis Normal biopsy Still possible to have a biopsy and be diagnosed, based on clinical suspicion No Biopsy Biopsy Normal PSA Elevated PSA or Choices considered in this comparison Prostate-specific antigen (PSA) screening No PSAscreening Width of lines proportional to approximate numbers of people Subsequent treatment Surgery Radiation Active surveillance With or withouthormonal therapy Can be followed byradical treatment Men without a previous diagnosis of prostate cancer considering screening

Comparison

or Screening No screening Screening No screening Using prostate-specific antigen testing

We suggest against systematic PSA-based screening for prostate cancer. Either option is reasonable. Shared decision making is needed for men considering screening. Moredetails Strong All or nearly all informed people would likely want this option. Benefits outweigh harms for almost everyone. Weak Most people would likely want this option. Benefits outweigh harms for the majority, but not for everyone. Weak Most people would likely want this option. Benefits outweigh harms for the majority, but not for everyone. Strong All or nearly all informed people would likely want this option. Benefits outweigh harms for almost everyone.

Comparison of benefits and harms

All evidence

With screening With no screening Evidence quality Events per 1000 people Within 10 years No important difference The panel found that these differences were not important for most patients, because the intervention effects were negligible and/or very imprecise (such as statistically not significant)

No important difference All cause mortality Moderate More 129 128

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably has little or no effect on all cause mortality

No important difference Prostate cancer mortality Low More 3 3

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency Serious Publication bias No serious concerns PSA screening may have little or no effect on prostate cancer mortality

7 fewer Incidence of cancer (any stage) Low More 32 39

Risk of Bias Serious Imprecision Because of inconsistency Indirectness No serious concerns Inconsistency Serious Publication bias No serious concerns PSA screening may increase the detection of prostate cancer (any stage)

7 fewer Incidence of localized cancer Low More 19 26

Risk of Bias Serious Imprecision Because of inconsistency Indirectness No serious concerns Inconsistency Serious Publication bias No serious concerns PSA screening may increase the detection of localized cancer (stage I or II)

Incidence of advanced cancer Low More 13 11 No important difference

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency Serious Publication bias No serious concerns PSA screening may have little or no effect on the detection of advanced cancer (stage III or IV)
Within 1 month

Fewer Biopsy-related complications Low More

Among 1000 men with PSA screening, more presented with complications due to prostate biopsies: Blood in semen: 94 Pain: 45 Fever: 19 Hospitalized for sepsis: 1 Blood in urine: 67 Because of uncertainty due to estimating likelihood along the diagnostic pathway
At any time

Fewer Cancer treatment complications Low More

Among 1000 men with PSA screening, more presented with complications due to cancer treatment: Erection not firm enough for intercourse: 25 Urinary incontinence: 3 Because of uncertainty due to estimating likelihood along the diagnostic pathway
See patient decision aids
See all outcomes

Selected evidence at lower risk of bias This section includes only data from the ERSPC trial, conducted in 162 243 participants in 9 European countries

With screening With no screening Evidence quality Events per 1000 people Within 10 years No important difference The panel found that these differences were not important for most patients, because the intervention effects were negligible and/or very imprecise (such as statistically not significant)

No important difference Moderate More 129 129 All cause mortality

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably has little or no effect on all cause mortality

1 fewer Moderate More 3 2 Prostate cancer mortality

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably leads to a small reduction in prostate cancer mortality

18 fewer Moderate More 32 50 Incidence of cancer (any stage)

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably increases the detection of prostate cancer (any stage)

14 fewer Moderate More 19 33 Incidence of localized cancer

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably increases the detection of localized cancer (stage I or II)

13 Moderate More 3 fewer 10 Incidence of advanced cancer

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably slightly decreases the detection of advanced cancer (stage III or IV)
Within 1 month

Low More Biopsy-related complications Fewer

Among 1000 men with PSA screening, more presented with complications due to prostate biopsies: Blood in semen: 94 Pain: 45 Fever: 19 Hospitalized for sepsis: 1 Blood in urine: 67 Because of uncertainty due to estimating likelihood along the diagnostic pathway
At any time

Low More Cancer treatment complications Fewer

Among 1000 men with PSA screening, more presented with complications due to cancer treatment: Erection not firm enough for intercourse: 25 Urinary incontinence: 3 Because of uncertainty due to estimating likelihood along the diagnostic pathway
See patient decision aids
See all outcomes

Men with family history of prostate cancer Family history defined positive if man’s father or at least one brother had been diagnosed with prostate cancer

With screening With no screening Evidence quality Events per 1000 people Within 10 years No important difference The panel found that these differences were not important for most patients, because the intervention effects were negligible and/or very imprecise (such as statistically not significant)

29 fewer Incidence of cancer (any stage) Moderate More 50 79

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably increases the detection of prostate cancer (any stage)

19 fewer 25 Incidence of localized cancer Moderate More 44

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably increases the detection of localized cancer (stage I or II)
See patient decision aids
See all outcomes

Men of African descent

With screening With no screening Evidence quality Events per 1000 people Within 10 years No important difference The panel found that these differences were not important for most patients, because the intervention effects were negligible and/or very imprecise (such as statistically not significant)

Prostate cancer mortality Moderate More 7 1 fewer 6

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably has little or no effect on prostate cancer mortality

29 fewer Incidence of cancer (any stage) Moderate More 51 80

Risk of Bias Serious Imprecision No serious concerns Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns PSA screening probably increases the detection of prostate cancer (any stage)
See patient decision aids
See all outcomes
Men with these characteristics carry a higher incidence of prostate cancer, and could be at higher risk of dying of prostate cancer. It remains uncertain whether the impact of screening is similar in these higher risk men in comparison to men at lower risk. Men at higher risks There is considerable variability among men's values and preferences regarding prostate cancer screening. Men who place a high value in avoiding complications from biopsies and subsequent treatment are likely to decline screening. In contrast, men who place a higher value in even a small reduction of prostate cancer mortality may opt for screening. Higher risk patients may be more likely to seek screening because they may worry more about prostate cancer and want to rule out the diagnosis. Values and preferences LUTS symptoms like these are common complaints in adult men that can have a major impact on quality of life and substantial economic burden. The aetiology of LUTS is multifactorial, benign prostatic enlargement, due to hyperplasia, being the major cause. Evidence to date indicates that men with LUTS are at no higher risk of prostate cancer than men without LUTS. Lower Urinary Tract Symptoms (LUTS) Key practical issues PSA testing is done with a regular blood sample Usually taken through rectum guided by ultrasound Takes about 5-10 minutes Antibiotics given before procedure Local anaesthesia or sedation given before procedure May have to stop blood thinners before procedure Screening If biopsy is required Slow stream Sensation of incomplete emptying Increased urinary frequency Family history of prostate cancer African descent Poorer socio-economic groups

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Rapid Response:

Re: Prostate cancer screening with prostate-specific antigen (PSA) test: a clinical practice guideline

Earlier this year I was most perplexed by some of the NHS campaigns to promote cancer awareness and left fearful that they may have caused more harm than good.

They do appear to be, on occasions, ill designed.

For instance, at that time I was literally inundated by PSA requests following a most recent prostate cancer campaign.

In the well-known advertisement at that time there was no mention whatsoever about age target, for instance.
To note that, not in the UK, where the test is free under the NHS scheme, I came across ads promoting its request, at a "fee", to "exclude" prostate cancer.

Some of the readers may recall a similar campaign about lung cancer inviting the general population, once again without any mention of age and smoking habits, to be checked by their own GP for a cough lasting more than 3 weeks as this could have been an indicator of cancer.

In both cases, most patients I have seen in response to the campaigns were below 40 years of age and in some occasions in their early 20s, often non-smokers. In fact, following the campaign about lung cancer, I do not recall having seen any heavy smoker with subacute or chronic cough coming to see me in response to the advertisement.

First of all, I think it should be stressed that cancer markers should never ever been used alone to diagnose cancer in asymptomatic patients or be presented misleadingly as such.

The case of the PSA suggests that it would be in the NHS interest promoting courses for GPs - and not only - about tumour markers and their use in clinical practice.
Around that time I received an invitation from the Italian Ministry of Health to take an online distance course on the topic - FREE.
It is a must, yet it rewards you with CME points for 10 hours of study. No points if you do not pass.
There are questions and the questions do change. So, if you get it wrong, I am afraid, you have got to do it all over again.
Few “souls” would argue that this type of course would not be helpful to NHS GPs and Consultants considering how often markers have been used in a not purely orthodox way.
I am sure the NHS would ultimately save money and that it would be beneficial to the patients (overdiagnosis and not just).

Unfortunately, practising in the NHS appears to be an “atypical” business and it is far easier to find “free courses” indirectly promoting some “new prescription”, or “procedure”, than an educational activity that could improve care and cut costs.

With specific reference to the PSA, Australian PSA testing guidelines also recommend that fully informed testing should commence at 45 years of age only for men with a family history of prostate cancer.

But the story is more complicated than that so much so that no one, anywhere in the World, has put in place automatic screening procedure for prostate cancer as it has been done for cervical, breast, and colonic cancer.

And this is the case for valid reasons.

What we know is that most men with an elevated PSA will proceed to biopsy. About one in four prostate biopsies will find prostate cancer, while the risk of significant bleeding or infection is 1% to 4% of patients. For those diagnosed with prostate cancer, approximately 90% will elect to have some sort of intervention. This includes surgery, radiation therapy, or androgen deprivation. All of these treatments may be associated with adverse effects, such as urinary, bowel and erectile dysfunction. Many patients may consider the adverse effects to be acceptable trade-offs for a procedure they regard as “lifesaving”. There is also the argument, that any morbidity associated with intervention, is better than the morbidity from metastasised prostate cancer.

That being said, a large study published in the NEJM in late 2016 showed how the comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. At a median of 10 years, prostate-cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments.

It gets worse than that.

It has been argued that up to 50% of the prostate cancers detected would not have caused illness in the man’s lifetime. Therefore, for 50% of men any adverse effects from any intervention can be considered a harm.

Another, and perhaps even more grave downside of poorly designed awareness campaign is forgetting the impact they may have on the services.

In fact, among the rather young and asymptomatic patients suddenly bringing to their GP's attention following a campaign failing to highlight a more specific target, there will be false positives, which at that point would have to be referred to Secondary Care which will have not increased its capacity just to deal with the temporary surge in demand. Accordingly, this will delay the diagnosis for those with cancer indeed.

Diagnostic errors may be more likely, and this should not come very much as a surprise.

In fact, let us think about the surge in x-ray requests following the campaign for lung cancer which brought to GP attention young worried well non-smokers coughing for 3 weeks.

Besides the risk of over-diagnosis, the sudden raise in the number of films to look at may well increase the risk of misdiagnosis and missed diagnosis.

It is time to invest in designing specific guidelines for prostate cancer screening and even more to invest in research about the behaviour of prostate cancer.

As we are finding to be the case in many tumours, we may be calling the entities the same that are as similar as apples and pears and which should be tackled in different ways in view of their biological differences and indeed differences in the hosts.

Speaking of cancer awareness campaigns, I appreciated the similar most recent campaign about obesity as a potential cause of cancer, but no patient attended because of that one.

Saying "you may have cancer" clearly is more of a powerful message than "you may develop cancer”.

I remain of the opinion that, in Primary Care, prevention is better and cheaper than cure 10 times out of 10.
Your paper "Prostate cancer screening with prostate-specific antigen (PSA) test: a clinical practice guideline" does not solve the dilemma of how to respond to conflicting information, but highlights how pressing the issue is.

Competing interests: No competing interests

07 September 2018
Edoardo Cervoni
Physician
LD4U Ltd.
Southport