Feeds:
Posts
Comments

Posts Tagged ‘Cancer Society’

PROSTABLOG NZ: It’s almost a year since the first hearings were held by the NZ Parliament’s Health Select Committee inquiry into the early detection and treatment of prostate cancer.

The obvious question now is when will it report back.

Since it published its terms of reference in August last year, the committee has received 33 submissions, four of them from the influential health lobby group, the NZ Guidelines Group, whose last submission was made in December.

This document made it clear that the group – an independent incorporated society originally set up by the government in 1996 – is opposed to population-based PSA screening.

To save one life, up to 41 men could incur significant harm.

It bases this view on its assessment of numerous NZ and international studies, including two large randomised trials (one European, the other American) that were reported last year.

Here are some of the last pages of the group’s December, 2009, submission (RCT = random controlled trial):

This also appears to be the main thrust of submissions on PSA testing from other health authorities (although the Guidelines Group is at pains to stress it is independent from the Ministry of Health).

Another “official” organisation, the National Health Committee, said in its submission (August 26, 2009) that it has seen nothing to change its 2005 advice to the MOH that population-based PSA screening is not an acceptable option.

However, it did favour targeted screening of high-risk groups, such as men with a family history of prostate cancer.

The NHC is aware that since providing its advice in 2005, clinical practice has found
that targeted screening for men at high risk of prostate cancer appears to be useful
and potentially cost effective. These are men who have a family history of prostate
or related cancers.

The Royal NZ College of General Practitioners – presumably speaking on behalf of doctors on the frontline – said in its submission it would go along with the NZ Guidelines Group’s views.

It did make a couple of pleas, however, calling for up-to-date information to hand out to patients, and for treatment to be available to all:

It is important that inequities in access relating to follow up after positive
screening results, and for symptomatic men, are identified and eliminated.

The Cancer Society agreed with the Guidelines Group, and backed this up by quoting from selected organisations in other Western countries.

Most agencies around the world have some form of recommendation that decisions for screening for prostate cancer should be made on an individual basis and in consultation with a medical professional:

The Australian Cancer Council states that:
“In the absence of direct evidence showing a clear benefit of population based screening for prostate cancer, a patient centred approach for individual decisions about testing is recommended. Screening discussions and decisions should always include and take into account, age and other individual risk
factors such as a family history of the disease” (Cancer Council Au 2005).

The American Cancer Society states that:
“The American Cancer Society (ACS) does not recommend routine testing for prostate cancer at this time. ACS believes that doctors should discuss the pros and cons of testing with men so each man can decide if testing is right for him. If a man chooses to be tested, the tests should include a PSA blood test and
DRE (digital rectal exam) yearly, beginning at age 50, for men at average risk who can be expected to live at least 10 more years.” (American Cancer Society 2009).

The UK Cancer Research Council states:
“in the UK, there is no national screening programme for prostate cancer because trials have not yet shown clear evidence that screening will reduce deaths from this disease. Also, many men diagnosed with
prostate cancer have very slowly growing cancers that will never cause any symptoms or problems in their lifetime. So at the moment there is no clear benefit in diagnosing prostate cancer early and it may actually cause harm for some men.”(Cancer Research UK 2009).

Urological Society of Australia and New Zealand states:
“Individual men aged 50 to 70 years with at least a 10 year life expectancy should be able to be screened by annual DRE and PSA testing, after appropriate counselling regarding the potential risks and benefits of investigations and the controversies of treatment.”(Urological Society ANZ 1999).

The majority of submissions – from prominent medical practitioners, prostate cancer lobby groups and patients – urged the committee to recommend PSA testing, if not on a population (all men) screening basis, then at least as a service offered routinely by GPs, without men having to ask (the current MOH policy).

Read Full Post »

JUNE 4: PROSTABLOG NZ: Any hopes the NZ Prostate Cancer Foundation and some top urologists may have that the government will change its mind  any time soon about promoting prostate cancer screening among men are not helped by a new NZ Medical Journal article. READ ARTICLE HERE>

There has been world-wide  renewal of the debate about population-based screening campaigns since publication in the New England Journal of Medicine in March of the results of a couple of long-term studies into whether PSA testing saves more lives.

The authors of the NZ article think the results support a long-held fear that PSA testing leads to “over diagnosis” and unnecessary treatment of slow-growing prostate tumours that were never going to do any harm.

The Otago University researcher and epidemiologist say:

“The results of the randomised controlled trials might optimistically be considered to indicate that: eventually there will be a reduction in prostate cancer mortality from PSA testing of asymptomatic men 55–69 years of age; the considerable harms from such testing are bearable by patients and the health care sector, and; PSA testing of asymptomatic men should be facilitated.

“Another view would be that we now have inconclusive evidence from randomised controlled trials of any decrease in prostate cancer mortality and unequivocal evidence of major harms, mainly from over-diagnosis and consequent overtreatment, so much so, that good health care should involve advising asymptomatic men against PSA testing at this time.”

The article is timely, since the Ministry of Health is due to release an updating statement on its prostate screening policy.

Its stance has been that a campaign like those for cervical and breast cancer screening is not appropriate for prostate cancer, given widely held views that it may do more harm than good.

This is a view shared by the Cancer Society, but not the prostate cancer foundation, whose president, Barry Young, has called the stance scandalous.

His opinion appears to be backed by statistics showing the death rate among Maori men from prostate cancer is twice that for non-Maori. The cervical and breast cancer campaigns feature TV advertisements clearly aimed at Maori and Pacific Island women.

Recent US studies show poorly educated men in lower socio-economic groups fare worst from prostate cancer, as do black Americans.

The NZ Medical Journal article seems at odds with the American Urological Association’s recently updated guidelines, which urge men of 40 to be PSA-tested so a baseline for later comparison can be established (level change and speed of change are significant).

However, the AUA is equivocal about what the two studies reveal and stops well short of recommending population-based screening. It advises “well-informed” men to seek individual assessment by their physicians, a view held by the NZ Ministry of Health.

The ministry has been reviewing the studies. One of its committees discussed them on May 18 and has made a recommendation on screening to the Director General of Health, who is expected to make a statement as early as Monday.

This will undoubtedly assist the new Minister of Health, Tony Ryall, who contradicted himself when he announced new health targets in May. He made no mention of prostate cancer, despite his January statement that it would be a top priority for the new Government.

NZ Medical Journal, June 5, 2009:

PSA testing in asymptomatic men to diagnose prostate cancer remains experimental

By Brian Cox, Mary Jane Sneyd

The recent reductions in prostate cancer mortality seen in some countries have been attributed to earlier detection of the cancer by PSA testing.

However, the randomised controlled trials show that if any benefit from PSA testing exists it would not be seen within 7 years of its introduction.(1,2)Therefore, the mortality reductions observed are likely to be due to more cases being offered curative therapy or the availability of better treatment.

In 1996, PSA testing of asymptomatic men was considered experimental and the major potential for over-diagnosis and subsequent overtreatment with major sideeffects was highlighted3 and now the results of two studies have become available.

These results provide conflicting evidence of the effectiveness of PSA testing in reducing mortality from prostate cancer.

The results of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial in the United States were published because, at this time, the study’s monitoring board raised concerns about the harms they identified from PSA testing in asymptomatic men,(2) whereas the European Randomized Study of Screening for Prostate Cancer (ERSPC) study protocol precipitated publication when a statistically significant result was obtained from analyses conducted at regular intervals.(1)

A summary of the design of these two studies is shown in Table 1.

The ERSPC study was conducted in 7 countries, used various PSA cut-off points for recommendation for biopsy, varying screening intervals, and different age eligibility, with screening ceasing when the upper age of eligibility was reached.

In the PLCO trial, men aged 55–74 years were offered annual PSA testing for 6 years, combined with digital rectal examination for 4 years, or in the control arm received usual care.

Active annual follow-up by questionnaire and linkage to the National Death Index was undertaken with a median duration of follow-up of 11.5 years (range
7.2–14.8). The PSA assays for each PLCO trial centre were performed by one laboratory. A cut-off of 4ng/ml was used to recommend referral to their usual doctor.

Table 2 summarises the main results of these studies.

The results of the ERSPC study suggested a 20% reduction in prostate cancer mortality from PSA testing, along with other screening tests such as digital rectal examination (DRE) and transrectal ultrasonography (TRUS), in asymptomatic men after a median of 9 years of follow-up (RR=0.80, 95%CI 0.65–0.98).

Table 1. Summary of the design of the PLCO trial and the ERSPC study

Screening 1

The PLCO trial observed a non-significant 13% increase in prostate cancer mortality in those offered annual PSA tests (RR=1.13, 95%CI 0.75–1.70) after 7 years of follow-up for all subjects.

This was not significantly altered by inclusion of available data to 10 years of follow-up (67% of subjects) or if confined to those with one PSA test, or 2 or more tests, in the previous 3 years at baseline.

The chance of a diagnosis of prostate cancer increases with the number of biopsies taken.

In the ERSPC study the number of biopsies after a positive screening test varied between countries, but standardisation was recommended in 1996, whereas in the PLCO trial the decisions about biopsy and treatment were left to the man’s usual health care provider.

This meant that, in the PLCO trial, any further assessment procedures and treatment were expected to be similar for both the intervention and control group.(4)

Table 2. Summary of the PLCO trial and ERSPC study results of PSA screening for prostate cancer

Screening 2

In Finland, Sweden, and Italy, randomisation of the offer of screening occurred after selection from population registers – a study of the effect of the introduction of prostate screening in the general population (the effectiveness of screening).

In the Netherlands, Belgium, Switzerland, and Spain, randomisation occurred after acceptance of the invitation to participate—a study of screening in those who accept it (the efficacy of screening).

Efficacy is greater than effectiveness and effectiveness measures the overall benefit of offering PSA testing to asymptomatic men in the population.

Therefore, the ERSPC study estimate of benefit is greater than would be achieved from population-based PSA testing in asymptomatic men.

In the PLCO trial 40% of the control subjects had at least one PSA test by the second year of follow-up (contamination of the controls) and this increased to 52% by the sixth year of follow-up.

The contamination of the control group in the ERSPC study was not reported in the recent publication but varied from 6.7% to 36.6% among centres during 1996–2001.(5)

This resulted in a smaller relative increase in prostate cancer diagnoses between intervention and control groups in the PLCO trial (22%) compared to the ERSPC study (71%).

Detailed analyses of both the similarities and differences among the different trials included in the ERSPC study are likely in the future.

The beneficial effects from randomised controlled trials of screening almost always exceed what is obtained when the technology is introduced into routine health care, as the tight controls for the decision making process and management protocols of trials tend to be lost.

A greater length of follow-up of the trials will be required before more conclusive results are available. However, the contamination of the control groups in both studies may not have occurred equally among different risk groups for prostate cancer death, resulting in unresolvable bias.

What is now unequivocal from these two trials is the magnitude of over-diagnosis and subsequent overtreatment resulting from the PSA testing of asymptomatic men.

Overdiagnosis is the detection of prostate cancer that would not become clinical disease in a man’s natural life.

This is sometimes referred to as indolent prostate cancer and has been known for a long time to be very common.

This over-diagnosis has been estimated to be 48% (95%CI 44%–55%) for annual screening and 50% (46%–57%) for 4-yearly screening in men aged 55–67 years.(6)

The treatment of prostate cancer by either radical prostatectomy or radiotherapy carries significant risks such as chronic incontinence (urinary or faecal), impotence, or, in some instances, death.

In addition to significant side-effects, the treatment of many men who will not benefit produces increased waiting times and reduced accessibility to radiotherapy and surgery for other patients who may benefit from them.

For example, if we accept the ERSPC study results, 1480 men would need to be screened and 48 additional cases of prostate cancer treated for each death from prostate cancer prevented over a 10-year period.

Moreover, about 24 of the additional cases treated would receive treatment for a condition that would not have become clinical prostate cancer in their lifetime, and of these about 4 would have chronic incontinence or impotence.

The decision about the value of PSA testing in asymptomatic men is not solely determined by the magnitude of any reduction in prostate cancer mortality but by the balance of harms versus benefits.

Despite previous claims of effectiveness,(7,8) it now appears that if there is a reduction in prostate cancer mortality from PSA testing in asymptomatic men, it is likely to be small.

The current results of the trials assist in resolving the controversy regarding the value of PSA testing of asymptomatic men.

The results of the randomised controlled trials might optimistically be considered to indicate that: eventually there will be a reduction in prostate cancer mortality from PSA testing of asymptomatic men 55–69 years of age; the considerable harms from such testing are bearable by patients and the health care sector, and; PSA testing of asymptomatic men should be facilitated.

Another view would be that we now have inconclusive evidence from randomised controlled trials of any decrease in prostate cancer mortality and unequivocal evidence of major harms, mainly from over-diagnosis and consequent overtreatment, so much so, that good health care should involve advising asymptomatic men against PSA testing at this time.

It is easy to understand the belief that the early detection of cancer must result in a reduction in the mortality from the disease.

Historically, many clinicians and patients have been seduced by this idea many times for a variety of cancers.(9)

However, the current randomised controlled trial evidence suggests that claims of benefit from PSA testing in asymptomatic men have probably been overstated and that, as indicated by the authors of one of the trials,2 the recognised harms must be more rigorously considered to protect many men from iatrogenic illness.

Author information: Brian Cox, Associate Professor; Mary Jane Sneyd, Research Fellow; Hugh Adam Cancer Epidemiology Unit, Department of Preventive and Social Medicine, University of Otago, Dunedin.

Acknowledgement: Associate Professor Cox and Dr Sneyd were funded by the Director’s Cancer Research Trust.

Correspondence: Brian Cox, Hugh Adam Cancer Epidemiology Unit, Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand. Fax: +64 (0)3 4797164; email: brian.cox@otago.ac.nz

References:
1. Schroder FH, Hugosson J, Roobol MJ, Tammela TLJ, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine. 2009;360(13):1320–8.
2. Andriole GL, Crawford ED, Grubb RL, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine. 2009;360(13):1310–9.
3. Cox B. Prostate cancer screening is experimental. The New Zealand Medical Journal. 1996;109(1017):63–4.
4. Barry MJ. Screening for prostate cancer – the controversy that refuses to die. New England Journal of Medicine. 2009;360(13):1351–4.
5. Ciatto S, Zappa M, Villers A, Paez A, Otto SJ, Auvinen A. Contamination by opportunistic screening in the European Randomized Study of Prostate Cancer Screening. BJU International. 2003;92 (Suppl. 2):97–100.
6. Schroder FH. Detection of prostate cancer: the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The Canadian Journal of Urology. 2005;12 (Suppl. 1):2-6.
7. Lamb DS, Slaney D, Smart R, Nacey JN, Russell G, Scott B, et al. Prostate cancer: the new evidence base for diagnosis and treatment. Pathology. 2007;39(6):537–44.
8. Smart R. PSA testing and DRE, TRUS scanning with sector biopsy, improved histology, curative treatments, and active surveillance for prostate cancer: asuccess story for men’s health. New Zealand Medical Journal. 2008;121(1287):57–68.
9. Richardson AK. Prostate cancer screening: is it possible to explain diametrically opposed views? New Zealand Medical Journal. 2005;118(1209).

Read Full Post »

MAY 11: PROSTABLOG NZ:  Anyone doubting the significance of the two long-term prostate cancer testing studies just published in the US need only read a NZ Medical Journal paper published late last year by leading Kiwi urologist Robin Smart.

He accurately predicted the studies “may or may not” resolve debates about national screening and making more information available to GPs and patients.

The studies have had mixed reviews, but, as Smart says, they add to a vast body of knowledge that overwhelmingly supports the value of PSA, digital examination and biopsy testing.

He laments a lack of technology and promotion of information about testing in NZ that could save up to half the 600 men who currently die of proistate cancer here each year, a figure that is static, compared to big improvements in Western Europe, the US and Australia.

He says our government’s antagonistic attitude to prostate cancer information dissemination puts us with the backward practices of Eastern Europe, where adoption of modern methods and testing (including PSA), has resulted in increasing death rates.

He points out that statistics quoted to rebuff calls for national screening are well below those accepted for NZ breast and cervical cancer screening programmes.

His conclusions (full paper available to NZ Medical Journal subscribers only):

“An overwhelming body of evidence shows that PSA/digital rectal examination testing leading on to TRUS (ultrasound) biopsy and curative treatments (where indicated) has been a major advance for men’s health.

Indeed, those with significant experience of dealing with men with this cancer in pre-PSA times appreciate the difference only too well.

Then, 70% had metastases at diagnosis and the mortality ratio was 41%.

Studying the fate of control group men in the various trials outlined above, especially those in Bill-Axelson and Holmberg’s trial, provides a chilling reminder of the potential for this cancer to ruin or end a man’s life in his later years.

It is true that these improvements in morbidity and mortality have come at a price of more investigation and treatment. Numbers of men diagnosed with prostate cancer have approximately doubled.

But this is the inevitable price for better results. The first-line investigations of PSA, DRE, and TRUS biopsy have been shown to be well tolerated and safe in an office setting.

It is important that men with insignificant cancer, or major comorbidity, or limited projected lifespan, get appropriate management, including surveillance only or other minimal approaches. It is also important that men with threatening cancers get these recognised in time for curative treatment.

A special group are those with a family history of prostate cancer. The usual lifetime risk of 12% doubles if one first-degree relative has prostate cancer and increases by 5 to 7 times if more than one has it.  Therefore, potential benefit of PSA testing includes not just the individual but also his family, and there is evidence that the outlook for family members is improved by PSA/DRE testing.

Before PSA testing, the outlook was worse for those with a family history compared to the general population but now it is better. This is considered to be due to a greater awareness and earlier testing by relatives of those with prostate cancer.

The dramatic improvements in morbidity and mortality from prostate cancer in Western Europe, North America, and Australia outlined above have occurred because a very large proportion of the middle aged and older men in those countries have undergone PSA and DRE testing.

The drive for this remarkable change has occurred at community level amongst men, their families, and family doctors on learning about this technology as a way to avoid advancing prostate cancer.

Governments generally have been neutral or antagonistic about PSA testing.

For example, the British National Health Service states: “Opportunistic screening (with PSA) should be discouraged” and the New Zealand Guidelines Group (NZGG) in 2004 stated several times in its information for practitioners that PSA “Not recommended as a screening test in asymptomatic men.”

New Zealand has not shared the improvements in prostate cancer mortality experienced by other advanced Western nations including Australia detailed above. Rather, our annual mortality has been static at about 600, similar to eastern European countries.

Large numbers (more than 2000) of men are now diagnosed with prostate cancer in New Zealand each year. But there have been powerful discouragements to men contemplating PSA testing and their family doctors resulting in uncertainty and confusion.

This includes not just the efforts of the NZGG, but also studies originating in the New Zealand Ministry of Health critical of general practitioners screening with PSA and DRE.

Many general practitioners are ambivalent about it as a result. Some have adapted by only referring on men with higher PSAs, for example 8 or more. This author’s experience has been that the most recent 300 TRUS Biopsies have a mean referral PSA of 11.1, and the last 100 radical prostatectomies—a mean referral PSA of 8.4.

Others actively discourage PSA testing and disseminate that view.

A common argument used is that 450 men must be screened to save 1 from dying of prostate cancer (a figure which is disputed)—and that this is too large to make screening worthwhile.

But the equivalent figure for breast cancer screening is 1700, and that for cervical cancer screening 8000. It seems likely that New Zealand men have not been tested as much, and perhaps sometimes been referred later (compared to men in Australia, North America, and Western Europe), to explain the difference.

Access to investigations and treatments may be poorer in New Zealand than the other countries, especially for the two-thirds of the population without health insurance.

Of course, most New Zealand general practitioners exercise great care in dealing with this issue.

The NZGG this year (2008) formed an ‘advisory group’ comprising representatives of the Prostate Cancer Foundation, radiation oncologists, urologists (including this author), the Cancer Society, the College of Pathologists, general practitioner, and Maori to formulate more information material.

The “non-Ministry” members of this group strongly favoured the NZGG providing men contemplating PSA/DRE testing with information about the advances discussed above, including changes internationally in prostate cancer mortality and trials. It was considered that men making such a decision at this time were entitled to this information.

The institution of a national screening programme was not advised, but provision of this information to men was.

But the draft containing this advice was rejected, the NZGG citing its contract with the Ministry and opting for neutrality. An opportunity [was] lost to improve prostate cancer results in New Zealand as has occurred in other countries.

To be fair to the NZGG, other government authorities internationally have adopted a similar neutral or opposing stance. And, as with any field of human endeavour, papers continue to be published expressing scepticism about PSA/DRE screening.

The long-awaited analysis of the ERSPC and PLCO trials, already put off from 2008 for a few years, and which have cancer mortality as end points, may resolve the debates. Or may not. There are many potential problems with these huge multicentre trials, not least of which is occult cross over from control to PSA groups. Initial results, as discussed above, support PSA/DRE testing.

The weight of evidence in favour of PSA/DRE testing is now overwhelming after almost two decades of international experience. To go back to the time before PSA testing would now be unthinkable.

Of course we hope for the perfect tests, perfect treatment, and continue to look for improvements. But New Zealand men today need the benefit of current technology which the evidence shows could save between 200 and 300 of the 600 who currently die of prostate cancer each year.

Read Full Post »