Prostate Cancer Awareness – The Importance of Early Diagnosis

Professor Tony Costello in a Operation Room

Prostate Cancer Awareness – The Importance of Early Diagnosis

28 Jun, 2010

A Contemporary View – Myths and Reality 2003

Anthony J Costello, F.R.A.C.S., M.D.
Professor of Urology,
The Royal Melbourne Hospital
Department of Surgery, University of Melbourne
Director, Prostate Cancer Foundation of Australia

Level 4
Department of Urology
Grattan Street
PARKVILLE 3050

Suite 1.6
Epworth Hospital
89 Bridge Rd
RICHMOND 3121

ABSTRACT

Prostate cancer is the number one male cancer in Australia. It is the second commonest cancer death in men in this country. In the year 2000 there were approximately 2,700 deaths from prostate cancer and 12,000 cases of prostate cancer were diagnosed. This means that prostate cancer is equivalent in incidence and mortality to breast cancer. It is astonishing that there is such a low level of awareness of prostate cancer in the Australian community compared with the awareness of breast cancer and such a difference in attitude to testing for breast cancer compared to prostate cancer testing.

The clinical comparison between Breast Cancer and Prostate Cancer is startling. However there has been an almost nihilistic approach to Prostate Cancer, the view being that Prostate cancer is an old man’s disease – every man has it, and treatment is worse than the disease.

This article is a contemporary view demonstrating the lethality of prostate cancer, the importance of early diagnosis using PSA testing and need for increasing awareness in the community is highlighted.

ARTICLE

In 2001, approximately 70% of Victorian women and the age group at risk for breast cancer will have appropriate screening mammography. In Australia in the year 2001 only one in ten men will have appropriate prostate cancer testing.

Although there is significant government concern of the overuse of Prostate Specific Antigen (PSA) blood testing it appears that there is very little usage of this blood test, which is commercially available at all pathology laboratories costing $26.00.

We also know that if there is a family history of prostate cancer, that is a first degree relative; father, son or brother with prostate cancer and that diagnosis is made around the age of 60, relatives of that prostate cancer sufferer have a three times increased risk for the development of prostate cancer. Unfortunately there is no equivalent test such as the BRCa1 gene testing done in breast cancer high-risk families.

Prostate cancer is diagnosed generally after a PSA blood test is drawn or an abnormal digital rectal examination is found. After appropriate information given to the patient, most organisations such as the Urological Society of Australasia recommend that men between the age of 50 and 70 who have at least ten-year life expectancy be recommended to have a PSA blood test. PSA blood test, whilst not 100% sensitive and 100% specific for prostate cancer diagnosis, is the best marker in oncology. It is also relevant that PSA has a 60% better positive predictive value for cancer diagnosis than does mammographic screening.

A man diagnosed with prostate cancer between the age of 50 and 70 with a ten-year life expectancy almost certainly will die from prostate cancer and not with prostate cancer. A man who has a PSA elevation sees his local doctor and is then recommended to do a biopsy on the prostate under transrectal ultrasound guidance. This is a very accurate way of diagnosing prostate cancer, which is clinically significant. Transrectal ultrasound guided biopsy has about a 90% accuracy of finding clinically significant prostate cancer.

Once a man has had prostate cancer diagnosed and is suitable for curative therapy there are a number of options for him. The mainstay of treatment for organ confined prostate cancer has been radical retropubic prostatectomy. This operation has been refined significantly over the past ten years. The problem of incontinence, which bedevilled this operation in earlier times, has become much less significant. Most centres where this operation is performed now have incontinence rates around 1 to 2%. This incontinence means a total incontinence where some form of artificial sphincter or urinary diversion would be required for control of urinary flow. Minor incontinence like stress incontinence happens in approximately 20% of men who have radical prostatectomy. This is often managed with pelvic floor exercises and no other therapy.

There have also been significant improvements in radiation therapy for organ confined prostate cancer. Outcomes in terms of cure rates for radiation compared to radical prostatectomy are very similar. The event of intensity modulated radiation therapy and conformal radiation therapy techniques means that scatter of the radiation therapy beam is minimised and the prostate is optimally treated for cure. Morbidity from both radiation therapy and surgery relates mainly to sexual dysfunction. Approximately 70% of men after radical prostatectomy will have difficulty obtaining spontaneous erection without pharmacological help. About 60% of men after external beam radiation therapy will also have sexual dysfunction requiring further management. This sexual dysfunction remains the major morbidity from curative therapy for prostate cancer.

Some men who have other co-morbidities where curative therapy is inappropriate will be assigned to a program of watchful waiting using PSA as a clinical measure for disease progression. In these patients often hormonal therapy using injectable LHRH analogues will provide many years of amelioration of prostate cancer.

In summary at present in Australia only one in ten men will have appropriate prostate cancer testing that is digital rectal examination and PSA blood test annually. Although the Federal Department of Health suggests that PSA testing is overdone in our community, most PSA testing is done for disease monitoring rather than for screening diagnosis.

It would be timely to introduce an education and awareness campaign for men in the Australian community and their partners to understand the problem of prostate cancer in our community and allow men to make an informed choice regarding testing and options for curative therapy.

Informed Choice

Rather than an endless unanswerable debate as to whether PSA testing will lower mortality from prostate cancer, we should move to whether it is appropriate for men to be informed regarding prostate cancer. Men need to know the significance of prostate cancer as a health risk, that there is available testing and curative treatments are provided should the man wish to avail himself of this opportunity. As previously stated the European study of screening for prostate cancer will not report until 2007. Around 180,000 men are being randomised. One might well speculate that all of the methodology problems and all of the criticisms of every study published of this nature will occur when the results of this screening program are available. There will be cross over of men from non-screen to screened, there will be drop out and there will be suggestions of bias. I believe it is prudent for us to realise that epidemiology will not necessarily give the answers to fundamental questions regarding prostate cancer screening and mortality.

For example an Australian man of fifty whose father died from prostate cancer must have the knowledge of the extremely high risk for the development of prostate cancer and probable death from prostate cancer if diagnosed and untreated. Most Australian men are unaware of the risk posed by having a family history of prostate cancer. The absence of proof does not mean the absence of common sense. It is important to inform the Australian community of the risk, diagnosis and therapy for prostate cancer

The Myths and prostate cancer

For some time we have heard from opponents of prostate cancer testing that all men have prostate cancer. It is a subclinical non-lethal disease borne out by autopsy findings in elderly men.

Secondly prostate cancer treatment is worse than the disease and it is better not to know you have prostate cancer until you become symptomatic.

It is now proven that autopsy found prostate cancer is a clinically insignificant disease not diagnosed by PSA testing. Autopsy or latent prostate cancer does not raise the level of PSA. Reasonable estimates of incidentally diagnosed prostate cancer rate between 6 and 14% from PSA testing.

The criticism that modern therapy has too high a morbidity and mortality to justify its implementation is extremely misleading. In 1978 a study by the American College of Surgeons showed that 70% of men presenting with prostate cancer had metastatic disease at the time of diagnosis. This is incurable prostate cancer which invariably led to a death from inanition with painful bony metastatic disease. In 2002 after the advent of PSA testing, 20% of men who present with prostate cancer, present with metastatic disease. Modern surgical and radiotherapy techniques have reduced the morbidity for curative treatment for prostate cancer to very low levels. Consumers or patients with prostate cancer or with the potential for the diagnosis of prostate cancer seem to be the most clear in their attitudes to PSA testing. A recent qualitative study published in the British Medical Journal, 2002, found that most men who had or possibly had prostate cancer advocated routine PSA testing because they believe early diagnosis was important for cure and quality of life. Doctors need to understand why people want wider access to PSA so that they can find better ways of communicating information about risk. Only four of the 52 men interviewed in this study opposed to screening because of the uncertainty associated with the benefits.

The questions we should be asking:

Do we see and treat incidental or autopsy found latent prostate cancer?
Does PSA diagnosed prostate cancer offer a lead time to allow potentially curative therapy?
Is the histological type of prostate cancer discovered in the PSA area lethal if untreated?
Do modern curative therapies offer real cure?
Are we offering curative therapies to those men who untreated would die from the disease?
Are we already witnessing a reduction in prostate cancer mortality?

1. Do we see and treat incidental or autopsy found latent prostate cancer?

Prostate cancer has a complex natural history, there is a high prevalence of incidence over clinically expressed prostate cancer. There is a very high prevalence of subclinical or pre-neoplastic latent prostate cancer. Latent prostate cancer is found in 30% of men less than 50 years. Autopsy studies have shown that 25 to 30% of men less than 50 have subclinical foci of prostate cancer. Latent prostate cancer however is universal. There is a small geographic or ethnic variation in incidence. Latent prostate cancer is not detected on PSA screening. The majority of PSA detected prostate cancer is clinically significant. Insignificant prostate cancer, that is Gleason score less than 6 with a volume less than 0.5 ccs is diagnosed at a rate between 3 and 16%. PSA does not detect latent autopsy prostate cancer where the volume of prostate cancer is less than 0.5 ccs. Prostate cancer at this volume does not secrete PSA sufficient to alter normal levels, that is the incidental or autopsy found prostate cancer which has so be-devilled the prostate cancer debate does not produce an elevated PSA and will not be incidentally diagnosed.

2. Does PSA diagnosed prostate cancer offer a lead time to allow potentially curative therapy?

Recent studies including the Physicians Health Study show that PSA diagnosed prostate cancer allows a lead time of 5.5 years in a diagnosis of aggressive or lethal prostate cancer. There has been an at least 50% drop in metastatic rate at diagnosis allowing an earlier staged diagnosis in young men and increases the rate of organ confined cancer. Organ confined cancer is that cancer which can be treated with curative intent by surgery or radiation therapy. PSA diagnosed prostate cancer presents a lower stage cancer in young men. A recent study in the British Journal of Urology entitled ‘Survival prospects after PSA detection of prostate cancer’ concluded that PSA detected prostate cancer allows a mean of nine years before clinical presentation. Clinical presentation of prostate cancer, that is symptomatic prostate cancer relates to symptoms of bladder neck obstruction, haematuria and bone pain from metastatic deposits. This diagnosis equals advanced, local and or metastatic disease. Death will ensue between two and five years.

Prior to 1985 only a few men were examined for prostate cancer, digital rectal examination was the only test and diagnosis of prostate cancer provoked a therapeutic nihilism.

After 1985 with the advent of Prostatic Specific Antigen testing and the ability to clearly image the prostate with transrectal ultrasound enabled very accurate guided biopsy techniques. Anatomical radical prostatectomy techniques were introduced in the United States. This description by Walsh enabled control of the blood supply of the prostate, preservation of continence and in many cases preservation of potency. Since 1985 we have seen a new era in surgery for men with prostate cancer. Modern radiation therapy techniques have also been introduced using narrow fields with better fractionation. Seed implantation with external beam therapy as a boost has also been introduced with a lower morbidity.

3. Is the histological type of prostate cancer discovered in the PSA area lethal if untreated?

Numerous studies have shown that well differentiated prostate cancer does not bring about the death of a host whereas moderate to poorly differentiated prostate cancer that is Gleason 6, 7 and beyond will kill a host if untreated. The majority of patients presenting for curative therapy for prostate cancer have Gleason 6 or 7 mainly 4+3 or 3+4.

There are numerous studies from Johanssen, Albertson, Chodak and Lu Yao, to demonstrate that well differentiated prostate cancer does not require treatment and moderate to poorly differentiated cancer will bring about the death of a man if untreated if his life expectancy is ten years or greater.

In the Lu Yao Study of Prostate Cancer Specific Survival published in 1997 in the Lancet, of 60,000 patients who were stratified as Gleason 2 to 4, Gleason 5 to 7 and Gleason 8 to 10 treated by surgery, radiation or watchful waiting. Those men with high grade prostate cancer died in high numbers without treatment. Patients with Gleason 8 or beyond treated with watchful waiting had a 45% prostate cancer specific survival, where those treated with surgery had 50% greater survival.

Another study published by Albertson in 1998 in JAMA, looked at men treated expectantly demonstrating a 70% mortality of Gleason grade 7 prostate cancer and an 87% prostate cancer mortality in Gleason grade 8 and beyond. Albertson concluded that men with Gleason grade 7 to 10 have a substantial risk of dying from prostate cancer if the cancer is untreated. Albertson also remarked of the profound impact of treatment and survival after diagnosis of high grade prostate cancer.

4. Do modern curative therapies offer real cure?

A number of studies attest the ability of surgery or radiation therapy to cure organ confined high grade prostate cancer. Studies from Scardino 1983 and 1997, Chodak 1994, Gerben 1997, MAYO Clinic 1998 and St Louis 1998 demonstrate survival rates at ten years around 80% and at 15 years 71% for radical curative therapy for men with Gleason grade 7 cancers and above. Finally a study by Catalona, 1998 of PSA detected prostate cancers in 1,778 showed a 96% cancer specific survival at seven years.

In conclusion it appears that data from modern surgical series clearly support the concept that cure is possible for those men with prostate cancer which if untreated would kill than individual. It appears that we can now offer curative therapy to those who truly need it.

5. Are we see offering curative therapies to those men who untreated would die from the disease?

As mentioned in the previous paragraphs, watchful waiting for men with high grade prostate cancer that is Gleason 7 above, it will bring about the death of that patient within ten years.

6. Are we already witnessing a reduction in prostate cancer mortality?

In the United States there has been a 6% fall in prostate cancer mortality between 1990 and 1995. There was a 12% drop in mortality from prostate cancer in men less than 75 years. There was a 1% annual decline in prostate cancer deaths from 1990. The Omstead County Study shows a 22% reduction in prostate cancer mortality between 1980 and 1997.

There has been a similar decline in prostate cancer mortality in Canada. Meyer reports a study in Quebec between 1979 and 1996 which demonstrated an increase in mortality until 1989, a stabilisation in mortality in 1995 and a 15% reduction of mortality in 1998. There has been an overall decline in mortality of 9.6% from prostate cancer between 1991 and 1996 in Quebec most marked in men less than 75 years.

In contrast in Mexico where PSA testing is not performed, there has been an increase in prostate cancer mortality from 3 per 100,000 to 6 per 100,000 between 1980 and 1995.

In Australia the age standardised incidence and mortality from prostate cancer from 1993 to 1998 has shown an interesting trend. In the years 1992 to 1996 there was a dramatic increase in incidence of prostate cancer indicative of PSA screening detecting clinical prostate cancer earlier. There is also a drop in mortality from prostate cancer beyond 1996 which has continued through to year 2000. This may reflect better treatment and also earlier diagnosis providing curative therapy to those men who would have died from prostate cancer without treatment. The NSW cancer registry statistics demonstrated a 21% reduction in prostate cancer death rate in the decade 1990 to 2000.

It is time to move from the angst driven debate regarding prostate cancer screening to discuss the above questions and talk about new paradigm. The morbidity of current curative therapies remains unacceptable either by radiation therapy or surgery although there have been dramatic improvements in reducing morbidity of these therapies. There are now merging therapies such as chemoprevention, early and intermittent hormone therapy, gene and protein expression identification, new drug strategies, anti-sense strategies, all with a role to play in modern prostate cancer treatment. We are entering an exciting era in diagnosis and treatment of this lethal disease. Many men who previously would have died from prostate cancer may be able to live very long and productive lives using strategies to make it a chronic disease rather than a lethal disease.