THE purpose of screening is to identify pre-clinical and asymptomatic cases of a disease in a population at risk as opposed to making a diagnosis based on a patient’s presentation with symptoms and disease.
“The use of the Prostate-Specific Antigen (PSA) test and a Digital Rectal Examination (DRE) to screen for prostate cancer and whether such use can reduce prostate cancer specific mortality has universally been regarded as controversial despite the publication of more than 1000 articles in the medical and scientific literature,” said Dr Richard Ablin the discoverer of the prostate-specific antigen (PSA) in his recent visit to Tanzania.
Dr Ablin led to the development of the PSA test widely used today as the principal diagnostic tool for prostate cancer. He is also a pioneer of cryosurgery and the use of cryoimmunotherapy for the treatment of cancer, and has extensive experience in cancer research, particularly in the study of the development and metastasis of cancer.
He is also a Diplomate of the American Board of Clinical Immunology & Allergy and is Certified by the American Academy of Microbiology in Public Health and Medical Laboratory Microbiology, and is a member of numerous professional societies.
The Prostate, Lung, Colorectal and Ovarian (PLCO) trial, started in 1993 in the United States, and the European Randomized Study of Screening for Prostate Cancer (ERSPC), started in 1994, respectively enrolled nearly 77,000 and 182,000 men randomly assigned to receive screening or not.
The PLCO trial three found no difference in mortality from combined screening with the PSA test and DRE through 10 years; the ERSPC trial four reported that PSA screening without DRE was associated through nine years with a 20 per cent reduction in mortality from prostate cancer.
Parenthetically, it is of interest to note that, in the absence of the inclusion of a DRE as part of their screening protocol, the ERSPC trial did not follow the FDA-approval guidelines, which state that the PSA test “was approved for use in conjunction with a DRE”.
In the face of the facts and the interim results of the PLCO and ERSPC trials, organizations that remain in support of screening for prostate cancer, particularly the American Urological Association, whose president, John Barry, has stated that “PSA testing for prostate cancer remains a valuable screening tool and should be appropriately offered to men,” need to re-examine the dictum Primum non nocere: “First do no harm.”
The controversy about PSA screening is continuing in spite of recently released early reports of two large prostate cancer-screening studies thus creating a great need to advise patients despite such a controversy.
Prostate cancer is the most common cancer in men and therefore an important issue. The autopsy detection rates are very high, with approximately 40 per cent of autopsies of men aged 50 years having evidence of prostate cancer and with 80 per cent of autopsies of 90-year-old men showing evidence of prostate cancer. It is widely known that generally prostate cancer may grow very slowly and never cause symptoms. Also, deaths from prostate cancer occur mainly in older men.
In order to assess the role of PSA and screening for prostate cancer, one should review the WHO criteria for population-based screening. The principles articulated by the WHO states that, the test should be suitable and that means accurate, acceptable, safe, and relatively inexpensive.
There should be an agreed policy on whom to treat as patients, and there should be facilities for diagnosis and effective treatment. An organized screening programme should be implemented only if there is good evidence of reduced cancer specific mortality and a population that will benefit can be achieved with appropriate balance of benefits and harms.
The European study showed a 20 per cent reduction in prostate cancer death from screening at four-year intervals whereas the American PLCO study of annual screening showed a non-significant increase in the prostate cancer death rate.
Some experts believe that expansion of PSA screening beyond the current informal position is not justified and, indeed, may produce harm. However, there is insufficient evidence to this present opportunistic PSA screening practice.
How can we, therefore, advise men of whether to undergo screening or not?
Information about prostate cancer screening is best discussed with the primary care physician. The primary care physician is in a good position to determine the relative importance of a possible prostate cancer diagnosis in the context of an individual patient and can advise against screening, for example, when life expectancy is less than 10 years. The primary care physician can also carry out DRE, which, although not a good screening method, would exclude advanced cancer.
Most urologists submit that symptomatic men should be investigated appropriately even though symptoms of frequency or nocturia (the need to get up during the night in order to urinate, thus interrupting sleep) are not cancer-specific symptoms and are not usually associated with prostate cancer until relatively advanced disease.
Men who are unfit for curative intervention should not be screened and men who are unwilling to accept curative treatment if cancers were found should not be screened. It is accepted that screening is not appropriate when the estimated life expectancy is less than 10 years because the patient is unlikely to live long enough to benefit from treatment.
Those who support PSA screening generally recommend testing for men between the ages of 50 and 70. Some have advocated screening younger men, for example, between the ages of 45 to 50, especially if in high-risk group. High-risk groups include those patients with family history of prostate cancer.
The potential harms of prostate screening that need to be communicated to patients include false positive or false negative PSA test outcomes and potential failure of PSA screening to detect all cancers, although it generally detects those most likely to cause death. The potential morbidity from diagnostic investigations such as prostate biopsies and potential physical and psychological adverse effects from treatment must be explained to the patient.
It is important to note that patients with PSA screen detected cancer are usually suited for several treatments. It is important for them to be educated about the relative benefits of radical prostatectomy, radiation therapy, and active surveillance.
Active surveillance is a selection of patients with probably indolent cancer for periodic monitoring by means of PSA testing and periodic re-biopsy. It is advised, on active surveillance, that treatment and intervention is recommended if PSA doubling rate is faster than three years and if the repeat biopsy shows increased grade of cancer or if the patient chooses to undergo active treatment.
At the present time, there are a number of ongoing trials of active surveillance and the current result show that half of the suitable patients can delay treatment for 5 to 8 years with coexistent reduction in side effects. It is expected that active surveillance will not decrease survival. Although many experts see active surveillance as a solution to the burden of over-treatment, there is no current level one evidence (i.e. Evidence obtained from at least one properly designed randomized trial) that outcomes of active surveillance are equivalent to those of immediate treatment.
Early stage prostate cancer is associated with prolonged survival even if cancer is not cured. As well,
our approaches to the PSA detected early stage prostate cancer continue to evolve. Modern treatments are associated with less morbidity than in the past.
Therefore, 15-30 years may elapse before the relative risks and benefits of the population-based screening programmes will be fully appreciated. In the meantime, patients and caregivers need to be informed about the pros and cons of screening intervention and make individual decisions based on their own circumstances and preferences.
In Tanzania, the 50 plus campaign was initiated by the Center for Human Rights Promotion (CHRP) with the primary goal of the campaign which is to reduce the sufferings and deaths caused by prostate cancer.
That is being achieved through education, awareness, dissemination of information on the disease; encourage check-up; extend support, care, treatment and capacity building. As health is a human right issue, the campaign implementation will be a right based approach.
“I am a prostate cancer survivor. The first cancer cell started to develop in my prostate at the age of about 51 (1997). Even though I had a habit to do medical check-up yearly, no doctor asked or suggested to me to do a prostate cancer screening,”says Dr Emmanuel Kandusi who is the Campaign Coordinator of Tanzania 50 Plus Campaign.
He adds: “And even in 2007 when I started getting warning signs such painful and burning sensation when urinating, the doctor ordered for a routine check-up just to be cleared NAD. Of course prostate cancer cannot be detected through urine routine check-ups! It wasn’t until sometime July 2008 when things went to the worse that the doctor ordered for a PSA test which gave a score 100ng/ml (normal is 0-4 ng/ml).”
“The team of doctors in Indraprastha Apollo Hospital, New Delhi, India found the PSA score was 4517 ng/ml and an advanced adenocarcinoma (cancer) of the prostate Gleason’s Grade 8 (4+4). Thus they suggested two therapies - surgery or hormone therapy by injection. I opted for surgery. After surgery I am now under medication taking one Bicalutamide Tablet 50 gm daily. I wish my prostate cancer was discovered early. The Chinese proverb says, ‘To know the road ahead, ask those coming back’. I am the one coming back and so share my experience”.