Prostate Cancer In Ghana And The Wider Black Community: It Is Time To Consider Screening

INTRODUCTION
Prostate cancer (PCa) is the second most frequently diagnosed cancer in the world and the leading cancer affecting men in Ghana. If PCa is identified early in its natural history, it is eminently treatable with great potential for cure. Black men have the highest age standardized PCa-specific mortality rates in the world. Why is this so and what can be done to reduce the morbidity and mortality associated with PCa in Ghanaian men.

Prostate cancer has a variable natural history ranging from slowly growing indolent cancers at one end of the spectrum to aggressive cancers with high Gleason scores at the other end. Early disease is usually asymptomatic but detectable by screening methods. To date, most cancers in Ghana are identified after symptoms appear. This paper examines the role of screening and argues for increased screening in the population.

Keywords: Ghanaian Men, prostate cancer, screening
High rates of PCa have been reported in several Black men territories and PCa may rightly be considered a major health problem in most of these countries. Of greater concern is the recent report by Prostate Cancer UK indicating that black men have the highest risk factor for prostate cancer? In the Caribbean's, Jamaica, the local cancer registry which records all cancers diagnosed in the Kingston and St Andrew area reports that the age-standardized PCa incidence for the period 2003-2007 was 78. 1/100 000/ year (2) making it by far the leading cancer affecting men in Jamaica. Significantly, PCa is also the leading cause of male cancer-related deaths in Jamaica at 53. 9/100 000/year (4). In the French territory, Guadeloupe, PCa incidence has recently been reported at 168/100000/year (5) and in Tobago, a high prevalence of screen-detected PCa three times that typically seen in Caucasian populations has been reported (6). Prostate cancer is also three times more common in Afro-Trinidadians compared to Indo-Trinidadians (7). In Barbados, incidence and mortality rates for PCa are high at 160. 4/100 000/year and 63. 2/100 000/year respectively, using the United States (US) population as standard (7).

The high incidence of PCa amongst Afro-Carib-bean men is also seen in emigrants to the United Kingdom (UK) and their descendants with incidence rates being three times higher in these men compared to Caucasians in the UK (8).

Despite the increasing use of prostate specific antigen (PSA) in Ghana with no policy regarding prostate cancer screening in Ghana as practiced in the UK , The prostate cancer risk management program(PCRMP). In Jamaica, approximately 50% of men with newly diagnosed PCa in Kingston and St Andrew are still discovered on the basis of symptoms and signs and therefore present with locally advanced and metastatic disease with its attendant morbidity and mortality. Indeed, no appreciable downward stage migration has been observed in Jamaica as was experienced over a decade ago in the United States of America (USA) with widespread use of PSA as a screening tool.

While PCa does not discriminate between men of different socio-economic positions, its impact upon men and their families from the lowest socio-economic stratum is especially devastating. These men are the ones most likely to present with advanced and incurable disease through lack of awareness and inaccessibility to early detection. Advanced PCa presents a significant care giving, emotional and financial burden to the families of these mostly middle-aged and elderly men. Given that increasing age is a risk factor for PCa, the ageing of Ghanaian men populations is likely to be accompanied by an increasing prevalence of PCa and a corresponding increase in the financial and care giving burden to families given the cancer's relatively long natural history. There is also the financial burden to the already fragile and resource-limited health sectors of the developing countries of the black men. The costs incurred in treating advanced disease and castration-resistant PCa and its resultant complications are known to outstrip the costs involved in the early detection and treatment of organ-confined disease. Management of advanced disease usually involves recurring costs for expensive drugs as well as frequent clinic and hospital visits, typically for the remainder of the patient's lifetime. In the terminal phase of the disease, significant costs are incurred in the rendering of palliative treatments which may involve expensive interventional radiological, urological and radiotherapy interventions.

SCREENING
Screening is used to discover clinically significant disease early in the disease process to prevent mortality and morbidity through treatment and has become widely accepted in healthcare. There are several success stories. Mammography for breast cancer and Papanicolau smears for cervical cancer are examples of population screening while antenatal screening and faecal blood for colon cancer are examples of successful "high risk" screening. Not all screening programmes are without debate, however, and PCa screening has engendered significant debate and controversy over the years. Opponents of PCa screening argue that there has not been unequivocal evidence of net benefits over harm and that there is a significant risk of over-detection and over-treatment of tumours that would not have caused morbidity or death. Proponents argue that screening can identify men who need treatment and reduce the burden of disease. Surveys done in North America reveal that most primary care physicians favour prostate screening. Programs for men over 50years are available for men in the UK under auspices of the NHS Prostate Cancer Risk Management Program (PCRMP).

The Prostate Cancer Risk Management Programme ensures that men requesting a prostate-specific antigen (PSA) test are provided with information about the benefits, limitations and risks to enable them to make an informed choice. The PCRMP is also responsible for improving the quality of PSA testing, for the quality of processes in the diagnosis of prostate cancer and for providing a systematic and standardized follow up pathway as far as the point of diagnosis.

These guidelines for transrectal ultrasound guided biopsy of the prostate were developed in association with the Department of Pathology, University of Liverpool. In addition, a systematic review was commissioned by the Centre for Reviews and Dissemination, University of York, to evaluate systematic prostate biopsy methods in the investigation for prostate cancer.

Early detection programmes for PCa exist in Jamaica through the work of the Jamaica Cancer Society in collaboration with the Jamaica Urological Society. Men 40 years and older with at least a 10-15-year life expectancy are encouraged to have an annual digital rectal examination (DRE) and PSA blood test. Very few men, however, seem to heed this call. A recent study by Morris of 2000 Jamaican men over 55 years revealed that only 35% of them had done a prostate check (Morris, 2009 - Personal communication). Forty-one per cent of the men reported that the reason for this was that they had not been advised by their doctors to have one done.

Health behavior in general is gender related with women being more likely than men to practice health-promoting behaviors. Seeking healthcare is viewed by men to be associated with femininity while illness is associated with weakness and vulnerability. These gender differences in health-seeking behavior is exemplified by statistics on screening from the Jamaica Cancer Society indicating that in 2009 whereas 13 168 women presented for mammography and pap smears, only 464 men presented for prostate cancer screening in the corresponding period (personal communication).

Other significant barriers exist to accessing prostate cancer screening by Jamaican men. Research is required in this area but these barriers probably include cultural views and expectations of manhood, poverty, ignorance, apathy, fatalism, stoicism, denial of risk, difficulty accessing preventive care, and specific issues related to the digital rectal examination (DRE). Many men resist having the DRE possibly due to its cultural unacceptability and existing taboos regarding anal penetration of whatever kind. However, reluctance to have the DRE is not unique to Jamaican men as African-Canadian men have been noted to avoid the DRE due to the perceived association with homosexuality.

There is ignorance surrounding the best application of the tests used in the early detection of PCa amongst the local medical profession. For example, men with limited life expectancy, by virtue of age or co-morbid illness, who would not benefit from early detection and treatment of PCa are commonly screened for the disease by general practitioners. Also, general practitioners continue to send men suspected of having PCa to have a transrectal ultrasound without a concomitant prostate biopsy in the mistaken belief that the ultrasound alone may accurately exclude PCa. There is also ignorance regarding the variety of treatments available commensurate with the stage of the disease and their potential side-effects. Also pre-sent are special interest groups promoting their own preventive or curative fix for PCa without any basis in robust medical evidence. These persons add to the already high levels of ignorance, myth and speculation regarding the disease by promoting half-truths and unproven treatments. A fully informed, educated and aware public is the best antidote for this.

Is screening effective? Retrospective analysis of the Prostate Cancer Risk Management Programme (PCRMP) UK.

There is no organised screening programme for prostate cancer in the UK but an informed choice programme called Prostate Cancer Risk Management, has been introduced.

Why isn't there a national screening programme for prostate cancer?

All screening programmes cause some harm. This could include false alarms, inducing anxiety, and the treatment of early disease which would not otherwise have become a problem.

When considering population screening programmes the benefits and harms must be carefully assessed, and the benefits should always outweigh the harms.

Until there is clear evidence to show that a national screening programme will bring more benefit than harm, the NHS will not be inviting men who have no symptoms for prostate cancer screening.

In 1968, Wilson and Jungner of the World Health Organisation developed ten principles which should govern a national screening programme. These are:

The condition is an important health problem
Its natural history is well understood
It is recognisable at an early stage
Treatment is better at an early stage
A suitable test exists
An acceptable test exists
Adequate facilities exist to cope with abnormalities detected

Screening is done at repeated intervals when the onset is insidious

The chance of harm is less than the chance of benefit

The cost is balanced against benefit
To date, prostate cancer screening fulfils only the first condition. See the Health Technology Assessment Programme's monograph Diagnosis, management and screening of early localised prostate cancer: a review for details.

Evidence from a prostate cancer screening trial in Europe, ERSPC, has shown that screening reduced mortality by 20 per cent. However, this was associated with a high level of over treatment. To save one life, 48 additional cases of prostate cancer needed to be treated.

Following research evidence published in 1997 the UK National Screening Committee recommended that a prostate cancer screening programme should not be introduced in England. This policy was reviewed in Dec 2010 but no significant changes were made. It is due to be considered again in 2013/14, or earlier if significant new evidence emerges.

Although evidence does not yet support population screening for prostate cancer there is considerable demand for the PSA test amongst men worried about the disease. In response to this, the Prostate Cancer Risk Management programme was introduced in September 2002.

The PCRM provides high quality information to enable men to decide whether or not to have the PSA test based on the available evidence about risks and benefits. After consideration of this information and in discussion with their GPs, men over 50 who choose to have the test may do so free of charge, on the NHS.

The informed medical practitioner and lay public alike may be confused by the ongoing controversy within the international medical community regarding screening for prostate cancer. This confusion stems from the question of whether prostate cancer screening achieves its stated objective of reducing prostate cancer-specific mortality whilst minimizing the potential for harm amongst screened individuals in robust randomized controlled trials (RCTs). A reduction in cancer- specific mortality in a well conducted RCT is the 'acid test' of a cancer screening programme's efficacy. These experimental studies eliminate well-known biases and confounding variables, particularly those that specifically arise during observational studies on screening. These are lead-time bias, length bias, and the healthy volunteer bias, inter alia. The first refers to an apparent increase in length of survival of screened individuals that simply results from diagnosing the tumour at an earlier stage in its natural history, the second refers to the apparent improvement in survival that accrues from diagnosing a greater proportion of more slowly growing tumours in screen-detected cancers, the last arises from the higher proportion of healthier persons amongst those usually volunteering for screening compared to persons with routinely detected clinical cancers.

The results of three other RCTs of prostate cancer screening have been released since the initial two in 2009. One of these, the Goteburg trial, demonstrated a clear benefit to screening with screened men enjoying a 50% reduction in mortality . In this trial, 293 men needed to be screened and 12 men treated in order to prevent one death from the disease. On the contrary, a population-based trial from Sweden with more than 20 years of follow-up data did not demonstrate a benefit to screening . One criticism of the latter study is that men were screened by DRE only for a significant period of the trial. The third trial with 15 years follow-up, published in 2011, demonstrated a benefit to screening. The controversy rages on.

A consensus view on the early detection of prostate cancer, led by experts at the Prostate Cancer World Congress, Melbourne, 7–10thAugust 2013

Recent guideline statements and recommendations have led to further confusion and controversy regarding the use of Prostate Specific Antigen (PSA) testing for the early detection of prostate cancer. Despite high-level evidence for the use of PSA testing as a screening tool, and also for its role as a predictor of future risk, the U.S. Preventive Services Taskforce (USPSTF) has called for PSA testing to be abandoned completely , and many men are therefore not given the opportunity for shared decision-making. Other groups such as the American Urological Association, National Comprehensive Cancer Network, and European Association of Urology support a role for PSA screening but with somewhat conflicting recommendations. The majority of guideline statements have endorsed the role of shared decision-making for men considering PSA testing.

To address these somewhat conflicting and confusing positions, a group of leading prostate cancer experts from around the world have come together at the 2013 Prostate Cancer World Congress in Melbourne and have generated the following set of consensus statements regarding the use of PSA testing. The goal of these statements is to bring some clarity to the confusion that exists with existing guidelines, and to present reasonable and rational guidance for the early detection of prostate cancer today.

1. Consensus Statement 1: For men aged 50–69, level 1 evidence demonstrates that PSA testing reduces prostate cancer-specific mortality and the incidence of metastatic prostate cancer. In the European Randomized Study of Screening for Prostate Cancer (ERSPC), screening reduced metastatic disease and prostate cancer-specific mortality by up to 30% and 21% respectively in the intent-to-treat analysis, with a greater reduction after adjustment for noncompliance and contamination. In addition, the Goteborg randomized population-based randomized trial showed a reduction in metastatic disease and prostate cancer mortality with screening starting at age 50 . The degree of over-diagnosis and over-treatment reduces considerably with longer follow-up, such that the numbers needed to screen and numbers needed to diagnose compare very favourably with screening for breast cancer. While routine population-based screening is not recommended, healthy, well-informed men in this age group should be fully counseled about the positive and negative aspects of PSA testing to reduce their risk of metastases and death. This should be part of a shared decision-making process.

2. Consensus Statement 2: Prostate cancer diagnosis must be uncoupled from prostate cancer intervention. Although screening is essential to diagnose high-risk cases within the window of curability, it is clear that many men with low-risk prostate cancer do not need aggressive treatment. Active surveillance protocols have been developed and have been shown to be a reasonable and safe option for many men with low-volume, low-risk prostate cancer . While it is accepted that active surveillance does not address the issue of over-diagnosis, it does provide a vehicle to avoid excessive intervention. Active surveillance strategies need standardization and validation internationally to reassure patients and clinicians that this is a safe strategy.

3. Consensus Statement 3: PSA testing should not be considered on its own, but rather as part of a multivariable approach to early prostate cancer detection. PSA is a weak predictor of current risk and additional variables such as digital rectal examination, prostate volume, family history, ethnicity, risk prediction models, and new tools such as the phi test, can help to better risk stratify men. Prostate cancer risk calculators such as those generated from the ERSPC ROTTERDAM (www.prostatecancer-riskcalculator.com), the Prostate Cancer Prevention Trial (PCPT) (http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp), and from Canada (prostaterisk.ca), are useful tools to help men understand the risk of prostate cancer in these populations. Further developments in the area of biomarkers, as well as improvements in imaging will continue to improve risk stratification, with potential for reduction in over-diagnosis and over-treatment of lower risk disease.

4. Consensus Statement 4: Baseline PSA testing for men in their 40s is useful for predicting the future risk of prostate cancer. Although these men were not included in the two main randomized trials, there is strong evidence that this is a group of men who may benefit from the use of PSA testing as a baseline to aid risk stratification for their likely future risk for developing prostate cancer , including clinically significant prostate cancer. Studies have shown the value of PSA testing in this cohort for predicting the increased likelihood of developing prostate cancer 25 years later for men whose baseline PSA is in the highest centiles above the median . For example, those men with a PSA below the median could be spared regular PSA testing as their future risk of developing prostate cancer is comparatively low, whereas those with a PSA above the median are at considerably higher risk and need closer surveillance. The median PSA for men aged 40–49 ranges from 0.5–0.7 ng/ml, with the 75th percentile ranging from 0.7–0.9ng/ml. The higher above the median, the greater the risk of later developing life-threatening disease. We recommend that a baseline PSA in the 40s has value for risk stratification and this option should be discussed with men in this age group as part of a shared decision-making process.

5. Consensus Statement 5: Older men in good health with over ten year life expectancy should not be denied PSA testing on the basis of their age. Men should be assessed on an individual basis rather than applying an arbitrary chronological age beyond which testing should not occur. As life expectancy improves in many countries around the world (men aged 70 in Australia have a 15 year life expectancy), a small proportion of older men may benefit from an early diagnosis of more aggressive forms of localised prostate cancer, just as it is clear that men with many competing co-morbidities and less aggressive forms of prostate cancer are unlikely to benefit irrespective of age. Likewise, a man in his 70s who has had a stable PSA at or below the median for a number of years previously is at low risk of developing a threatening prostate cancer and regular PSA screening should be discouraged.

An important goal when considering early detection of prostate cancer today, is to maintain the gains that have been made in survival over the past thirty years since the introduction of PSA testing, while minimizing the harms associated with over-diagnosis and over-treatment. This is already happening in Australia where over 40% of patients with low-risk prostate cancer are managed with surveillance or watchful waiting , and in Sweden where 59% of very low risk patients are on active surveillance. This is also reflected in current guidelines from the EAU, NCCN and other expert bodies, and in a comment from AUA Guideline author Dr Bal Carter in the BJU International.

Abandonment of PSA testing as recommended by the USPSTF, would lead to a large increase in men presenting with advanced prostate cancer and a reversal of the gains made in prostate cancer mortality over the past three decades.

However, any discussion about surveillance is predicated on having a diagnosis of early prostate cancer in the first instance. As Dr Joseph Smith editorialized in the Journal of Urology following the publication of the ERSPC and PLCO trials, “treatment or non-treatment decisions can be made once a cancer is found, but not knowing about it in the first place surely burns bridges” A key strategy therefore is to continue to offer well-informed men the opportunity to be diagnosed early, while minimizing harms by avoiding intervention in those men at low risk of disease progression. This consensus statement provides some guidance to help achieve these goals.

Should Ghanaian men screen for prostate cancer?
Based on what is currently known, can prostate cancer screening be recommended for the Ghanaian men? Would it positively impact upon the health of Ghanaian men people and would it be a feasible and cost-effective intervention? Would it also be able to compete with other health interventions for the limited funding for healthcare that is available? The authors do not pretend to be able to answer these questions but given the high prostate cancer mortality rates in the black community like Ghana and the ageing of the populations, I believe that it is time for the relevant authorities in the Ghana and black territories to consider this issue. The criteria which should be satisfied for implementing a screening programme as suggested by Junger and Wilson in 1968 should serve as a guide in considering this potentially contentious issue. Ghana also needs the prostate cancer risk management program (PCRMP) as practiced in the UK and the Melbourne Consensus guidelines on Prostate cancer Screening.

The criterion that the disease be an important health problem is readily satisfied by the high mortality rates in the Ghana and black community. Its natural history is reasonably well-known and it has a clear preclinical phase which is identifiable through the use of the tumour marker PSA. The operating characteristics of PSA are well-known and favorable towards cancer detection. On weighing the available evidence relating to the efficacy of PSA-based prostate cancer screening, one could infer that there would be a net benefit to screening in reducing prostate cancer specific mortality in high risk Black populations. The screening tests are relatively inexpensive and the PSA test is acceptable to men although cultural resistance to the DRE exists. There exist sufficient resources and personnel for follow-up and treatment of identified disease, at least in some Caribbean territories where there are enough trained urologists. However, more radiation and clinical oncologists are needed, particularly for some high risk cancers where a multidisciplinary approach is favored. On the downside, over-detection and over-treatment of clinically insignificant cancers in screened men with the potential for net harm over benefit is a real possibility as suggested by the ERSPC.

It is time for the Ministries of Health; Ghana Health Service in Ghana to seriously consider doing feasibility studies on PCa screening as something urgently needs to be done to stem the comparatively high mortality rate affecting Ghanaian men from this common disease.

Conclusion :
Prostate cancer is a serious health problem in Ghana and the black community with high incidence and mortality rates affecting a predominantly Black population. Research is required to help elucidate the importance of locally relevant modifiable risk factors so that preventive strategies may be instituted both at the population and individual levels. Also, effective secondary preventive strategies such as mass screening and other interventions should be urgently considered to bring this common disease under control and reduce not only the mortality but the morbidity and accompanying caregiver burden. Ghana currently needs a policy on prostate cancer screening for men over 35years as soon as possible.

REFERENCES
D Murphy .The Melbourne (Aug 7, 2013)Consensus Statement of Prostate Cancer Screening www.bjuinternational.com/.../the-melbourne-consensus-statement-on-pro.

2. PCRMP Guide No 1-NHS Cancer Screening Programmes. www.cancerscreening.nhs.uk/prostate/pcrmp-guide-1.html‎.

WD Aiken; D Eldemire-Shearer (2012). Prostate cancer in Jamaica and the wider Caribbean: it is time to consider screening. West Indian Medical Journal.vol.61 no.1 Mona