more_vertJeremy Hunt, UK health secretary, has assertively announced plans to impose consultant contracts that dictate consultant presence in hospitals 24 h a day, 7 days a week (24/7).1 The Royal College of Obstetricians and Gynaecologists, in its report High Quality Women’s Health Care: A Proposal for Change, has also recommended 168 h of consultant presence per week in maternity units with more than 6000 births per year.2
Preference: Men's Health
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[Correspondence] Mobilising the Campaign to End Fistula
In 2004, the United Nations Population Fund (UNFPA) and its partners launched the Campaign to End Fistula, yet how much has changed for women’s health since its conception? Overall, improvements in women’s health would appear positive; as maternal and child mortality rates have halved in the past two decades, a successful foundation has been established for the Sustainable Development Goals (SDG).1 This is a remarkable achievement for many developing countries in view of the rise in population size, declining rates in income growth, and increasing political instability.
The global challenge of women’s health
Sierra Leone, a West African state of 6 million, saw 11 000 cases and over 3000 deaths during last year’s Ebola outbreak. A bitter civil war from 1991 to 2002, fuelled largely by fierce factions from neighbouring countries, led to 50 000 deaths and degradation of the country’s infrastructure and social fabric. Sierra Leone’s exports of diamonds and bauxite notwithstanding, the lack of a socially responsive polity and a largely agrarian population set the scene for the epidemic. Over 70% of its population live in extreme poverty.1
Sierra Leone also tops the 2013 chart when it comes to maternal deaths — 1100 per 100 000 live births.2 The comparable figure for Australia is six. UNICEF estimates that 88% of the women have been subject to genital mutilation.3
Improving maternal health
The Millennium Development Goals, promulgated by the United Nations in September 2000 and endorsed by 189 countries, sought to halve desperate poverty, defined as living on less than a dollar a day, by 2015. The metrics suggest that this goal has been achieved, and it is a remarkable tribute to international efforts. Among the eight goals, five concern health, and most have been achieved, including huge reductions in infant mortality.
Improving maternal health is one of the health-related goals that has proved harder to reach. Under Goal 5, countries committed to reducing maternal mortality by three-quarters between 1990 and 2015. Since 1990, maternal deaths worldwide have dropped by 45%.4
Maternal mortality — often due to blood loss and infection — has proved more resistant to efforts to substantially reduce it as a global health problem. It has been intractable in areas of poverty and social turmoil. There were 289 000 maternal deaths worldwide reported in 2013.4
The explanation for these disturbing figures has much to do with social attitudes and investment. When we encounter health disparities, the explanation is most often found outside the clinic, in society and politics. In preventing maternal death, strong investment in education for women is fundamental. Provision of the basic infrastructure necessary for safe childbirth comes next. But even more basic is a pathological view of women — that they are not a priority and that public resources should be invested elsewhere.
Broadening the focus
The World Health Organization draws our attention in 2015 to food security. Its importance is great for women’s health, before and during reproduction and throughout all adulthood, to reduce the risk of nutritional deficiencies, diabetes and heart disease.
When, in 2003–2004, my colleagues at Columbia University and I were examining cardiovascular disease in emerging economies, I was amazed to discover that it far outweighed obstetric and perinatal disorders, HIV and malaria as causes of death of women in the years of family formation and support. In seven out of nine developing countries that we studied, chronic diseases caused over 20% of deaths among women aged 15–34 years, while reproductive causes and HIV together accounted for about 10% of deaths.5 We questioned why the traditional conceptualisation of women’s health has more to do with disorders that impair their performance as reproductive machines than with the real threats to their wellbeing, including the precursors of cardiovascular catastrophe. Those who work on global programs to abate the scourge of diabetes make a major contribution to reducing deaths among women from cardiovascular disease.
Shaking stereotypic thinking
Even if our view of women’s health is restricted to an understanding of causes of death, it is clear we have a task to shake the stereotypic thinking and social relegation of women that foster a completely inadequate global response to their health needs.
There are tasks aplenty for those with advocacy in their blood at governmental, educational and individual levels. Heroic clinicians such as 91-year-old Dr Catherine Hamlin AC and her co-workers at the Addis Ababa Fistula Hospital, its five regional hospitals and the Hamlin College of Midwives set outstanding examples of other pathways.
Medically assisted circumcision: a safer option for initiation rites
Culturally sensitive integration of medical circumcision could avert adverse effects at traditional male initiation rites
In many traditional cultures, male initiation rites involve circumcision practices that can sometimes result in medical complications. In a recent incident in the Northern Territory, three young men required airlifting from their Borroloola initiation site to Darwin for medical assistance.1 The risk of permanent harm and potentially fatal outcomes could be decreased if safer options were available during initiation ceremonies. In this article, we report that it is possible to provide safe circumcision at male initiation rites.
In December 2013, a traditional initiation ceremony was conducted in Drekikier District, East Sepik Province, Papua New Guinea (PNG). During the 4-week ceremony, circumcision, considered vital for transition from boyhood to manhood, is conducted in the first week. Previously, young initiates suffered excruciating pain and severe blood loss when a carved cassowary bone was used to cut the penis and foreskin. On this occasion, at the invitation of community leaders, a medical team assembled at the site to provide safe male circumcision for 34 initiates.
The team consisted of a medical officer, two community health workers, an HIV counsellor and the provincial HIV response coordinator. Consistent with local cultural traditions, the entire team consisted of men originating from the local cultural group who also participated in cleansing rituals as part of the ceremony. Medical supplies, surgical instruments and a portable steriliser were brought to the initiation site deep in the forest. A specially built traditional dwelling stood in the middle of a small clearing. The few bush tracks that led into the site were carefully concealed to be completely segregated from other villagers, especially women and children.
A small shelter that stood immediately to the back of and continuous with the main ceremony house served as the operating theatre. It had an opening in the roof to allow sunlight in. Two beds and two tables were assembled in the centre of this structure. The beds served as operating tables and the tables were used for medical supplies and surgical instruments. The medical officer and one community health worker performed complete foreskin removals with assistance from other team members. Five to 10 mL of 1% lignocaine was infiltrated around the base of the penis and the procedure was conducted using sterile technique.
Five or six circumcisions were performed per day. Of the 32 initiates who were circumcised, only two experienced adverse events. The first had slight bleeding, rectified by reinforcing the gauze bandage and gentle continuous pressure for 1 minute. The second experienced heightened pain despite having two 500 mg paracetamol tablets after the procedure. This pain resolved after further regular doses of paracetamol.
Two initiates had previous penile modifications and were refused surgery. The injection of substances (such as cooking oil) or insertion of objects (such as ball bearings) under the skin of the penis can cause extensive scarring and disfigurement.2,3 For the safety of the initiates with previous penile modifications, arrangements were made for their circumcision to be done in the district hospital.
A number of challenges were encountered. Health workers needed to be re-deployed from existing programs and some supervisors were reluctant to allow staff to participate. Surgical instruments and medical supplies were sourced from provincial health facilities and were provided with a degree of reluctance. The makeshift operating theatre did not have a good light source, nor was it enclosed by flywire to keep insects out. Sterilisation was challenging, with forceps and tissue scissors washed in water collected from a nearby stream, placed in kidney dishes and sterilised in a pressurised portable steriliser heated over a fire for 30 minutes. This took 1 hour and limited the number of procedures per day.
Despite these challenges, the service proved successful. Of the 32 initiates circumcised, all had successful healing and fully participated in the remaining activities, including instruction on responsible living, family planning, wealth acquisition and respect for one another. All initiates completed the 4-week ceremony with a rousing celebration on 15 January 2014.
Improving the evidence base and increasing the availability of safe male circumcision procedures was a major recommendation from a recent national policy forum in PNG.4,5 Providing safe circumcision at the initiation site meant that some aspects of traditional circumcision were adjusted. Circumcision was delegated and performed entirely by the medical team, albeit a team of local cultural origin. Penile foreskins were completely removed, and medically contraindicated procedures such as urethral poking or scarification were not performed. However, chants and recitals continued in the main ceremony house as initiates were being circumcised.
This experience has shown that it is possible to provide medically assisted circumcision within initiation ceremonies in cultures that traditionally practise male circumcision in PNG. A similar approach may assist cultural groups in Australia to reduce the risk of adverse effects from male circumcision during traditional initiation ceremonies.
Engaging Aboriginal and Torres Strait Islander men in primary care settings
To the Editor: It is well recognised that Aboriginal and Torres Strait Islander men are one of the most disadvantaged population groups in Australia in terms of physical wellbeing.1 Annual Medicare Benefits Schedule health assessment items are essential tools to help Aboriginal and Torres Strait Islander men (and women and children) receive primary health care matched to their needs, as well as opportunities for preventive health care and education.
A growing body of evidence suggests that erectile dysfunction (ED) coexists with, or is a clinical marker for, other common life-threatening conditions, such as coronary heart disease and type 2 diabetes, due to shared underlying neurovascular mechanisms.2 Indeed, the relative risk and severity of coronary artery disease appears to be higher for young men reporting ED.3 Despite this, discussion with Aboriginal and Torres Strait Islander men about sexual health is often lacking. In such population groups at risk of chronic disease, the opportunity to assess erectile function may present a window of opportunity to identify and better manage life-threatening disease.2
To engage these men in sexual health discussions, a greater focus on culturally appropriate health services is needed. Cultural competency training is essential to overcome the barriers affecting how Aboriginal and Torres Strait Islander men access health services (Box 1). However, the sex-specific nature of some barriers and the impact of traditional and cultural roles on health service access pathways for men often require further attention, particularly for more culturally sensitive issues such as sexual health.
There are many other strategies and practical approaches that health services and primary health care professionals can implement to better engage Aboriginal and Torres Strait Islander men in positive and broader help-seeking behaviour and health service access (Box 2).6 Being able to implement such strategies may be an indirect reflection on the ability of health services to support cultural respect and provide culturally safe health care more broadly.
1 Factors influencing health service access and help-seeking behaviour for Aboriginal and Torres Strait Islander men4,5
Societal
- Illness-related stigma
- Sex-specific differences in health
Cultural
- Traditional gender-related law, masculinity and gender roles
- Language barriers
- Beliefs around causation
Logistical
- Lack of transport
- Conflict of appointment times with other family and community priorities (eg, ceremonies)
Health system
- Limited access to specialist services and/or treatment
- Complicated referral process
- Too few (male) health professionals, leading to patients seeing many different doctors
- Medical terminology and jargon
Financial
- Difficulties in meeting health service costs
Individual
- Knowledge or perception of the nature of the illness
- Previous illness experience
- Low prioritisation of preventive health care
- Lack of understanding and embarrassment
- Low self-esteem and confidence
2 Examples of culturally appropriate strategies for engaging with Aboriginal and Torres Strait Islander men about sexual health issues
- Provide a safe, private and comfortable environment that supports open and free dialogue
- Men may not open up in the first consultation — take time to build trust and respect
- Encourage men to have annual health assessments and incorporate sexual health questioning into these
- Make the clinic conducive to talking about sensitive issues; for example, a model of the male pelvis in the consulting room might help initiate discussion
- If only female health care providers are available, approach gender-specific issues in a sensitive way and use male Aboriginal health workers for advice or, if not urgent, refer to a male general practitioner
Risk assessment to guide prostate cancer screening decisions: a cost-effectiveness analysis
Correction
Error in calculating costs of screening: In “Risk assessment to guide prostate cancer screening decisions: a cost-effectiveness analysis” in the 3 June 2013 issue of the Journal (Med J Aust 2013; 198: 546-550), there was an error in the way screening costs were calculated. These corrections do not alter the study conclusions. The corrected figures are in bold as follows.
Results section of the abstract (page 546): “The base-case incremental cost effectiveness ratio of PSA screening was $168 611 per QALY for men with average risk, $73 452 per QALY for men with two times the average risk, and $22 938 per QALY for men with five times the average risk.”
First paragraph of the results section (page 547): “For men with an average risk, PSA screening led to an additional 2.7 quality-adjusted life-days (14.3 undiscounted) at an additional cost of $1263, giving an incremental cost effectiveness ratio (ICER) of $168 611 per QALY gained. For the high-risk cohort, PSA screening led to an additional 8.3 quality-adjusted life-days (43.0 undiscounted) at an additional cost of $1671, giving an ICER of $73 452 per QALY gained. For the very high-risk cohort, PSA screening led to an additional 32.9 quality adjusted life-days (161.2 undiscounted) at an additional cost of $2067, giving an ICER of $22 938 per QALY gained . . .”.
Second paragraph of the discussion section (page 549): “We estimated that for a 50-year-old man with average risk, PSA screening would lead to an average additional $1263 per individual screened, with negligible increase in quality-adjusted survival. The cost-effectiveness of screening remained unfavourable for the high-risk cohort at $73 452 per QALY gained, but was considerably more attractive for the very high-risk group at $22 938 per QALY gained.”
Are bald men more virile than their well thatched contemporaries?
The suggestion that bald men are more virile than their well-thatched contemporaries is probably an old wives’ tale, but it must be conceded that old wives are likely to be unusually authoritative in this matter.1
John Burton and colleagues were the first to examine the contentious view that an association exists between virility and baldness in 1979. Notably Burton himself was balding at this time. However, the hypothesis has never been directly tested. In Burton et al’s study of 48 men aged 35–64 years, surrogate markers of “masculinity” such as hair density on the trunk and limbs, serum testosterone levels, sebum secretion rate, sweat secretion rate, skin thickness, muscle thickness and bone thickness showed no relationship to baldness.1 Virility per se was not assessed. Factors suggestive of a possible association include the lack of balding among eunuchs2 and pseudohermaphrodites,3 indicating that testosterone and its biologically active metabolite dihydrotestosterone are prerequisites for common baldness.4 Furthermore, the principal side effect of treatment of male pattern baldness with finasteride (a compound that prevents the conversion of testosterone to dihydrotestosterone) is loss of libido and erectile dysfunction;5 and oral antiandrogen therapy is not used to treat androgenetic alopecia in men, as it has a profound inhibitory effect on the male libido, evidenced by its use to deliberately reduce sex drive in the treatment of deviant sexual behaviour in men.
Methods
In order to resolve this vexing question, we used data from a study originally designed to examine risk factors for prostate cancer.6 This study was conducted in Australia between 1994 and 1997 in men under 70 years of age. Men with prostate cancer were recruited from cancer registers, and unaffected controls were recruited from electoral registers. All subjects were interviewed in person and were categorised into four patterns of baldness (nil, receding only, vertex only and fully bald) by the interviewer (Box 1). At the end of the interview, in private, subjects completed a questionnaire that elicited not only their history of ejaculations obtained by any means between the ages of 20 and 49 years but also their number of sexual partners.
Ethics approval for the use of the data in this study was obtained from cancer registry human research ethics committees in Victoria, New South Wales and Western Australia.
Results
There were 2836 men who took part in the original study. Information on sexual function and sexual partners was available for 2205 men. We performed a secondary analysis of risk factors for baldness using unconditional logistic regression with baldness as the outcome and adjusting for age. As there were no differences in associations between baldness and virility in men with and without prostate cancer, we combined the data (Box 2).
No significant association was found between baldness (either limited to vertex balding at the crown or being fully bald) and the frequency of ejaculations between age 20 and 49 years (Box 2), but bald men were significantly less likely to have had more than four female sexual partners in their lifetime.
Discussion
For our null findings to be explained by selection bias, we would have to postulate that relatively fewer virile bald men than non-virile bald men participated. Given that virility was not mentioned in any of the study information, and that virile men are likely to be participatory, this seems unlikely. Similarly, for reporting bias to have explained the null finding, would require that the virile bald men underreported the frequency of their ejaculations and non-virile men overreported. At the time the study was conducted, the myth that bald men are more virile was widespread, so we think it more likely that all participants would err on the side of societal expectations and overreport.
In the population we studied, bald men appear to be no more virile than their well thatched contemporaries. On the contrary, they seem to have fewer conquests. Although old wives may not be as authoritative on this matter as was once thought, it may be that bald men have earned this plaudit by being more faithful to them.
1 Examples of androgenetic alopecia patterns in men*
* Categorised in this study as (l to r) “nil”, “receding only”, “vertex only” and “fully bald”.
2 Risk of baldness and men’s average frequency of ejaculations between 20 and 49 years of age and their number of female sexual partners
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Baldness |
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Not bald* |
Bald† |
Odds ratio (95% CI) |
P‡ |
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Weekly average ejaculations |
n = 532 |
n = 1673 |
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0.55 |
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Up to average 2.3 times a week |
113 (21%) |
398 (24%) |
1.00 |
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Average 2.3–3.3 times a week |
118 (22%) |
330 (20%) |
0.86 (0.63–1.16) |
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Average 3.3–4.7 times a week |
110 (21%) |
350 (21%) |
0.99 (0.73–1.34) |
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Average 4.7–7 times a week |
103 (19%) |
341 (20%) |
1.08 (0.79–1.48) |
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More than 7 times a week |
88 (17%) |
254 (15%) |
0.90 (0.65–1.24) |
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Number of female sexual partners |
n = 520 |
n = 1625 |
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< 0.001 |
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0–1 |
128 (25%) |
549 (34%) |
1.00 |
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2–4 |
58 (11%) |
221 (14%) |
0.90 (0.63–1.28) |
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5–14 |
118 (23%) |
318 (20%) |
0.71 (0.53–0.95) |
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15–29 |
100 (19%) |
245 (15%) |
0.68 (0.50–0.92) |
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30+ |
116 (22%) |
292 (18%) |
0.69 (0.51–0.92) |
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* Recorded by the interviewer as either “nil” or “receding only”. † Recorded by the interviewer as either “vertex only” or “fully bald”. ‡ P < 0.05 significant. |
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Should we screen for prostate cancer? A re-examination of the evidence
The potential harms from diagnosis, overdiagnosis and treatment must not be overlooked
Despite the results of two large, but conflicting, trials published side by side in 2009, whether prostate cancer screening is beneficial or harmful (or indeterminate) remains unresolved.1,2 Those on either side of the debate read the same information but interpret it differently, declaring that it supports their unchanged positions.
That prostate cancer is important is not at issue: it is the ninth-ranked cause of disease burden in men in Australia, representing the loss of 36 000 disability-adjusted life-years (DALYs), or 2.7% of the total Australian loss, in 2003.3 This is about two-thirds of the loss resulting from breast cancer in women (60 000 DALYs; 4.8%). A positive family history of prostate cancer is associated with increased risk (typically a risk ratio of about 2),4 although this risk may be exaggerated by detection bias (men with a positive family history are more likely to have a screening test).5 Associations with family history of other conditions are less certain.5
The rate of prostate-specific antigen (PSA) testing is high enough to represent a de facto screening program (in the same order as breast screening). It has increased from about 200/1000 per year (age standardised) in the 1995–96 financial year to more than 400/1000 in 2010–11, although it may now be declining, following the United States Preventive Services Task Force recommendations to stop screening for prostate cancer.6–8 The rate of radical prostatectomy among men aged 50 years or older in Australia has increased in line with this from less than
1/1000 in the 1995–96 financial year to more than 2.5/1000 per year in 2007–08.8 Tumour size and age at prostatectomy have decreased in the US.9 But mortality from prostate cancer has changed little in Australia in 20 years, decreasing overall from 0.6/1000 in 1985 to just under 0.5/1000 in 2007.8 The even greater surge in screening among men aged 50 years or older in the US, from 35% in 1987 to 90% in 1992, has meant that symptomatic presentation of localised prostate cancer has dropped from 77% to 60% over the same period.10
Why is prostate cancer screening so difficult?
PSA, a protease that breaks down the ejaculate coagulum in mammalian species, is a weak test for prostate cancer.11 Its protein is highly specific for prostatic tissue, both benign and malignant, so it is useful in identifying prostate tissue in tumours of uncertain origin.12 However, PSA in the blood is detected in patients with a wide variety of benign and malignant disorders, and also increases normally with age, making it difficult to develop useful reference ranges to predict prostate volume.13 The test characteristics of PSA testing (sensitivity and specificity) are uncertain because determining prevalence requires histological testing. Indirect evidence suggests that it is a poor screening test; a German study found the total PSA level of 131 men with benign prostate hypertrophy could not be distinguished from that of 79 men with localised prostate cancer suitable for radical prostatectomy.14 US studies show that PSA testing contributes little to the diagnosis of early prostate cancer.9 It may be better at ruling out prostate cancer, although the optimal PSA cut-point is uncertain.
The search to find better screening markers has produced other tests, such as measuring the ratio of free PSA to total PSA (which is little better14), and following the change in PSA levels over time to determine the rate of increase in PSA (which requires multiple testing).
While the PSA blood test can potentially detect some early, low-volume and localised prostate cancer, allowing its eradication by radical prostatectomy,15 digital rectal examination (DRE) occasionally detects some of the cancers missed by PSA testing alone, which is why those recommending PSA screening advocate DRE as well.15
Are there benefits of screening?
Men with negative results on the screening test will be reassured (although sometimes falsely). Two large RCTs were published in 2009 looking at the effects on mortality in men with positive results on PSA testing. A US trial found no benefit,1 while a European trial found a small statistically significant reduction in mortality.2 A subsequent report from one centre (Gothenburg, Sweden) within the European trial, which followed the study cohort for 12 years, found a greater reduction in mortality, which increased after a decade.16 Nevertheless, two systematic reviews including all reported trial data concluded that screening is not effective.17,18
The trials described in the systematic reviews may be criticised for deficiencies in compliance — the US trial in particular was compromised because about half of the control group of men undertook some screening,1 while conversely, in the European studies, some men assigned to the screening group did not receive screening.2
We attempted to perform a correction for compliance, which suggested that after correction, a relative risk reduction of death from prostate cancer from being screened is still not statistically significant at 12% (95% CI, − 1% to 23%) (Box).22
What are the downsides of screening?
Downsides of treatment
After radical prostatectomy, erectile dysfunction affects most men — fewer among younger men, those with a lower PSA level and perhaps those undergoing special nerve-sparing surgical techniques.23 Other complications are common too, including urinary incontinence (which is very common in the months after treatment, returning to normal in 75%–90% of men after 2 years, depending on surgical technique) and, with less frequency, urinary irritation and bowel symptoms.24 General feelings of “vitality” are lost in about 10% of men.25
Harms from diagnosis
Prostatic biopsy after abnormal PSA or DRE results may cause severe bleeding and infection (about 1% each). One-quarter of the 1% admitted with infection after biopsy require intensive care treatment for severe sepsis.26
The rates of suicide and cardiovascular disease (CVD) increase enormously immediately after men are given a diagnosis of prostate cancer (a retrospective cohort study in Sweden found that the relative risk of suicide increased eight times, and the risk of CVD increased 11 times).25 These risks level off after 1 week, but remain high for years afterwards.27
Related to this problem is the issue of lag-time, which is the time between diagnosis by screening and the time when the cancer would have become manifest symptomatically without screening. Lag-time yields benefit if it allows a cancer to be cured by radical surgery. But it causes harm also, because it means patients live longer under the cloud of the diagnosis of a malignancy, with the harmful effects mentioned above. Lag-time has been estimated to be as long as 11 years.28
Harms from overdiagnosis
It is said that “More men die with prostate cancer than from it”.29 However this is difficult to quantify because of the variation in the threshold for men submitting themselves for prostate cancer testing. The best available data come from autopsy studies of men dying from other causes whose prostates have been examined histologically. The literature is confused by different histological definitions of prostate cancer, but at least one well conducted study suggests that rates of latent prostate cancer are as high as more than 50% in men aged over 60 years — so that it might even be called “normal” at that age,27 and a review of data from several countries confirms this.30 In other words, only a minority of cancers lead to symptoms and mortality. Latent cancers are indolent (“lazy”) cancers that look like, but do not behave like, metastasising ones. Unfortunately we can only poorly distinguish them histologically using relatively crude methods such as the Gleason score. The consequence is overdiagnosis. The more we test for prostate cancer, the more we will detect it, harvesting more and more latent cancers whose effects would never have become manifest — leaving only the adverse effects of diagnosis and treatment on the harms–benefits scale. Modelling studies using data from results of recent trials suggest that as many as 50% of detected prostate cancers are overdiagnosed latent tumours.28
A response to this is the emerging management option of “active surveillance”, in which cancers with a better prognosis are initially managed conservatively.
How should patients be informed?
Should clinicians raise the topic . . .
Before ordering a PSA test? Although all authorities agree that informed consent should be obtained before ordering a PSA test, these are often ordered without any discussion at all,31,32 and when discussions do occur, they are often unbalanced, with the pros of screening emphasised more than the cons.33
When not ordering a PSA test? Most authorities have proposed that clinicians should raise the topic of prostate cancer screening with all men as part of general disease prevention and health promotion, provide relevant information, and then together with the patient make an informed decision about prostate cancer screening. However, the information is difficult to present and process. Moreover the media, and some well publicised charities, often portray the debate confusingly, over-simplifying the issues so that the takeaway message is often that prostate screening is beneficial. In particular, it is difficult to justify raising this form of prevention, which is not accepted as effective, over the legion of others that are. A more justifiable approach is to avoid raising prostate cancer screening unless a patient does. When it is raised, it should be discussed in a balanced manner with the relevant information given.
What information can clinicians provide?
Decision aids present balanced information and help patients to participate in decision making. They can improve knowledge, increase patients’ desire to be more actively involved in decision making, decrease interest in PSA testing, and decrease PSA testing rates in patients as part of routine care (if not among those men specifically seeking screening). Such aids include videotapes, written materials or educational sessions.34 They can be computer-based and interactive (eg, http://www.prosdex.com).35
However, decision aids alone are not enough. They should supplement discussions between patient and doctor — before, during and/or after. Most decision aids do not appropriately consider patients with low health literacy, and patients often find them too long — even interactive online decision aids, where patients need to invest only about 20 minutes.36,37
When patients raise the topic of prostate cancer screening, a clinician might initially discuss the main issues — the uncertainty of benefit, and the potential harms as well as the potential benefits. It is important for patients to digest these issues before further discussions, perhaps using a decision aid.
Not rushing the decision is important. In primary care it is usually possible to suggest that patients take away information to consider, perhaps in conjunction with their family, before taking a blood test slip to the laboratory.
Results of meta-analysis of five randomised controlled trials (RCTs) of screening for prostate cancer, adjusted for adherence to the screening protocol
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Stockholm19 |
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Quebec20 |
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Norrköping21 |
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PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial)1 |
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ERSPC (European Randomized Study of Screening for Prostate Cancer)2 |
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RRR = relative risk reduction. * Adherence data are not available for the Stockholm and Norrköping trials. † Meta-analysis combining the data (giving a non-significant RRR of 8.6% of deaths from prostate cancer). § Meta-analysis adjusted for degree of adherence to screening that may have influenced the trials (giving a relative non-significant reduction of 12% of deaths from prostate cancer). |
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Patterns of care for men diagnosed with prostate cancer in Victoria from 2008Â to 2011
The Victorian Cancer Registry estimates that the number of men diagnosed with cancer will increase by 75% in the next 10 years, largely due to prostate cancer — the most common cancer diagnosis in men.1 Algorithms have been developed to calculate risk of prostate cancer progression at time of diagnosis for men with localised disease, classifying men into four groups: very low, low, intermediate and high risk of recurrence (Appendix 1).2,3 The National Comprehensive Cancer Network (NCCN) guidelines suggest that many men with very low-risk clinically localised disease should be managed with active surveillance; men with low-risk and intermediate-risk disease should be managed with active surveillance or with external beam radiation therapy (EBRT), radical prostatectomy (RP), brachytherapy, or a combination of these treatments; and men with high-risk disease should be managed with EBRT and androgen deprivation therapy (ADT), or EBRT, high dose rate brachytherapy and ADT, or RP and pelvic node dissection.2
Few studies have compared the effectiveness of treatments for localised disease.4 The recently published Prostate Cancer Intervention Versus Observation Trial (PIVOT) — a randomised control trial comparing RP with watchful waiting in 731 US patients with localised prostate cancer disease — showed that RP was associated with reduced all-cause mortality for men with a prostate-specific antigen (PSA) level greater than 10 ng/mL but that it offered no survival benefit to men with a PSA level of 10 ng/mL or less.5 A systematic review comparing disease-free survival for low dose rate brachytherapy with other treatments for men with clinically localised prostate cancer found no significant difference when compared with RP.6
Little is known about current patterns of care for men diagnosed with prostate cancer in Australia and whether treatment correlates with clinical practice guidelines. A population-based patterns-of-care survey conducted in Victoria in 1993 showed that 11% of men diagnosed with prostate cancer had received the diagnosis following informal screening and 25% received definitive curative therapy.7 New South Wales data show that the annual number of PSA tests performed more than doubled, from 184 350 tests in 1996 to 433 187 in 2006.8 The impact that this has had on patterns of care is unknown.
Our aim was to use the Prostate Cancer Registry to assess patterns of care for men diagnosed with prostate cancer at contributing hospitals in Victoria.
Methods
The Prostate Cancer Registry was established as a rapid case-ascertainment registry in 2009 to monitor patterns and quality of care for Victorian men diagnosed with prostate cancer. Details of the registry, including methods for data collection, are described elsewhere.9 Initially, four hospitals (three metropolitan, one regional) contributed data, accounting for about 25% of all Victorian patients with newly diagnosed prostate cancer (calculated based on 2009 incident notification data supplied to the Victorian Cancer Registry). Addition of 13 hospitals in 2010 increased capture to about 75% of newly diagnosed patients in Victoria. With Human Research Ethics Committee approval from the hospitals that contributed data to the Prostate Cancer Registry, prostate cancer notifications that were submitted by these hospitals to the Victorian Cancer Registry are also forwarded to the Prostate Cancer Registry.
Inclusion and exclusion criteria
Men were included in the study if they had been diagnosed with prostate cancer between August 2008 and February 2011 — confirmed pathologically or by a bone, magnetic resonance imaging or computed tomography scan — and were notified to the Prostate Cancer Registry after the date on which the relevant hospital began contributing data. Consent was obtained from clinicians to include patients in the Prostate Cancer Registry. Clinicians were asked to advise the Prostate Cancer Registry if they felt it inappropriate for a patient to be included in the study — for example, for mental health reasons.
Recruitment
An explanatory statement, available in 12 common languages, was sent to men who were eligible to participate in the study about 9 months after they had been diagnosed. The statement invited them to participate in the Prostate Cancer Registry and provided an opt-out option.
Data collection
Histopathological data were captured through hospital information systems and pathology reports. Clinical information — including PSA level at diagnosis and procedure type (including approach) — was captured from medical records by trained data collectors before patients were interviewed over the telephone about their quality of life and to confirm treatment details 12 months after diagnosis. Periodically, hospitals are asked to validate biopsy and radical prostatectomy operations against International Classification of Diseases (10th revision) codes to confirm complete capture of prostate cancer cases by the Prostate Cancer Registry. Treatments provided within 12 months of diagnosis were included in the analysis.
Statistical analysis
Frequencies were used to describe treatment modalities and risk groups, using NCCN risk of disease progression categories (Appendix 1). While the NCCN includes a very low-risk category, this could not be calculated because the Prostate Cancer Registry does not collect PSA density, which is a required parameter in the calculation for very low risk. The Gleason score documented in the histopathology report at the time of biopsy was used in the NCCN algorithm. Where no clinical T stage was recorded but the Gleason score was ≤ 6 and PSA level was < 10 ng/mL, the patient was classified as having disease that was at low risk of progression. Patients were categorised as having no active treatment if their clinical records recorded “active surveillance” or “watchful waiting” and also if there was no documentation of active surveillance or watchful waiting but no treatment was delivered in the within 12 months of diagnosis.
A Pearson’s χ2 test was used to compare the association between presence of treatment within 12 months of diagnosis and categorical predictor variables of age at diagnosis, risk of disease progression at diagnosis and type of hospital and hospital location attended at diagnosis. These variables were then included in a multivariate logistic regression model. To compare categorical data for the 2008–2011 cohort with 1993 data,7 a two-sided Fisher exact test was used. Stata/IC 11.0 (StataCorp) was used for all analyses and a two-sided P value < 0.05 was considered to be statistically significant.
Results
The recruitment of patients for the study is summarised in Box 1. A total of 3268 notifications were received before 1 February 2012 by the Prostate Cancer Registry for the period August 2008 to February 2011. In total, 492 men (15.1%) were ineligible. Of the 2776 who were eligible and for whom treatment data were sought, 52 (1.9%) did not provide consent for participation, leaving 2724 men (98.1%) for whom treatment data were collected and follow-up data were sought. As 697 men were lost to follow-up, confirmation of treatment and PSA levels were obtained for 2027 of the eligible men who provided consent for participation (74.4%).
Hospital and patient characteristics
Hospital characteristics and patient characteristics at time of diagnosis are shown in Box 2. Notifications from 11 public and six private hospitals were progressively added to the Prostate Cancer Registry. Most patients were diagnosed at metropolitan hospitals, and there were similar numbers of patients from public hospitals and private hospitals. Mean age at diagnosis was 66.2 years (SD, 8.9 years; range, 46.5–96.6 years). Median PSA level at diagnosis was 6.8 ng/mL (interquartile range, 4.7–10.6 ng/mL; range, 0.7–57 ng/mL). A PSA level of ≤ 4.0 ng/mL is considered normal. Most patients (92.9% [2531/2724]) were classified as having clinically localised disease, almost half were classified as being at intermediate risk of disease progression (44.1% [1201/2724]), and intermediate-risk disease affected almost half (47.5% [1201/2531]) of those who had clinically localised disease.
Treatment details
The principal treatment types according to risk of disease progression are summarised in Box 3. Nearly half of men with clinically localised disease (46.1% [1168/2531]) had RP, and more than half of those with intermediate risk of disease progression (54.5% [655/1201]) had RP. Of the 1195 men who had RP, 780 (65.3%) had open RP, 239 (20.0%) had robot-assisted laparoscopic RP, 88 (7.4%) had laparoscopic RP, five (0.4%) had laparoscopic RP converted to open RP and for 83 (6.9%) approach was not known. For patients with clinically localised disease, there was no significant association between disease risk category and surgical approach (P = 0.47). In total, 558 men (20.5% of those for whom treatment data were collected) were recorded as having received ADT. While 163 men received ADT alone, it was prescribed as an adjuvant or salvage therapy for men receiving EBRT (259), EBRT and high dose rate brachytherapy (60), RP and EBRT (30), RP alone (38), and with high dose rate brachytherapy, low dose rate brachytherapy or chemotherapy (8). Overall, 71.0% of men (1933/2724) received surgery, radiotherapy and/or brachytherapy, and 25.6% of men (698/2724) had EBRT. A notable proportion of those with high-risk localised disease (12.1% [72/594]) received no active treatment, and 40.6% of those with low risk of progression (299/736) received no active treatment.
Frequencies of the categories of age at diagnosis, risk of disease progression at diagnosis and type and location of hospital that provided the prostate cancer notification for men who received active treatment within 12 months of diagnosis and those who did not are shown in Box 4. Results of multivariate logistic regression analysis are shown in Box 5. When men with locally advanced disease were excluded from the model, having a prostate cancer notification made by a private hospital remained an independent factor associated with not receiving treatment (odds ratio, 1.39; 95% CI, 1.12–1.72). When only men with low-risk disease were included in the model, the odds ratio increased to 1.42 (95% CI, 1.16–1.75).
Men who were interviewed at 12 months to confirm treatment details were more likely than those lost to follow-up to have undergone RP alone (40.5% [817/2016] v 32.4% [226/697], P < 0.001), to have had a prostate cancer notification made by a private hospital (53.7% [1082/2016] v 38.3% [267/697], P < 0.001) and to have intermediate risk of disease progression (46.0% [927/2016] v 39.3% [274/697], P < 0.001). They were less likely to have received no active treatment (20.1% [405/2016] v 30.7% [214/697], P < 0.001) and to have locally advanced disease (2.5% [51/2016] v 5.6% [39/697], P < 0.001).
Mortality
There were 24 deaths (from all causes) in the period between diagnosis and follow-up — 13 deaths in the very high-risk (locally advanced) and metastatic disease category, seven in the clinically localised high-risk category, two in the clinically localised low-risk category and two in the clinically localised intermediate-risk category. There was no significant difference in all-cause mortality according to type of hospital that made the notification (1.2% public [16/1374] v 0.6% private [8/1350], P = 0.11) or location of hospital that made the notification (0.9% metropolitan [24/2631] v 0 regional [0/93], P = 0.36).
Patterns of care in 2008–2011 compared with 1993
A comparison of the patterns of care for 2008–2011 and for 1993 is shown in Appendix 2. Median PSA level at diagnosis declined from 20.1 ng/mL in 1993 to 6.8 ng/mL in 2008–2011, and the proportion of men receiving no active treatment declined from 35.6% (373/1048) in 1993 to 22.7% (619/2724) in 2008–2011.7
Discussion
Using Prostate Cancer Registry notifications, we documented patterns of care for Victorian men diagnosed with prostate cancer between August 2008 and February 2011 by collecting treatment data on 98.1% of those who were eligible to participate in the study and interviewing three-quarters of them at 12 months after diagnosis. Intermediate risk of disease progression was the most common NCCN risk category at diagnosis. Within 12 months of diagnosis, nearly half of men with localised disease had RP but more than one-tenth of those with high-risk localised disease had received no active treatment.
Men aged over 75 years were more than 10 times as likely not to receive active treatment compared with those younger than 55 years. Men for whom notifications of prostate cancer were made by private hospitals were significantly less likely to receive active treatment compared with those for whom notifications were made by public hospitals, and men with low-risk localised disease were significantly less likely to receive active treatment compared with men in all other risk categories. The likelihood of not receiving active treatment was inversely related to risk of disease progression.
From 1993 to 2008–2011, there were notable declines in the median PSA level at diagnosis and the percentage of men receiving no active treatment. However, this comparison is based on different methods of data collection — treatment for men in the 1993 study was determined by surveying the treating clinicians 3 years after diagnosis, whereas our 2008–2011 treatment data were collected 12 months after diagnosis. The proportion of men who had no active treatment in our study (22.7%) is similar to that in a US Medicare-linked study (about 23% for men diagnosed in 2007)10 and a South Australian study monitoring men treated in the public health system (about 20% of men diagnosed from 1998 to 2007).11 Men with low-risk disease in our study were four times more likely to receive no treatment compared with men with low-risk disease in 40 urology practices in the United States and recruited to the Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) registry (40.6% v 9%).12 This suggests that there is less overtreatment of patients with low-risk disease in Victoria compared with the US.
Our finding that almost half of men with clinically localised disease had RP is similar to the 50% rate of RP described for men recruited to the CAPSURE registry.12 In contrast, much lower rates have been reported elsewhere: 12%–16% in US Medicare-linked reviews (which captured only men older than 64 years and those with a disability or end-stage renal disease),10,13 11% in a population-based dataset from Northern England,14 23% in the study of men in South Australia who were treated in the public health system,11 and 13% in the previous study of men in Victoria.7
Our finding that 71.0% of men received surgery, radiotherapy and/or brachytherapy contrasts with results of the 1993 Victorian study, in which 25% of men received initial treatment with curative intent.7 Extrapolating this to statewide data using the Victorian Cancer Registry15 would equate to a sevenfold increase in the number of men having RP, from about 280 in 19937 to 2180 in 2010. Similarly, the proportion of men treated with EBRT and high dose rate brachytherapy has increased from 12.0% to 25.6%, or from about 230 men7 to 1370 men over the same period. In future, we expect that the proportion of men receiving robot-assisted laparoscopic RP (20.0% of those who had RP in our study) will increase, as the Prostate Cancer Registry did not receive notifications from facilities performing robot-assisted laparoscopic RP before December 2010.
We identified a sixfold decline in hormonal therapy as front-line treatment for prostate cancer compared with the 1993 Victorian study (38.8% to 6.0%).7 This downward trend was also reported in the South Australian study, although it was less pronounced (OR, 0.58 [95% CI, 0.40–0.82] for men diagnosed between 2004 and 2006 compared with those diagnosed between 1998 and 2000).11
The apparent change in patterns of prostate cancer management in Victoria is consistent with results of studies undertaken in Queensland16 and New South Wales.17 In contrast, the institutionally based South Australian registry shows a consistent proportion of men treated with RP (23% over the 1998–2007 study period), or possibly a slight decline.11
We found that the probability of receiving treatment declined as men aged and as the likelihood of disease progression increased, which is consistent with previous findings.7,12 Of particular interest was our finding that having a prostate cancer notification made by a private hospital was an independent factor for not receiving radical treatment, even after age and of risk of disease progression were taken into account. This contrasts the results of a US study, which showed that having private health insurance was associated with higher rates of treatment compared with not having private health insurance.18
A number of limitations affect the interpretation of our findings. While treatment data were collected for more than 98% of the eligible population, the sample was heavily biased towards men diagnosed and treated at metropolitan hospitals. In addition, hospitals were accrued progressively over the study period, which meant that treatment and outcomes from hospitals that contributed notifications from earlier in the study period were overrepresented. We were unable to interview a quarter of the men diagnosed with prostate cancer 12 months after diagnosis, including all those from non-English speaking backgrounds. This may have resulted in an underestimate of the number of men receiving active treatment and an overestimate of those on active surveillance or watchful waiting. We compared our findings with those from a 1993 patterns-of-care study that collected treatment data over a 3-year period. If our study was extended to include treatment data over a 3-year period, it is likely that an even higher percentage of men would have received active treatment, which would have made the difference between our study and the 1993 study even more pronounced. Another important limitation is that we did not seek to identify reasons why men received no treatment within 12 months of diagnosis. It may be that they were receiving active surveillance, had decided not to pursue active curative treatment, were awaiting therapy on the basis of their PSA level taken at 12 months, or were inadequately managed. Finally, the Prostate Cancer Registry did not collect cause of death, so some deaths may have been unrelated to prostate cancer disease.
The proportion of men receiving treatment with curative intent has increased substantially since 1993. There has also been a dramatic “stage migration” towards earlier diagnosis of prostate cancer — the vast majority of men in our study were diagnosed with localised disease and only 3.3% were diagnosed with metastatic disease. The Prostate Cancer Registry enables rapid and reliable ascertainment of such data on patterns and quality of care for men diagnosed with prostate cancer and reports patterns-of-care and quality indicator data back to clinicians who have contributed more than 20 cases to the registry via quarterly reports.
1 Recruitment of patients for the study
* Patients were interviewed to administer quality-of-life tools (no results of this are included in this article) and to confirm the treatment details that had been collected by data collectors. † Notification of cancer by the hospital was made more than 12 months after diagnosis.
2 Hospital characteristics and patient characteristics at diagnosis of prostate cancer (n = 2724)
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* National Comprehensive Cancer Network risk categories determined taking into account prostate-specific antigen level, Gleason score and clinical stage.7 |
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3 Frequency of principal treatment types according to risk of disease progression* at diagnosis (n = 2724)
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External beam radiation therapy and high dose rate brachytherapy |
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External beam radiation therapy and androgen deprivation therapy |
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* National Comprehensive Cancer Network risk categories determined taking into account prostate-specific antigen level, Gleason score and clinical stage.7 |
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4 Age at diagnosis, risk of disease progression and type and location of hospital that made the prostate cancer notification for men who received active treatment within 12 months of diagnosis and those who did not (n = 2724)
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* National Comprehensive Cancer Network risk categories determined taking into account prostate-specific antigen level, Gleason score and clinical stage.7 |
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5 Results of multivariate logistic regression analysis of factors associated with men not receiving active treatment within 12 months of diagnosis (n = 2724)
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* Reference category. † National Comprehensive Cancer Network risk categories determined taking into account prostate-specific antigen level, Gleason score and clinical stage.7 |
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Risk assessment to guide prostate cancer screening decisions: a cost-effectiveness analysis
Prostate cancer screening using the prostate-specific antigen (PSA) test has been available to asymptomatic men in Australia since the late 1980s; however, substantial uncertainty still remains over the net benefit of early detection.
Based on the trial evidence available to date,1 routine PSA screening for asymptomatic men is not recommended in Australia;2 however, access to PSA testing is available and publically subsidised in Australia through the Medicare Benefits Schedule. The Royal Australian College of General Practitioners (RACGP) recommends that general practitioners assist men seeking PSA screening to reach informed decisions by weighing the potential benefits of screening against the inconvenience and harms of biopsies resulting from false-positive PSA test results, as well as the side effects of unnecessary surgery and/or radiotherapy for indolent cancers that currently cannot be reliably distinguished from those of a more aggressive nature.2
While debate continues about the interpretation of existing trial data in decisions about the PSA screening of asymptomatic men in general, there is a recognition that the trade-off between the potential benefits, harms and financial costs associated with PSA screening may theoretically be more favourable for a subgroup of asymptomatic men who are at elevated risk of prostate cancer.3–5 One reason for this is that the positive predictive value (PPV) of a test is greater in high-risk populations, because PPV is a function of not only the test’s sensitivity and specificity but also of the prevalence of the condition of interest in the population tested. Another reason is that the absolute benefit of an effective intervention tends to be greater for high-risk patients.6
No randomised controlled trials (RCTs) have been completed in asymptomatic high-risk men to inform the size of the possible benefits and harms of PSA screening. Observational studies of screening in higher risk groups have not provided definitive evidence about these trade-offs.5 Statistical modelling techniques have been used to provide valuable insights about the likely impact of PSA screening on quality of life (QOL) and cost-effectiveness;7,8 however, few studies have examined the trade-off between benefits and harms for high-risk populations.3,4 Recently updated outcome data from the largest of the PSA screening trials provide an opportunity to improve our understanding of this trade-off as a function of baseline risk through statistical modelling.9
An improved estimate of the potential net clinical impact and cost of using PSA screening in populations with varying levels of risk is particularly relevant given the discovery of molecular markers that may help classify prostate cancer risk. Risk assessment tools that include these markers appear capable of identifying men with a two to five times increased risk compared with the average.10–12 PSA screening in the subgroup of asymptomatic men at very high risk (ie, five times above the average) and those at high risk (two times above the average) may confer an appreciable net benefit in terms of quality-adjusted survival time and be cost-effective.
The aim of this study was to use the most recent evidence from RCTs of PSA screening to explore the potential value of using risk assessments to guide the use of PSA screening in practice.
Methods
A decision model that incorporated a Markov process was developed using TreeAge Pro 2009 (TreeAge Software Inc) to estimate the lifetime net benefit and cost of PSA screening versus no screening in a simulated cohort of 50-year-old men. Markov processes were used to model the experience of patients as a progression through a series of discrete health states over a time horizon divided into periods, or cycles, of equal duration. Transition probabilities determined the chance of moving from one health state to another at the conclusion of each cycle. Each health state was assigned a QOL utility weighting (on a scale from 0 to 1) and a cost for health care provision over the cycle. The expected cumulative quality-adjusted survival time and financial costs accrued over the entire process were estimated by summing the health gains and costs incurred over all cycles. The effect on the conclusions of varying the parameter estimates included in the model was explored in sensitivity analyses.
A Markov process employing a 1-year cycle length was constructed to model the policy of PSA screening every 4 years against the policy of no PSA screening (Box 1). The transition probabilities used in the model are summarised in Box 2, together with the ranges applied in the sensitivity analyses.
The model made a distinction between prostate cancers that were detected by screening tests (screen-detected) and those that were not detected by screening tests (non-screen-detected). The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial were used to estimate the incidence of both types of prostate cancer.9 Incidence rates were age-adjusted based on Australian age-specific incidence figures. We assumed a PSA test sensitivity of 44% and specificity of 92% at a 4 ng/mL cut-point on the basis of previous estimates.13
Initial estimates of the prostate cancer mortality rate given screen-detected cancer, and the corresponding rate given non-screen-detected cancer, were informed by examining the risk profile of patients in the ERSPC trial in light of published prognostic models for localised prostate cancer.14,15 Initial estimates were refined by calibrating the model against the results of the ERSPC trial. The 10-year prostate cancer mortality probability was consequently estimated to be 16% for men with non-screen-detected cancer, and the relative risk of prostate cancer mortality for men with screen-detected prostate cancer was 0.87. Age-specific non-prostate cancer mortality rates were calculated from Australian population statistics.
Each health state was assigned an estimate of the resources required to provide appropriate health care. These costs were estimated from the perspective of the Australian health care system and included the direct health care costs associated with the natural history of prostate cancer. Box 3 summarises costs included in the model, along with the ranges that were applied in the sensitivity analyses.
The net effectiveness of each strategy (PSA screening versus no PSA screening) was quantified in terms of quality-adjusted life-years (QALYs). The average QALYs were calculated by weighting the time spent in each health state by the health-related QOL value (utility) associated with that state, where 0 = death and 1 = full health. We assumed that the effect of prostate cancer (and its treatment) on QOL was equivalent to a decrement of 0.05 in utility averaged over the entire survival period, with a plausible range of 0.00 to 0.10. This range for the decrement in utility was chosen on the basis of evidence from longitudinal evaluations of QOL in prostate cancer.16 We further assumed that QOL during the 12 months before death from prostate cancer was associated with an additional 0.50 reduction in health state utility.17
A half-cycle correction was applied in the Markov process when calculating the expected outcomes of the screening and non-screening strategies, and a 5% discount rate was applied to both future costs and benefits.
The model described above was run on three simulated cohorts of 50-year-old men: a cohort with an average level of risk of prostate cancer (ie, risk was age-adjusted but otherwise comparable to that of men enrolled in the ERSPC trial); a second cohort with high-risk of prostate cancer; and a third cohort with a very high risk of prostate cancer. The base-case prostate cancer incidence rates were increased by a factor of 2 for the high-risk simulated cohort and by a factor of 5 for the very high-risk simulated cohort.
Results
For men with an average risk, PSA screening led to an additional 2.7 quality-adjusted life-days (14.3 undiscounted) at an additional cost of $2185, giving an incremental cost-effectiveness ratio (ICER) of $291 817 per QALY gained. For the high-risk cohort, PSA screening led to an additional 8.3 quality-adjusted life-days (43.0 undiscounted) at an additional cost of $2519, giving an ICER of $110 726 per QALY gained. For the very high-risk cohort, PSA screening led to an additional 32.9 quality-adjusted life-days (161.2 undiscounted) at an additional cost of $2755, giving an ICER of $30 572 per QALY gained (see Box 4 for detail on the cumulative event rates).
PSA screening was associated with a net gain in QALYs under many, but not all, of the plausible scenarios run in the sensitivity analyses (Box 5). A threshold for effectiveness, beyond which screening was detrimental (ie, leading to a reduction in QALYs), was found in the following scenarios:
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when the utility of prostate cancer (diagnosis and treatment) was set to less than 0.93 for the average-risk cohort, and less than 0.91 for the high-risk cohort;
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for all risk cohorts when the annual reference rate of non-screen-detected prostate cancer given no screening was less than approximately 0.5%;
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for average- and high-risk cohorts when the annual reference rate of asymptomatic (screen-detectable) prostate cancer was greater than approximately 0.7%; and
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for the average-risk cohort when the annual rate of annual rate of death from prostate cancer given non-screen-detected prostate cancer was less than 1.14%.
Sensitivity analyses on financial costs showed PSA screening to always be more costly than no screening. The most influential parameters on the incremental cost of screening included the cost of the PSA testing, the cost of treatment for prostate cancer, the annual rate of non-screen-detected prostate cancer given no screening, the annual rate of screen-detectable prostate cancer and the relative risk of non-screen-detected prostate cancer given screening.
Discussion
PSA screening was associated with a net gain in QALYs for all patient risk groups under many, but not all, of the plausible scenarios explored in our model. The harms of screening outweighed the benefits when the incidence of non-screen-detected (poorer prognosis) cancers was varied towards the lower end of the range tested. For average-to-high-risk groups, PSA screening was also estimated to be harmful when the incidence of screen-detected (better prognosis) cancers was estimated at the higher end of the range tested, and when the QOL impacts of prostate cancer treatment exceeded a relatively modest threshold.
PSA screening was not found to be cost-effective for men with an average risk of prostate cancer. We estimated that for a 50-year-old man with average risk, PSA screening would lead to an average additional $2185 per individual screened, with negligible increase in quality-adjusted survival. The cost-effectiveness of screening remained unfavourable for the high-risk cohort at $110 726 per QALY gained, but was considerably more attractive for the very high-risk group at $30 572 per QALY gained. While there is currently no explicit threshold for an ICER at which an intervention is considered cost-effective for funding purposes in Australia, recent MSAC assessments have not recommended public reimbursement for preventative interventions with ICERs well over this amount.
The prostate cancer treatment costs we projected from past data may be an underestimate of future costs, assuming that access to a growing number of newer and more costly pharmaceutical therapies increases over time. The upper limit of the treatment cost estimate used in our sensitivity analysis was chosen to explore the consequence of this uncertainty, and we found that conclusions were unchanged.
Our findings have direct implications for the strategy of providing personalised risk information to the subset of men who are actively seeking PSA screening.2 Assessing patient family history to identify men at 2- to 3.5-fold increased risk of prostate cancer can be used to identify a group of men for whom PSA screening will provide a greater net clinical benefit;22 however, our findings suggest that these benefits are not large enough to produce a favourable cost-effectiveness ratio.
The use of molecular markers to identify patients at very high risk for more targeted screening is promising. However, critical factors include the prevalence of very high risk markers, the cost of risk assessment and the potential for cost offsets if men identified at average risk are less likely to favour screening. Only a relatively small proportion of the population of 50-year-old men is likely to be identifiable at very high risk (ie, ≥ five times the average risk), based on recent studies. The prevalence of high-risk mutations in the BRCA1 and BRCA2 genes, for example, has been estimated to be only around 0.5% in the general population.23 According to a five-single-nucleotide polymorphisms (SNPs) prostate cancer risk factor model,11 only 0.3% of men in the control group fell into the very high-risk category (ie, ≥ five times the average risk), while in a 25-SNP model, not even those at the upper 99th percentile of SNP profile distribution reached this level.12
The costs of testing across the general population to identify a relatively small group of very high-risk men (comprising less than 1% of the general population) will be critical determinants of cost-effectiveness. The current costs of genetic tests such as that for BRCA1 and BRCA2 are relatively high, and thus population-based testing could not be justified to guide PSA screening.
The cost of providing a risk assessment has the potential to be offset by cost savings if those found to be at moderate levels of risk subsequently choose not to pursue routine PSA screening. The degree of cost offset would be a function of, among other things, the accuracy of the risk assessment tool, the distribution of risk profiles across the target population and the ability of information from a personalised risk assessment to influence patient preferences for PSA screening. Further empirical research is needed on the potential of these factors to offset the cost of personalised risk assessment.
Our analysis uses the most recent evidence from randomised trials of PSA screening to provide a better understanding of the potential impacts on survival, QOL and costs of PSA screening as a function of personal risk. The results of our study are limited by the rigour of the available evidence from randomised trials and do not obviate the need for longer-term randomised trials in higher risk men,24 or for data from ongoing observational studies such as IMPACT (Identification of Men with a Genetic Predisposition to Prostate Cancer: Targeted Screening in BRCA1/2 Mutation Carriers and Controls), which is evaluating annual PSA screening in men with a BRCA1 or BRCA2 mutation.5 Although our model suggests that there is potential for PSA screening in very high-risk cohorts, it may underestimate the harms associated with screening if the effect of false-positive PSA test results and biopsies on QOL is not short-lived. Further data are required on the impact of false-positive results and associated biopsies on QOL. Our model does, however, formally synthesise the current available evidence on PSA screening in response to the important clinical question of its potential value in higher risk populations, while incorporating the QOL impact of diagnosis and treatment as well as financial costs in the Australian context.
A major issue applicable to all evaluations of PSA screening is the lack of a reliable test for determining the subset of screen-detected prostate cancers that warrant radical treatment. A test that could reliably distinguish prostate cancers that are both amenable to radical local treatment and likely to be morbid and life-threatening without local treatment would have a favourable impact on the effectiveness and cost-effectiveness of screening.
In conclusion, PSA screening was not found to be cost-effective for men at an average-to-high risk of prostate cancer, but may be cost-effective for men at very high risk. Inexpensive approaches for identifying men at very high risk are needed, as is further research on the size of clinical benefit of early detection in this population and the potential for costs of risk-assessment to be offset by reduced costs of PSA screening.
1 Schema of Markov process modelling the policy of prostate-specific antigen (PSA) screening every 4 years versus the policy of no PSA screening in a simulated cohort of 50-year-old men*
* All men in the simulated cohort entered the Markov process with no prostate cancer (the upper-left green rectangle in diagram). Given a policy of no PSA screening, and at the completion of each 1-year cycle, men in the simulated cohort could transition to any of the states represented by the green rectangles, following the direction indicated by the arrows. Given a policy of PSA screening, men in the simulated cohort could transition in accordance with any arrows (blue or black) to any health state. Under either policy, the model allowed men in the simulated cohort to remain in any of the transient states (states other than death) for more than one cycle. The likelihood of transitioning to another state at the completion of each 1-year cycle was governed by the probabilities in Box 2.
2 Decision model: probabilities and utilities used to estimate lifetime net benefit and cost of prostate-specific antigen (PSA) screening versus no screening in simulated cohort of 50-year-old men
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Low and high range corresponds to estimated test characteristics at |
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Screen-detected prostate cancer incidence rate in screening arm |
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Incidence of non-screen-detected prostate cancer given no screening |
Prostate cancer incidence rate in screening arm of ERSPC,9 |
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Relative risk of non-screen-detected prostate cancer given screening |
Ratio of incidence rates for non-screen-detected cancers, given screening, versus control arms of ERSPC.9 Low–high, 80%–120% |
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Incidence of prostate cancer death given non-screen-detected prostate cancer |
Initial estimates based on Gleason score profile of patients in the |
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Relative risk of death from prostate cancer given screen-detected prostate cancer |
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ABS mortality data (adjusted to exclude prostate cancer deaths) |
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Effect of prostate cancer (and its treatment) on quality of life |
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Utility of health state 12 months before death from prostate cancer |
Quality of life during the 12 months before death from prostate cancer |
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ABS = Australian Bureau of Statistics. ERSPC = European Randomized Study of Screening for Prostate Cancer.9 |
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3 Unit costs for health care resources included in Markov model
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18*† |
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18*¶ |
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19* |
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AIHW = Australian Institute of Health and Welfare. MBS = Medicare Benefits Schedule. PSA = prostate-specific antigen. |
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4 Projected clinical outcomes of prostate-specific antigen (PSA) screening versus no screening in a simulated cohort of 50-year-old men*
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Cumulative incidence per 1000, lifelong total (10-year projected outcomes) |
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na = not applicable. * Estimates based on 1 000 000 microsimulations. |
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5 Results of sensitivity analyses showing difference in quality-adjusted life-years after each of the parameters shown in Box 2 was varied through its plausible range*
PC = prostate cancer. PSA = prostate-specific antigen. * Each parameter in Box 2 was varied through its plausible range in a series of one-way sensitivity analyses for each of the three simulated cohorts. The results are presented in the form of a tornado diagram with horizontal bars showing how the net effectiveness of PSA screening changes as each parameter was varied through its plausible range. Values to the right of the vertical line represent a result indicating a net benefit and those to the left represent a result indicating a net harm.