The Ethics of Prostate Cancer Screening
Michael Funaro
Advisor: H. Gilbert Welch, MD, MPH
Culminating Project for Ethics Minor
Dartmouth College
Hanover NH 03755
Dedication
I dedicate this work to my parents, my brother and J. M.
2
Acknowledgements:
I am indebted to my advisor, H. Gilbert Welch in this work. He piqued my interest in this
material more than two years ago in his class and has continued to foster this interest. I thank
him for his time, his insight and his patience.
I would also like to thank the many that helped in distributing the survey, and those who
offered feedback along the way. Michael Evans, Peter Kulbacki, Adrienne Stone, Frank
Roberts, and the staff of their respective departments.
I would also like to thank Professor Donovan for allowing me to pursue this project.
3
Overview:
Prostate cancer is the second most common cancer in American men. It is also the
second leading cause of cancer deaths for men. Prostate cancer is commonly detected through
screening techniques like the PSA exam. The treatment of prostate cancer is complex and
involves invasive surgery that can often include long-term impotence and incontinence.
Prostate cancer, its apparent incidence and the number of patients treated have all been
affected by prostate cancer screening. Recently, several government agencies and associated
panels have rescinded their recommendations for prostate cancer screening in the general
population. While much work has been done on the epidemiology of prostate cancer, very
little attention has been paid to the preferences of patients, and even less to the ethical
concerns of such treatments. This work is divided as follows:
i.
Background of Prostate Cancer
ii.
Screening and Treatment
iii.
False Positives with Prostate Cancer Screening
iv.
Overdiagnosis
v.
Original Survey
vi.
Forces at Play: Money, Laws and Feelings
vii.
Discussion
i. Background of Prostate Cancer
4
Prostate cancer is the second most common cancer in American men after skin cancer.
There were an estimated 186,000 new cases in 2008, accounting for 25 percent of all new
cancer cases in males.1 It is also the second leading cause of cancer deaths for men in the US,
with 28,660 deaths attributed to prostate cancer in 2008.2 Given that it is such a common
cancer, it has received considerable attention from the medical community. It is frequently
detected early and has high 5-year survival rates. Of the diagnoses made in 2009, an estimated
91% of them were for cancer in preliminary stages. When found in preliminary stages, the 5year relative survival rate approaches 100%.3 Many of those involved in the treatment of
prostate cancer frequently point to the fact that before any sort of metastasis (spreading of
cancer cells to other areas of the body) occurs, the entire prostate can be removed or in some
cases, cancer can be treated locally.
The prostate is a small endocrine gland that is present in males but not females. It is
nestled below the bladder, surrounds the urethra, and abuts the rectum. This entire area is
further enclosed with numerous muscles and nerves, making it a complicated area to image
and treat. The prostate is mainly involved in reproductive functions, excreting several
substances that are chemically supportive of sperm and promote fertilization.4 While these
functions are important in the reproductive years of an individual, they largely become
irrelevant to individuals who are no longer attempting to father children. Prostate cancer tends
to occur later in life.
1
Jemal A. Et Al. CA Cancer J Clin 2008;58:71–96
Jemal A. Et Al. CA Cancer J Clin 2008;58:71–96
3
Thun, MJ. Et Al. Ca Cancer J Clin 2009;59:225-249
4
Anatomy of the prostate gland. Ohio State Medical Center.
http://medicalcenter.osu.edu/patientcare/healthcare_services/prostate_health/anatomy_prostate_gland/Pages/inde
x.aspx
2
5
Cancer is the uncontrolled growth of non-somatic cells within the body. In the context
of prostate cancer, cancer cells emerge in small areas within the prostate. In the event that
they continue to grow, the small areas of cells expand, and grow first within the confines of
the prostate. There are different types of prostate cancer cells. Some may grow aggressively
and rapidly, while others may grow very slowly.5 The majority of prostate cancer is the
slower growing variety. In some cases, the cells may undergo metastasis and spread outside of
the prostate gland. Once outside of the prostate gland they may spread to the surrounding
tissues and bones.
Though somewhat uncommon, prostate cancer can manifest with symptoms. This is
especially true of later stages, as the earlier stages typically do not show any symptoms.
Symptoms with the later stages can include nocturia (the need to urinate in the middle of the
night), painful urination, blood in the urine, and difficulty in starting and stopping urination.6
Numerous problems can arise with the prostate later in life. In addition to prostate
cancer, many men suffer from benign prostatic hyperplasia (BPH), an enlargement of the
prostate that can lead to problems with urination and other urinary tract symptoms.7 Prostatitis
is another common issue that leads to ongoing pain in the pelvis due to inflammation and
sometimes swelling of the prostate.8 These conditions, among many others, share the same
general symptoms with prostate cancer, particularly urinary issues and mild pain. A patient
presenting these symptoms, if he were of an appropriate age, would likely be tested for
prostate cancer, among the other diseases.
5
Ribiero da Silva, MN. Actas Urol Esp. 2012 Apr 18
Prostate Cancer. The Mayo Clinic Patient information center. http://www.mayoclinic.com/health/prostatecancer/ds00043/dsection=symptoms
7
A Thorpe, D Neal. Lancet 2003; 361: 1359–67
8
Collins MM, Stafford RS, O'Leary MP, Barry MJ (1998). "How common is prostatitis? A national survey of
physician visits". J. Urol. 159 (4): 1224–8
6
6
ii. Screening and Treatment
Prostate cancer screening is when doctors look for cancer in patients who display no
symptoms of cancer. Cancer screening has become commonplace in western society, and is
practiced for many cancers. Women are encouraged to have mammograms, both sexes are
encouraged to have colonoscopies performed once they reach 50, and until very recently, men
were recommended to have a Prostate Specific Antigen or PSA test performed. Unlike breast
cancer, prostate cancer does not manifest in an externally palpable lump. Instead, at best it can
be possibly detected through a digital rectal exam. However, these tests are extremely limited
and only allow a urologist to examine a small portion of the prostate.9. As a result, before the
advent of the PSA exam, there was certainly a desire on the part of physicians for an easier
test, like a blood test.
The PSA test was introduced in 1987 by Abbot Labs. It is a reliable test for BPH but a
relatively poor test for prostate cancer.10 The test works by detecting levels of a chemical
called prostate specific antigen in the blood. Prostate specific antigen is always present in the
blood, but higher levels are sometimes associated with conditions of the prostate like BPH
and prostate cancer. Doctors and the medical community have chosen various “action levels,”
or threshold levels of PSA in the blood—concentrations of the chemical that are though to be
indicative of the presence of prostate cancer or warranty further investigation through a
biopsy.
9
Koulikov D. ISRN Urol. 2012;2012:456821. Epub 2012 Feb 15.
Roehrborn C.G. BJU Int. Suppl. 1: p.21, 2004.
10
7
Typically, if a PSA test comes back with a “positive result,” or a value that based on
the established action levels suggests that there might be prostate cancer present, a biopsy is
performed. A biopsy entails inserting a small needle like device into the prostate (typically
through the rectum). Through this process, samples of tissue are extracted and subsequently
sent away for analysis by a pathologist. Generally, multiple samples are taken from different
regions of the prostate. More samples typically show more cancer. When a pathologist finds
cancer, many patients are encouraged to proceed with treatment of their newly diagnosed
cancer.
Treatment for prostate cancer comes in multiple forms. Prostate cancer is typically
treated through surgery and/or radiation.11 These procedures include brachytherapy, radical
prostatectomy, radical prostatectomy with nerve sparing, external-beam radiation therapy, and
conformational external beam radiation therapy.12 Radical prostatectomy involves the
removal of the prostate gland through surgery. There are multiple approaches to surgical
removal; however, all of them are fairly extensive and invasive. In radical retropubic
prostatectomy, an incision is made in the lower abdomen and the prostate is accessed from
behind the pubic bone.13 In radical perineal prostatectomy, prostate is excised through the
perineum. As this technique makes it very difficult for nerves to be spared, it has become less
common.14 While radical prostatectomy is an invasive procedure regardless of which way it is
performed, through the use of robotic surgery systems it is possible to limit the size of the
11
Nelson WG, et al. Prostate cancer. In: Abeloff MD, et al. Abeloff's Clinical Oncology. 4th ed. Philadelphia,
Pa.: Churchill Livingstone Elsevier; 2008:1653.
12
Wilt, TJ. 18 March 2008 Annals of Internal Medicine Volume 148 • Number 6 435
13
Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol
1982;128(3):492-497.
14
Frazer HA, Robertson JE. The Journal of Urology [1992, 147(3 Pt 2):888-90]
8
incisions made and the overall disturbance to the area.15 There is also some evidence to
suggest that these techniques of prostate cancer removal are associated with recurrence of
cancer.16
The side effects of prostatectomy are immediately relevant to any discussion of
prostate cancer treatment as they are both common and have significant ramifications for
quality of life of patients. Prostatectomy results in both short and long-term side effects. Short
term side effects and risks include incontinence, postoperative pain, swelling, and erectile
dysfunction.17 These effects are typically seen as being short term when they persist weeks to
a few months. Long-term effects are those that last for months to years after the procedure.
The most serious long-term effects that accompany prostatectomy are again incontinence and
impotence.18 While different medical centers post different outcomes, it is typically reported
that somewhere between one-third and one-half of those treated with prostatectomy have long
term incontinence or impotence.19 The inability to control one’s bladder or to have an erection
is understandably relevant to the quality of life of individuals undergoing radical
prostatectomy.
Radiation based therapies are another approach to prostate cancer treatment. These
techniques may be used when the cancer has spread, making surgical removal impractical or
ineffective.20 Radiation is administered through the use of an external apparatus or through
the use of radioactive seeds that are implanted in the prostate. Implanted treatments are
typically left in the body indefinitely and become less active over time. The seeds or external
15
Tewari A, UROLOGY 60 (4), 2002.
Barocas, DA. J Urol. 2010 Mar;183(3):990-6. Epub 2010 Jan 18.
17
Perl M, Waldmann A, Pritzkuleit R, Katalinic A. Urologe A. 2012 Jan 27
18
Geary, EC. Et Al. The Journal of Urology Vol. 154, 145-149, July 1996
19
Ibid.
20
NIH Xplain. Vol. 154, 145-149, July 1996
16
9
radiation are administered on the basis of a treatment plan, which has been developed through
the assistance of biopsy and other test results that give an idea of the size and scope of the
cancer.21
Radiation and radiotherapy carry similar side effects to surgical approaches. In some
cases it is advertised as having reduced incidence of complications versus prostatectomy.22
The incidence of incontinence and impotence with radiation are generally similar to that of
radical prostatectomy.23 Due to the spread of radiation and its toxicity to elements of the
digestive system, there are also issues of rectal damage following these treatments.24
While this work is not primarily focused in the symptoms of prostate cancer nor the
implications of treatment, it is essential to consider the ramifications of prostate cancer and
prostate cancer treatment for the individual. The prostate is in an anatomically complex area
of the human body, and that it is in close proximity to organs for reproduction and excretion
of solid and liquid wastes. Any treatment of prostate cancer will have, at the very least, effects
on these systems in the short term. All of these techniques and means of treatment are
accompanied by the potential for significant side effects that will become ongoing for months
or years, and in some cases the entire life of the patient. In some contexts these effects may
last for the remainder of the patient’s life. Moderate to severe incontinence can necessitate
significant life changes, and the effects of this in a 50-year old can be very pronounced.
Similarly, for sexually active couples, the sudden and ongoing cessation of sexual activity
may produce great hardship in the relationship. Both of these conditions have the potential to
21
Susil, R. C., Camphausen, K., Choyke, P., McVeigh, E. R., Gustafson, G. S., Ning, H., Miller, R. W., Atalar,
E., Coleman, C. N. and Ménard, C. (2004), System for prostate brachytherapy and biopsy in a standard 1.5 T
MRI scanner. Magn. Reson. Med., 52: 683–687. doi: 10.1002/mrm.20138
22
Wagner, W. Et Al. ANTICANCER RESEARCH 31: 3903-3908 (2011)
23
Lim, AJ., The Journal of Urology Volume 154, Issue 4, October 1995, Pages 1420–1425
24
Chen RC. BJU Int. 2012 Apr 13. EPub Ahead of Print.
10
provide significant stress and psychological effects for the patient. While many would choose
these outcomes over an untimely death due to prostate cancer, it is essential to ensure that
those who are being treated and subjected to these outcomes are indeed avoiding cancer
deaths.
iii. False Positives with Prostate Cancer Screening
The mainstay of prostate cancer screening, the PSA exam, has a checkered past. It has
long been attacked for poor specificity. The specificity of a test relates the tests ability to
correctly identify those without disease. A test with high specificity will reduce the number of
false positives, or individuals who are told that they have a disease that actually do not. There
was originally considered to be reasonable specificity at a threshold of 10 ng/mL for BPH or
prostate cancer, but low specificity below these PSA levels.25 This 10 ng/mL was then taken
to be an action level. The author of one of the early journal articles on the use of the PSA
exam for hyperplasia (BPH), Thomas Stamey M.D. of Stanford, notes that “the elevation in
PSA that accompanies the hyperplasia…precludes the use of PSA concentration as a means of
screening for prostate cancer.”26 Unfortunately, this marginal statement was not presented as a
salient point of the article, and instead the article was placed among the many others that
mentioned PSA screening for prostate cancer.
The poor specificity did not deter physicians from considering the results of PSA
exams for prostate cancer. At the same time, the level of action thresholds was being reduced,
25
Horan A. The Big Scare: The Business of Prostate Cancer. 2009. Page 30.
Stemey TA Preoperative serum prostate-specific antigen as a serum marker for adenocarcinoma of the prostate
N. Eng. J. Med. 317: 909, 1987.
26
11
whereby the level for action was reduced to a PSA blood level of 4 ng/mL.27 Many regarded
this level as being too low, as there was worse specificity at this level. Many without cancer
were being told that they had cancer. Simultaneously there were also many individuals with
PSA scores below 4 ng/mL who did have prostate cancer, leading some to suggest that the
threshold should have been even lower.28
The connection between PSA tests, BPH and prostate cancer was ultimately the
subject of dispute and confusion in the medical community. PSA tests that came back with
high values of PSA prompted doctors to order biopsies, and many of these biopsies came back
positive for cancer. However, the incidence of prostate cancer increases with age. In a study
of 60 year-old men who died of other causes, 60 percent had non-palpable prostate cancer on
autopsy.29 The initial action point of 10 ng/mL was subsequently lowered to 4 ng/mL, despite
a lack of significant evidence to support such a decision. In addition, scores of journal articles
shared many cases that were revealed flaws with the proposed action levels. They
overwhelmingly suggested that there were flaws with the test and that it was not a reliable
indicator of prostate cancer. An article in the New England Journal of Medicine reported that
an action level of 4.0 ng/mL of PSA had 54 percent specificity in older men who had BPH.
The same authors noted that 12 and 23 percent of men who have PSA scores between 2.5 and
4.0 ng/mL and no indication on digital rectal exam still have prostate cancer.30 To an outsider,
this data certainly does not suggest that the PSA exam is a trustworthy test. Some
considerations showed that using a PSA exam at the lower action thresholds was actually
27
Lilja, A. Nature Reviews Cancer 8, 268-278 (April 2008)
Ibid.
29
Punglia R.S. et al. NEJM 349: 355, 2003.
30
Barry, MJ. NEJM. N Engl J Med 2001; 344:1373-1377
28
12
comparable to flipping a coin in determining whether or not a patient had prostate cancer.31
Over time, modifications were made that brought specificity for prostate cancer of the PSA
exam over 50%, but nowhere near the common 80% specificity standard to which most other
diagnostic tests are held.32 Specificity values of this range very little value in a test’s results,
especially when men aged 60 to 70 have a 60% incidence of prostate cancer.33
iv. Overdiagnosis in Prostate Cancer Screening
Overdiagnosis is the diagnosis of disease in an individual when the individual was
never destined to develop the disease or experience symptoms from it.34 Applied to prostate
cancer, this then entails finding and diagnosing cancer in individuals who were never going to
experience symptoms of prostate cancer, and would have died from some other disease. The
statistics in the first section made prostate cancer appear an overwhelmingly common and also
dangerous cancer—it is the second most common cancer in men, with almost 200,000 new
cases found in American men on an annual basis. This certainly is a high incidence. But the
incidence is arguably as high as it is because doctors are actively looking for prostate cancer.
The 28,000 prostate cancer deaths per year mentioned earlier amount to approximately a 3%
chance of dying from a prostate cancer death.35 And as mentioned earlier, the incidence of
prostate cancer in those who do not display symptoms is alarmingly high, with 60 percent of
sixty year olds having prostate cancer on autopsy for non-cancer death. In healthy males in
31
Horan 31.
Horan 33.
33
Horinaga, M. J. Urol. 168: 986, 2002.
34
Overdiagnosed introduction page xiv.
35
Overdiagnosed page 47.
32
13
their twenties, 10 percent had prostate cancer.36 Given that 10 percent of twenty year olds do
not die from prostate cancer, and that 60 percent of 60 year olds have prostate cancer, the fact
that 3 percent of men die from prostate cancer begins to suggest that it really is not all that
dangerous of a cancer. But there is a lot of cancer out there waiting to be found. And for those
doctors who find it, there is cancer to treat.
The amount of prostate cancer found is highly dependent on both PSA exams and
biopsies. Given a vast pool of patients with cancer, it is just a matter of how low the threshold
is for PSA and how frequently and how thoroughly the prostate is biopsied. There is
considerable concern and debate for the level of PSA in the blood that is regarded as the
action level—that which is supposed to warrant a biopsy. When physicians or care
organizations lower the action level, more people are included in the portion of individuals
believed to have cancer, and more biopsies are then ordered. When more biopsies are ordered,
doctors are more likely to find more cancer.37 And when biopsies are more exhaustive, and
take more samples, there is also a greater likelihood of finding cancer within each prostate.
And so the biopsy with more than 20 needle biopsies mentioned earlier does not just make the
doctor more money, it increases the chance of finding cancer. And once cancer is found, most
people want it treated.
The logical question that follows this discussion is whether prostate cancer deaths are
being avoided. This is a somewhat difficult question to answer. Surely, with the PSA exam
and the societal penchant for cancer screening, the number of cases of cancer has risen
rapidly. However, the question or whether prostate cancer screening is averting prostate
36
37
Sakr WA. Et. Al. Eur Urol. 1996;30(2):138-44.
Overdiagnosed 50.
14
cancer deaths is actually a much more important question. If doctors are treating patients
invasively for a cancer, in a manner that renders them impotent and incontinent, one would
hope that cancer deaths are actually being prevented. Whether or not screening reduced
cancer mortality was the subject of two exhaustive trials, one in Europe and one in the United
States. In the American study, it was found that after 13 years of follow-up, there was no
decrease in mortality due to prostate cancer with regular screening versus opportunistic
screening.38 This study involved nearly 80,000 participants for 13 years. There was also
contamination of the study populations. The European study involved 182,000 men and found
a slightly different result. It was found that regular PSA screening was associated with an
absolute reduction of 0.71 deaths per 1000 men.39 Given the incidence of prostate cancer in
the study population, the authors calculated that 1410 men would have to undergo screening
and 48 men would have to be treated in order to prevent a single prostate cancer death.
Certainly, there is some benefit here. However, the potential harm would most likely
outweigh the benefit for most men.
These trends of prostate cancer screening and prostate cancer detection can be viewed
from another angle. If doctors were truly finding harmful cancers with PSA testing, and
subsequently treating them with prostatectomy, it would be reasonable to expect that cancer
mortality would decrease significantly. However, as the European study mentioned above
suggested, this is not the case. Consider the following figure:
38
39
Andriole GL, et al. J Natl Cancer Inst (2012) 104(2): 125-132.
Schroder, FH. Et al. N Engl J Med 2009; 360:1320-1328
15
250
200
Incidence per
100,000
men
150
New diagnoses
100
Prostate Cancer Deaths
50
0
1975
1980
1985
1990
1995
2000
2005
2010
Year
Figure 1. New Diagnoses and Deaths from Prostate Cancer, 1975-2009.40
Figure 1 illustrates the events following the advent of the PSA exam very clearly.
Following the introduction of the exam there was an enormous spike in the reported number
of diagnoses of prostate cancer. If there were truly more cancer, one would expect more
cancer deaths, perhaps a few years down the road. However this trend is not seen. There is a
slightly heightened incidence of prostate cancer death just a year after the spike of 1993, but
nowhere near in magnitude to that of the increase in diagnosis. This graph shows a rapid
increase in the number of prostate cancer diagnoses coincidental with the advent of the PSA
exam, while cancer deaths remained fairly stable.
Very recently, the recommendation for prostate cancer screening by the US
Preventative Services Task Force (USPSTF) was changed. The USPSTF is an organization
that makes suggestions on the preventative medical procedures like cancer screening. In
October 2011, this group concluded that “Prostate-specific antigen–based screening results in
40
Data from SEER database.
16
small or no reduction in prostate cancer–specific mortality and is associated with harms
related to subsequent evaluation and treatments, some of which may be unnecessary.”41 While
many in public health and perhaps even some urologists laud such a recommendation, as the
data above would also support, it is also clear that this recommendation is not being followed
universally. For example, billionaire philanthropist Warren Buffet recently had a high PSA
score, which prompted him to pursue treatment for prostate cancer, despite being 84 years
old.42 This is not only in disagreement with the latest recommendation for individuals in the
general population, but actually against a more explicit recommendation for men from the
same task force for those over the age of 75. The task force states “The USPSTF recommends
against screening for prostate cancer in men age 75 years or older.”43 This actually has some
implications over the underlying regard for PSA testing of the doctor who administered the
test and Warren Buffet. Presumably Warren Buffet sees a high profile doctor, and wishes to
live a long life. In administering the PSA, there is an underlying assumption that finding
prostate cancer and treating it will lead to a longer life expectancy. This is hardly supported in
the literature, especially for someone Buffet’s age.
41
http://www.uspreventiveservicestaskforce.org/uspstf12/prostate/prostateart.htm
http://www.npr.org/blogs/health/2012/04/18/150892066/what-we-can-learn-from-warren-buffets-prostatecancer
43
http://www.uspreventiveservicestaskforce.org/uspstf/uspsprca.htm
42
17
v. Original Survey and Survey Results
A thorough exploration of the preferences associated with screening and treatment
entailed the design of an original survey. The survey includes information about basic
demographics (age and gender) and then proceeds to ask individuals about a sequence of
hypothetical conditions concerning prostate cancer. These are included and described below.
The survey was distributed to Dartmouth College Facilities and Operations employees, police
departments, fire departments and public works departments. Approximately 450 surveys
were distributed and participation was voluntary. The survey received approval from the
committee for the protection of human subjects of Dartmouth College and the Geisel School
of Medicine at Dartmouth College. The questions are included individually below, along with
the rationale and results for each question. The full survey is included (addendum 1). Care
was taken to keep the survey to a single double-sided page, to encourage completion. A total
of 30 completed surveys obtained. All completed surveys were from males. The mean age of
the individuals completing the survey was 50 years of age. The first and third quartiles for age
were 44.25 and 55.75, respectively.
Question 1. Screening in the absence of harms.
18
This question sought to see how many deaths needed to be averted for individuals to bother
with a screening process. Screening was not explicitly defined, but it can be reasonably
inferred that screening would entail some sort of test at a medical facility. In response to this
question, 98% of individuals chose screening for 100 prostate cancer deaths averted, 73% for
10 averted, 63% for one death averted, and 40% for 0.1 deaths averted per 1000 screened.
This is largely in keeping with what is expected. An overwhelming number of individuals
would choose prostate cancer screening in the absence of any harms. There does come a
point, however, where the number of cancer deaths avoided becomes too small. This too is
easily rationalized—in the event that an individual is highly unlikely to benefit from
screening, at some point, even without harm, the bother of another procedure and another
doctor’s visit is unjustified.
Question 2. Screening in the presence of harms
The question was first prefaced with the following:
This text was included to present a more realistic consideration for prostate cancer screening.
As discussed earlier, prostate cancer is associated with overdiagnosis. The side effects of
treatment and the incidence of these side effects are also included. This provokes survey
19
participants to consider some of the drawbacks of prostate cancer screening and reinterpret the
same set of conditions.
The survey immediately presented the following:
The results were that a slightly lower number of participants chose each level of benefit. 87%
of survey takers would still participate in screening where 100 avoided a cancer death, 63%
where 10 avoided a cancer death, 50% where 1 avoided a prostate cancer death and 27%
where 0.1 individuals avoided a prostate cancer death. This is consistent with what one might
expect. The awareness of the potential for side effects with treatment deters individuals from
participating in screening. The results of question 1 and 2 are illustrated graphically below
(figure 2).
20
Figure 2. Survey Results: Percent of Individuals choosing screening both where there are
harms and where there are no harms associated with screening.
The survey questions and accompanying text have not yet divulged how many might be
treated needlessly in order to achieve these outcomes; question two is somewhat ambiguous in
this regard, but is so out of necessity. It is not explicitly stated that men will receive treatment
who do not have cancer, but it is also highly unlikely that survey participants assumed that all
individuals screened would suffer these consequences.
Question 3. Outcomes with Rates of Overdiagnosis and Overtreatment
This survey item was first prefaced with the following text:
21
This statistic was a rounded version of the outcomes of the European study presented earlier.
The question then proceeded to access how many individuals could be needlessly treated for
the outcome of a single avoided cancer death to be worthwhile.
This question is notably different from the other two. Rather than considering benefit given a
specific harm, the participants are presented with a benefit and asked to choose a harm that
would be acceptable. The results of this question are most interesting to the discussion of
prostate cancer screening. As the previous section discussed, there is considerable
overdiagnosis with prostate cancer. In the event that overdiagnosis and needless treatment is
inexorable, it is important to consider at what level it is still acceptable to an individual
patient. In the event that the current situation is worse than their maximum accepted level,
then there is reason to suggest that screening is not suitable for those individuals, in so far as it
is not in keeping with their values.
Where two individuals were treated for a cancer that was never going to bother them,
90% of survey respondents elected screening. For five treated, 67% still elected screening.
22
Where 10 were treated, 53% still chose screening. The shift came between 10 and 25 treated
for cancer that was never going to bother them. For 25 treated, 37% elected screening (63%
abstained). These results were carried through exactly for the 50 treated needlessly scenario.
There was a slight reduction to 33% electing screening with the 100 treated needlessly
scenario. These results are illustrated in figure 3 (below).
Figure 3. Percent choosing screening versus the number of individuals overtreated to
avoid one cancer death.
The best estimate of those needlessly treated, as discussed earlier, is 50 per 1000
screened.44 These results show that the majority of survey participants would not elect
prostate cancer screening in this situation. If all of these conditions were effectively conveyed
to them at the time that they were offered a PSA exam, it is probable that they would not elect
to receive the exam, as they just have indicated in the survey. It should also be noted that
there are still reasonably strong percentages of those that would choose screening regardless
of the number of individuals overtreated. It is unclear whether these individuals find
44
European Prostate Cancer Study
23
avoidable cancer deaths completely abhorrent or still consider a life prevented to be worth the
incontinence, impotence and associated quality of life issues of whatever number of men.
Questions 4 and 5: Personal History of Treatment
Items 4 and 5 addressed the personal health history of the survey participant with respect to
prostate cancer and prostate cancer treatment. While these are not of crucial importance, it
was worthwhile to evaluate both of these questions. 47% of individuals had been screened,
while 47% of individuals had not been screened and 6% of individuals were unsure if they
had been screened or not. No individuals had been treated for prostate cancer.
Question 6. General health care preferences
24
This question sought to evaluate the general attitude of survey participants toward two
conditions in the consideration of individual health care and the invasiveness of tests and
procedures in pursuit of a longer life. This question intentionally pushed individuals to one or
other extreme—a few survey participants even wrote on the paper that their preferences were
somewhere between the two. Participants were all but evenly split between the two
scenarios—46% elected medical care to do everything to extend life despite inherent risks
possible while 54% preferred to avoid unnecessary interventions. These general preferences
manifested in the responses to question 3, concerning the acceptable level of overtreatment
that would be associated with prostate cancer treatment. In figure 4 (next page), it can be seen
that those who were willing to accept the risk of unnecessary treatment and intervention have
a greater tendency to choose screening where more overtreatment occurs versus those who
preferred to live without the inconvenience and harm of unnecessary medical treatment. This
confirms what is expected in that those who have fewer and less intense desires for aggressive
care also have a lower tolerance for an acceptable number of overtreated patients. This logical
result also begins to support the argument that the survey questions were well understood.
25
Figure 4: Percent of patients choosing screening for various numbers of individuals
overtreated, sorted by preference toward treatment style.
vi. Forces at Play
It would be naïve to turn a blind eye to the financial considerations of prostate cancer
screening and treatment. Both private medical practices and academic health settings require a
steady flow of business to stay afloat. Therefore private practice doctors like prostate cancer
patients, and so do academic institutions. There is tremendous revenue potential associated
with such screening. Even with Medicare reimbursement levels, a practice of three urologists
who perform 150 PSA exams per month can generate $19,565 in annual profit, simply from
giving the tests.45 Any false positive creates the opportunity for a biopsy. Medicare
45
Bankhead C. Urology Times. 32: p 22, Dec 2004.
26
reimburses doctors $97.03 per biopsy core.46 Many doctors perform as many as 21 cores,
which amounts to a $2073 bill for the government, and ultimately, the taxpayer. If
histochemistry is performed on each core another $1800 can be added to the bill.47 The point
here is that there is enormous money in positive results from a PSA test, whether or not there
is cancer. These profits actually trump the profits from prostatectomy.
Yet another driving force for the aggressive use of PSA exams and biopsy is fear of
legal ramifications from missing a case of prostate cancer. Many doctors are forced to
perform more biopsies than they feel is medically required for fear of lawsuits claiming
delayed detection of cancer by lack of a biopsy. This behavior is seen everwhere, including
salaried urologists in prepared HMO settings like Kaiser-Permanente, where there is arguably
little to no financial incentive for doctors to perform medical care that is otherwise
unnecessary.48 In one case, a PSA score of a patient was 4.1 ng/mL and it was not followed up
on. Two years later it was 4.8. Then it decreased again to 4.5 ng/mL. Five years after the
initial rise to 4.8 ng/mL, the PSA was 10.2 and advanced cancer was present. The patient then
underwent radical prostatectomy and sustained “injury”, and a $400,000 settlement was
obtained.49
A resident physician and his residency program were sued because they followed the
recommendation of the American Urological Association that the doctor discuss the benefits
and harms of PSA testing with a patient prior to drawing blood. The patient was later
subjected to a PSA without consent by another physician, and had a high PSA value,
indicating advanced cancer. Accordingly, he filed the aforementioned lawsuit and a jury made
46
Horan 35.
Ibid.
48
Horan 35
49
www.vaaglaw.com/cases
47
27
a judgment against the residency program for a million dollars.50 In a legal climate that
punishes those who do not relentlessly search for cancer, even when it is against the will of
the patient, the seemingly irrational use of the PSA exam begins to make sense.
The financial interests associated with prostatectomy are also worthy of brief
consideration. The surgical fees paid to a surgeon by Medicare for a radical prostatectomy are
in excess of $1300.51 These fees have declined over time and the reimbursement was
previously much higher. In addition, these relatively low rates are actually driving some
practitioners toward the use of radiation seeds, or a combination of radical prostatectomy and
seeds where it can be reasonably justified.52 It is now believed that 28% of urologists have
financial interest in an ambulatory surgical center.53 Androgen removal therapy makes
significant money for pharmaceutical companies who frequently kick it back to the
physicians, in one way or another.
The fact of the matter is that urology has molded around prostate cancer and
embraced its treatment as a significant source of its revenue. Together, screening and the
actual treatment bring considerable work to urologists. One urologist notes, on the expectation
of referring physicians, “If somebody is referred to a urologist by a non-specialist because of
an elevated prostatic specific antigen laboratory report, the die is cast.”54 Indeed, when
physicians are in a position to provide services and make money, they will likely do so.
Without getting overly entrenched in a discussion of reimbursement models, it is readily
apparent that prostate cancer treatment has become a significant source of revenue for
urologists. It is doubtful that, amidst rising administrative costs and decreasing
50
Merensten D. Jama 291: 15-16, 2004.
The Big Scare The Business of Prostate Cancer 166.
52
Ibid
53
McNett C.L. Health Policy Brief 14. (1): p3
54
The Big scare 168.
51
28
reimbursements from insurers, physicians will go out of their way to reduce the patient
volumes associated with certain procedures. This attitude is well illustrated by Anthony
Horan, MD, a urologist in private practice. He notes
As a solo private practitioner and therefore a small businessman once
again, I do not see any of my suppliers, my insurers, my power generators,
or my landlords lowering their prices because they are making too much
money. I do not see medical or hospital business expenses going down. I
do not see my son’s private college lowering their tuition. I see
administrators everywhere in Gucci shoes.55
It is unlikely that many physicians will readily question the efficacy of such procedures,
given this has the potential to raise financial hardship and threaten their business, their
practices, and their livelihoods.
While some of the evidence suggests that many men would be better off never
participating in any sort of prostate cancer screening, many others will still participate. It may
be voluntarily, or a PSA test may just be something that a family doctor has an ingrained habit
of ordering along with many other test items. However, there is another aspect that has been
overlooked. It is one thing to talk about prostate cancer from afar, and another thing to be
diagnosed with it.
I sat down with a professor who had undergone radical prostatectomy following a
diagnosis of prostate cancer. The professor reported that his encounter with prostate cancer
started with the nonchalant statement of a doctor who said, “I’m going to put a PSA into the
bloods” when performing a routine blood test for cholesterol levels. His PSA exceeded the
threshold. Then he was subjected to a biopsy. The biopsy results came by phone at 6pm, just
55
Ibid
29
as he was sitting down to dinner. The biopsy was positive for prostate cancer, and he was
assured that “what they saw was a stable situation.” He proceeded to tell about his experience
in traveling to a specialist on the opposite end of the country for cutting edge treatment with
what was then a novel robotic surgery apparatus (the daVinci system). He had paid out of
pocket for the procedure.
He encountered many of the side effects discussed earlier—namely incontinence and
impotence. The incontinence proved to be short lived. He reported that over time and with
focus, he felt his sexual performance had returned to 90% of where it once was. For sure, this
man had been one of the lucky ones. He had avoided cancer, but perhaps more importantly, he
had managed to maintain his quality of life. It is unclear whether his outcome is a product of
his surgeon and his surgical technique, or just luck, or likely some combination of the two.
Beyond his experience, what was interesting was his regard for the entire ordeal, and
for prostate cancer in general. Keep in mind that he is well over the hurdle, with favorable
results. Speaking of the entire ordeal he said, “It was a very positive experience, not a
nuisance.” He added “I had to make tough decisions and I feel good about it. It was positive
in that I had never had a surgical procedure in my life before, and positive that I was one of
the first people for the daVinci system.” He added that the inconvenience is always
“modulated against what you’ve avoided.” He feels as though he dodged a bullet.
And it is unfair to say with certainty that he did not dodge a bullet. His outlook on
prostate cancer was positive through and through. He maintained that “prostate cancer is one
of the good ones” but noted that “both the containability and dreadfulness are unique.” He
suggested that people should make a decision about whether or not they wish to pursue cancer
treatment after they have been screened and after cancer had been found, rather than before.
30
He felt that people should not run from cancer, and that if he had cancer, he wanted to know
about it. He remarked “I didn’t want to not know—cancer is cancer!”
Cancer is indisputably a terrible disease. The threat of metastasis and the thought of a
long and drawn out death that could have easily been prevented is certainly difficult to
contemplate. And while 50 people may have been treated needlessly to prevent a single
cancer death, the odd man out who has cancer is certainly not going to feel great about his
decision not to get screened or treated. However, at times it seems like the extent to which
prostate cancer suits the procedure becomes a selling point for prostatectomy. Though the
surgery has serious side effects, prostate cancer is frequently advertised as being “contained”
and patients are encouraged to seize a window of opportunity to capture the cancer before it
spreads.
While treatability is a good thing, it is essential that that treatability does not become
the cause for treatment. Doctors should not treat cancers in a scheme that offers no reduction
in mortality just because the cancers are treatable. The goal of medical care for cancer should
be ultimately to reduce mortality, not to get rid of cancers that would otherwise not cause
harm just because a doctor can eradicate them. Surely, for a patient diagnosed with cancer,
assurance of treatability is a compelling attribute and would lead one to elect treatment over a
cancer that is very hard to treat. But in the absence of any benefit and in the presence of harm,
this may be seen as a silly reason for a patient to make a decision.
31
vii. Discussion
The ethics of prostate cancer screening are complex. In general, the purpose of
medicine is understood to mean service to people who are ill, protection of the health of
individuals who are well, and the defense and reinforcement of other healthcare values that
may be undervalued or overlooked.56 When screening is administered, the patient generally is
not ill and has not expressly initiated a request for a test. As shown, a PSA test has the ability
to confer some benefit, but also has the ability to generate harm. A false positive causes
unnecessary anxiety and a cascade of unnecessary treatment, resulting in serious side effects.
A false negative might give false reassurance.
In medicine, there has been an ongoing conflict between patient autonomy and patient
management. With the increased emphasis on patient autonomy, patients are encouraged in
many healthcare settings to make their own informed decisions about healthcare. This
emphasis essentially shifts the decision making model from that based on paternalism—ie the
doctor knows best—to one in which the patient has ultimate authority.57 In an ideal autonomy
model, the provider provides adequate, unbiased information to the patient and the patient
then makes a decision about what his best for him and his lifestyle. In the context of prostate
cancer screening, however, patient autonomy can be fragile. A provider can very easily
“suggest” to a patient that he be screened for cancer. And unless the patient was well versed
on the PSA exam and prostate cancer screening before going to their doctor’s office, the
suggestion of a PSA test probably sounds like a good one. The doctor does not expressly
violate the patient’s autonomy, because in that moment the patient could have stopped him
and said that he did not want a PSA test, but this outcome seems highly unlikely. Whether this
56
57
Emanuel LL. Camb Q Healthc Ethics 2009; 9-151-68.
Ustun C., Ceber E. Preventative Medicine 39 (2004) 223-229.
32
constitutes a violation of autonomy is unclear, but it does certainly does lead to a perversion
of the patient’s ability to opt in or out of prostate cancer screening.
The reasons for a doctor ordering a PSA exam may be one or several of many. It could
be that he has yet to review the literature, or perhaps that he considers treating 50 individuals
to avoid a prostate cancer death worthwhile. It could be that he is simply stuck in time, and
practices medicine and orders the same tests that he did years ago. He may fear a lawsuit and
be hopeful that in finding prostate cancer early, rather than risking overlooking it, he can
avoid legal ramifications down the road from a flawed legal system, as many others have
faced. Maybe he has the ability to analyze the PSA exam and its results in his office, or
maybe he has a share in a surgical suite in which he would perform the eventual
prostatectomy if cancer is found. Maybe the doctor ordering the PSA is just a general
practitioner who golfs as a guest of his favorite urologist at the country club every Saturday.
Regardless of the doctor’s reasons for suggesting the test, they should be well grounded in
science and study, rather than in habit, coercive pressures and financial interests. It is
obviously important for a patient to ask why a certain screening test is being suggested; it is
also important for the provider to ask why he or she is suggesting the test. It is even more
important for the broader medical community to question their practices and their
recommendations in dealing prostate cancer.
The idea of patient autonomy in screening campaigns becomes flawed and eroded
with ongoing advertisements and public service announcements. While these have subsided
for prostate cancer, they are still very abundant for other cancers. When hospitals and patient
advocacy groups are constantly reminding individuals to go get screened for a cancer, with
simple but meaningful statements like “screening saves lives”, patients may even seek
33
screening, or at least, will accept offers for screening more readily from their doctors. It is
unreasonable to expect each and every patient to perform extensive research, learn about the
number of false positives, and the number of patients who may be needlessly treated in
pursuit of avoiding cancer deaths.
The delivery of reliable information to the patient becomes an inexorable task for a
physician who is administering a screening test to a patient if they intend to do so in an ethical
manner. Surely, many patients will take their doctors’ recommendations for prostate cancer
screening on faith. However, many others might react differently to tangible information and
hypothetical conditions. If patients being offered prostate cancer screening were issued a
simple statement that clearly informed them of the benefits and risks of cancer screening, they
would likely make more informed decisions. Depending on the data presented, it is likely that
many fewer would partake in cancer screening, as evinced by the survey. A sample of such a
statement would be as follows.
Prostate cancer screening is when doctors look for prostate cancer in people
who have no signs of cancer. The estimated benefit of this testing is that for
every 1000 participants; about one individual will avoid death from cancer.
In saving this individual, 50 will undergo treatment for a cancer that was
not going to cause them problems. About half of the individuals
undergoing treatment (25) will have difficulty controlling their bladder
and/or maintaining erections for several years.
Providing information like this to a patient will help make a better decision about whether or
not PSA testing is appropriate for him. Unfortunately, this information is not routinely
available. It remains unclear to what extent a patient is truly autonomous or well informed, in
34
the absence of a basic level of information about the screening procedure, its harms and its
benefits.
35