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PROSTATE diSEASE
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A tale of four prostates
ROGER KIRBY, DAMIAN HANBURY, JOHN ANDERSON AND SEAN G. VESEY
Four urologists relate
their personal experiences
of prostate cancer and
highlight some important
learning points.
uring the past two years, rather ironically,
all four authors of this article, each a busy
urologist in practice with an interest in prostate
cancer, have themselves been diagnosed and
treated for prostate cancer. Rather than hush
it up, as if it were a dark secret, we decided
that there would be some merit in terms of
education, debate and awareness, if we were to
make public the presentation and treatment of
each of our four individual cases.
D
CASE 1: ROGER KIRBY
Roger Kirby, aged 61, an otherwise
fit, asymptomatic individual who
had measured his prostatespecific antigen (PSA) for more
than a decade, noticed a gradual
rise in PSA to 4.4ng/ml. 3-Tesla
magnetic resonance imaging
(MRI; Figure 1) revealed a
suspicious focus in the right
peripheral zone adjacent to but
not penetrating the capsule.
Figure 1. 3-Tesla magnetic resonance image
Transrectal ultrasound (TRUS)of the prostate showing a suspicious focus in
guided biopsy confirmed Gleason the right peripheral zone adjacent to but not
3+4=7 adenocarcinoma in three
penetrating the capsule
out of 12 cores. A bone scan was
negative. A robotically assisted radical prostatectomy was performed, by
Professor Dasgupta, without complications. Pathology confirmed complete
excision of a Gleason 4+3=7 1.3cc tumour with invasion of the capsule but
negative surgical margins. Recovery has been uneventful.
LEARNING POINTS
There are more than 1000 urologists presently
practising in the UK. As there is a one in nine
lifetime chance of being diagnosed with
prostate cancer, the fact that there are at least
four working urologists currently afflicted by
the disease is probably not surprising. The four
cases summarised here illustrate several
important aspects of the management of
prostate cancer, an area of medicine that is
currently changing very rapidly.1
fact, thanks to the work of Parker3 and Klotz,4
and the publication of the NICE guidelines5 on
prostate cancer, the majority of patients with
low-risk, Gleason pattern 3+3=6 prostate
cancer are now managed by active surveillance
rather than by surgery or radiotherapy.6
The first case (RK) illustrates the value of early
detection using serial PSA testing in terms of
diagnosing prostate cancer, while it is still
confined within the capsule of the gland, and
therefore potentially still curable. The results
of the European Randomized Study of
Screening for Prostate Cancer (ERSPC)2
confirm that mortality from prostate cancer
can be reduced by early detection, but the
authors worry that the lives saved will be
counterbalanced by those low-risk cases
identified who are at risk of ‘overtreatment’. In
A second learning point from this case is
the value of high-resolution 3-Tesla MRI
scanning, with gadolinium enhancement, in
identifying suspect areas within the gland
that can be targeted by either transrectal or
transperineal ultrasound-guided biopsy (see
Figure 1). Comparison of the preoperative
MRI scan with the prostate itself after
robotic surgery confirms the accuracy of this
technology in localising the tumour. This in
turn aids the surgeon in achieving negative
surgical margins.
TRENDS IN UROLOGY & MEN’S HEALTH
MARCH/APRIL 2013
Go to the Trends website to view a
video debate on this subject with
Roger Kirby, Damian Hanbury and
John Anderson: [URL to be added
when available]
Roger Kirby, MA, MD, FRCS(Urol), FEBU,
Director, The Prostate Centre, London;
Damian Hanbury, MS, FRCS(Urol),
Consultant Urologist, The Lister Hospital,
Stevenage, Herts; John Anderson,
MB ChB, ChM, FRCS, Consultant Urologist,
Royal Hallamshire Hospital, Sheffield;
Sean G. Vesey, FRCS, FEBU, Retired
Consultant Urologist, Southport and
Ormskirk Hospital NHS Trust, Merseyside
www.trendsinurology.com
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CASE 2: DAMIAN HANBURY
Damian Hanbury, aged 55, a busy urologist in Hertfordshire, presented in
2010 with worsening lower urinary tract symptoms of frequency and poor
flow. A PSA measurement came back at 29ng/ml. Biopsy confirmed
Gleason 4+4=8 adenocarcinoma and an MRI suggested locally advanced
disease. There was a single suspicious focus in the pelvic bone on both
MRI and bone scanning. A decision was made to proceed with androgen
ablation followed by external beam radiotherapy to include the presumed
metastatic focus in the pelvis. Two years on, his PSA remains undetectable
at 0.06ng/ml.
The second case (DH) illustrates the not
uncommon dilemma of whether to use
external beam radiotherapy in addition to
androgen ablation when there are equivocal
skeletal or soft tissue lesions, which may or
may not represent metastatic disease. In
this case there was a biopsy-proven locally
advanced disease involving the prostate,
which was responsible for the lower urinary
tract symptoms, and a lesion within the
CASE 3: JOHN ANDERSON
John Anderson, aged 58, a urologist from Sheffield and President Elect of
the British Association of Urological Surgeons, was perfectly well and
without symptoms in early October 2011, and had a routine PSA test,
which came back at 1.7ng/ml. On 27 January 2012 (only four months
later) he felt a mass in the upper abdomen and a computed tomography
(CT) scan confirmed multiple liver metastases with no other detectable
abnormality. With a normal PSA four months earlier, no urinary symptoms
and no extrahepatic disease visible on the scan, the possibility of this
being related to the prostate never really crossed anyone’s mind. A
couple of weeks later, a liver biopsy confirmed a poorly differentiated
adenocarcinoma. Subsequent immunohistochemistry of the liver biopsies
stained positive for PSA, which confirmed the diagnosis of metastatic
prostate cancer. It was only then that the serum PSA was measured,
which had risen from normal 1.7 to 92.7ng/ml in four months.
Androgen deprivation therapy resulted in a PSA nadir of 0.2ng/ml
after four months of treatment, but the PSA then started to climb. In
November, he developed sudden-onset severe right-sided abdominal pain
requiring opiates to control symptoms. A further CT still showed no
evidence of disease outside of the liver, although the liver metastases had
increased considerably in size and were considered the likely explanation
for the pain. The PSA at this time was 483ng/ml. In view of the symptoms
and progressive disease, docetaxel-based chemotherapy was commenced.
After two cycles the pain has improved significantly, the PSA has fallen
somewhat and he is back playing golf. The side-effects from the
chemotherapy are not too bad, other than he has lost his taste for white
wine! Abiraterone/enzalutamide are further treatment options if there is
further disease progression.
www.trendsinurology.com
pelvic bones, which may or may not have
represented a metastasis. Fortunately, this
area could be encompassed in the external
beam radiotherapy field, which was used to
treat the primary lesion.
Case 3 (JA) is most unusual in presenting
with liver metastases, in spite of a normal
PSA only a few months before and no
other evidence of disease elsewhere. It
does illustrate how the PSA level can be
misleading, in spite of quite large-volume
metastases, especially in very poorly
differentiated tumours. Hormonal therapy
produced a useful but relatively short-lived
response, and fortunately taxane-based
chemotherapy seems to be producing a
second remission.
The final case (SV) illustrates the not
uncommon presentation of locally advanced
disease with lymph node metastases and the
subsequent development of symptomatic
bone metastases requiring local radiotherapy
to resolve. A combination of androgen
ablation with taxane-based chemotherapy
and additional abiraterone7 has produced a
prolonged response. The new oral agent
enzalutamide,8 which has produced
impressive results in clinical trials, and
the encouraging clinical profile of the
alpha-pharmaceutical Alpharadin,9 are likely
to be the next therapeutic options.
DISCUSSION
Anxieties about overtreatment of low-risk,
low-volume Gleason 3+3=6 prostate cancers
have fostered the myth that prostate cancer
is somehow a toothless tiger. Consideration
of the four clinical situations above, drawn
from the ranks of actively practising
urologists, clearly illustrates that this is not
always the case.
Progress with treatment is being made with
kinder, minimally invasive, robotically
assisted surgery and better targeted, more
powerful radiotherapy. Androgen ablation
therapy still provides the mainstay of therapy
for metastatic disease, but abiraterone,
enzalutamide, Alpharadin and chemotherapy
TRENDS IN UROLOGY & MEN’S HEALTH
MARCH/APRIL 2013
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CASE 4: SEAN VESEY
4.
Sean Vesey, aged 58, a laparoscopic radical prostatectomist from
Merseyside, presented in early 2010 with left iliac fossa discomfort, which
prompted investigations, including a PSA. This came back at 78ng/ml.
His PSA had been just 1.4ng/ml some 18 months earlier. TRUS biopsy
confirmed T3b Gleason 4+3=7 adenocarcinoma in all cores and an MRI
revealed pelvic and para-aortic lymphadenopathy. Although the original
bone scan was clear, a subsequent bone scan at one year confirmed the
presence of bone metastases in the cervical and lumbar spine. Initial
hormonal therapy reduced the PSA to a nadir value of 8.9ng/ml. Three
cycles of chemotherapy followed by abiraterone further reduced the PSA
to 0.27ng/ml. Although currently well, local radiotherapy has been
administered to a new pelvic metastasis. The new agents, radium-223
chloride (Alpharadin) and enzalutamide are being considered, but
currently held in reserve.
with taxotere or cabazitaxel are all now
useful, evidence-based, second-line options
when hormone relapse occurs.10
One key question is whether or not we
should all carefully monitor our own, and our
patients’, PSA levels over time, and respond
to a rise by organising a 3-Tesla MRI and a
targeted biopsy of the prostate to achieve
early detection. In one of the four cases (JA),
the PSA was negative only a few months
before presentation; in another (SV), the PSA
rose from 1.4 to 78ng/ml over an 18-month
time frame. Clearly, annual PSA testing would
not have been helpful in either of these
situations. New, better ways are needed to
identify poorly differentiated, aggressive
prostate cancers as they often do not
manufacture and secrete PSA in their early,
potentially curative stages.
The debate about screening for prostate
cancer seems likely to run and run, especially
since the ERSPC2 reported a positive result,
while the US-based Prostate, Lung, Colorectal
and Ovarian (PLCO) cancer screening trial11
produced a negative one. To compound the
problem, while a Scandinavian study of radical
prostatectomy versus watchful waiting
revealed a survival advantage for patients
treated surgically,12 the US-based Prostate
Cancer Intervention versus Observation Trial
(PIVOT) showed no benefit.13
TRENDS IN UROLOGY & MEN’S HEALTH
MARCH/APRIL 2013
There is at last a realistic prospect for more
targeted screening of those most susceptible
to the disease.14 More than 30 prostate
cancer susceptibility genes have been
identified and it seems possible that men
unlikely to develop prostate cancer could be
excluded from screening protocols and
instead attention focused on those most
likely to develop the disease.
Much remains to be done to improve
awareness about the risks of prostate cancer,
among not only urologists, but also family
practitioners and the general public.
Although screening is still controversial,
better treatments for hormone-relapsed
disease are now becoming available. We
sincerely hope that the openness about our
own diagnoses and management will help to
dispel the taboo that still haunts this most
common of cancers of men.
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