Download Advanced prostate cancer optimising and integrating care

Payne Conf Rep Advanced Prostate Cancer_Layout 1 17/01/2013 14:48 Page 1
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Advanced prostate cancer –
optimising and integrating care
HEATHER A. PAYNE, CHRIS FARNHAM, MIKE KIRBY AND JANIS TROUP
The British Uro-oncology Group was formed
in 2004 as a professional association with
the specific aim of providing a network for
doctors working in uro-oncology.
Heather A. Payne, MB BS, FRCP, FRCR,
Consultant Clinical Oncologist, University
College London Hospitals; Chris Farnham,
MB BS, BSc, FRCP, Consultant in Palliative
Medicine, St John’s Hospice, London;
Mike Kirby, MB BS, LRCP, MRCS, FRCP, GP
and Visiting Professor, Faculty of Health
and Human Sciences, University of
Hertfordshire and the Prostate Centre,
London; Janis Troup, BA(Hons), British
Uro-oncology Group Secretariat, London
www.trendsinurology.com
This report summarises discussions led by specialists in
secondary, primary and palliative care during a series of four
regional meetings organised by the British Uro-oncology
Group in partnership with Macmillan. The aim of these
meetings was to debate appropriate pathways of care for
patients with advanced disease, focusing on sequencing of
therapy and palliative care. They also provided a forum to
increase awareness and understanding across professional
disciplines of NHS reforms and commissioning processes in
the field of prostate cancer.
rostate cancer remains the most
commonly diagnosed malignancy in
men in the UK and accounts for a quarter
of all reported new male cancers. In 2009,
40 841 new cases of prostate cancer were
reported.1 It has been estimated that
around 10 per cent of these will be men
presenting with advanced or metastatic
disease. In addition, there will be other
men who relapse and progress to
develop advanced disease following
therapy for localised or locally advanced
prostate cancer.
P
The optimal management of men with
advanced prostate cancer is an increasingly
complex process, with a variety of available
treatments and involvement of many
different disciplines spanning primary,
secondary and palliative care.
Prostate cancer patients spend longer
undergoing palliative care than most other
cancer patient groups. This necessitates a
greater emphasis on the treatment of
disease progression and end-of-life care.
THERAPY FOR ADVANCED DISEASE
Hormone therapy continues to play a
pivotal role in the management of
advanced prostate cancer. Huggins and
Hodges first recognised the role of
testosterone suppression to treat prostate
cancer in the early 1940s2 and introduced
the concept of androgen deprivation
therapy (ADT). Surgical castration was
established as an effective management
of advanced prostate cancer by not only
reducing the painful symptoms of the
disease but also slowing the overall
cancer progression. Although an effective
therapy, the surgical approach had an
understandable psychological impact on
many men.
Medical castration in the form of the
luteinising hormone-releasing hormone
(LHRH) agonists was developed in the
1980s and was shown to be as effective
as surgical castration.3 Response rates of
over 85 per cent are anticipated for up to
three years.4 The Medical Research Council
study of immediate versus delayed ADT for
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advanced prostate cancer demonstrated
significant advantages for early castrationbased treatment.5 Delayed hormone
therapy resulted in a significantly higher
risk of pathological fracture, spinal cord
compression, ureteric obstruction and the
development of extraskeletal metastases.
These findings support the introduction
of hormones before symptomatic
progression for first-line therapy. This
concept could also be applied to the
addition of later treatments as part of a
sequential approach in order to maximise
quality of life and reduce the burden of
symptomatic therapies.
In spite of encouraging initial responses to
LHRH agonists, the majority of men with
advanced prostate cancer eventually
become refractory to ADT, ultimately
developing progressive disease. The optimal
management of metastatic hormonerefractory prostate cancer (mHRPC)
remains uncertain, but there is an
increasing number of therapy options
for use on a sequential basis. The order
and combination of therapies may depend
upon the patient’s age, performance status,
relevant comorbid conditions, prostatespecific antigen (PSA) kinetics or site
of progression and whether or not this
is symptomatic.
The term ‘castration-resistant prostate
cancer’ (CRPC) refers to progressive disease
in spite of castrate levels of serum
testosterone (<50ng/dl or <1.7nmol/l).
CRPC is a term now frequently used in
preference to mHRPC. Unlike mHRPC,
which is resistant to all further hormonal
manipulation, mCRPC can remain hormone
sensitive, and indeed may be supersensitive
to very low levels of androgen. As such,
continued androgen deprivation with LHRH
agonists, the addition of antiandrogens to
achieve combined androgen blockade,6 or
further hormonal manipulation with
antiandrogen withdrawal,7 oestrogens8 or
corticosteroids such as dexamethasone
0.5mg,9 may all represent effective further
treatment strategies.
TRENDS IN UROLOGY & MEN’S HEALTH
Chemotherapy has been used as treatment in
mHRPC for many years. Historically, the most
commonly used combination was with
mitoxantrone and prednisolone, which
provided some palliation of painful symptoms,
but did not demonstrate any improvement in
PSA response or survival in a randomised
study against prednisolone alone.10
The results of randomised studies using
the chemotherapy agent docetaxel
have led to a renewed interest in
chemotherapy in recent years. The Tax 327
study11 demonstrated that docetaxel in
combination with prednisolone was the
first chemotherapy agent not only to
improve quality of life but also to
increase overall survival at three years
(18.6 versus 13.7 per cent) when compared
to the mitoxantrone and prednisolone
combination in a randomised trial of
men with mHRPC.
Chemotherapy may be administered as
second-, third- or fourth-line treatment
for mCRPC, depending on disease
characteristics and patient performance
status and comorbid conditions, with the
aim of preventing toxicity from disease
progression. The subsequent treatment
options were rather limited for men who
relapsed after docetaxel, and management
at that stage often involved symptomatic
palliative care only. However, in 2010 two
large multicentre randomised phase 3 trials
reported significant survival advantages for
men with mCRPC who had progressive
disease following docetaxel chemotherapy.
The first of these new therapies was
cabazitaxel, a novel taxane that was
developed to overcome docetaxel
resistance. The TROPIC study12
demonstrated a 30 per cent survival
benefit for cabazitaxel compared with
mitoxantrone when used as second-line
chemotherapy in patients progressing
during and after docetaxel treatment.
In addition, cabazitaxel significantly
improved progression-free survival
(PFS), tumour response and PSA response,
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and was as effective as mitoxantrone in
relieving pain.
Abiraterone acetate is an oral hormonal
agent that is a specific inhibitor of CYP17,
which is key to androgen and oestrogen
synthesis. In clinical trials, abiraterone
acetate showed an overall survival benefit
of 36 per cent over placebo in mCRPC
progressing after docetaxel.13 There was an
additional significant improvement in PFS,
PSA response and quality of life. These
results confirm the continued dependency
of mCRPC on the androgen receptor
signalling pathway.
These two new therapies will change the
sequencing of therapy for mCRPC and
there are many other promising
compounds in late-stage studies that (it is
hoped) will be added to the sequential
therapy in the future. These compounds
include: enzalutamide (MDV3100; a novel
antagonist of the androgen receptor),
TAK 700 (selective non-steroidal androgen
synthesis inhibitor of the 17,20 lyase
enzyme) and custirsen (an antisense
oligonucleotide targeting clusterin).
For many men with advanced prostate
cancer, active sequential therapies can be
the optimal form of palliation; in spite of
any associated toxicity, these agents can
offer prolonged periods of remission,
overall reduction in cancer-related
symptoms and a better overall quality of
life. Education of patients and healthcare
professionals outside of the specialist team
is essential to encourage early referral via
the multidisciplinary team to oncology
services so that all men have equal
opportunities to these new compounds
where appropriate. Equally early and
appropriate referral to palliative care
services is critical to ensure patients’ needs
are met throughout the care pathway.
PALLIATIVE CARE AND PROSTATE CANCER
As more treatment options for advanced
disease emerge, the role of palliative care
will ultimately evolve. Now, more patients
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are being diagnosed with advanced disease
at a younger age, which means their needs
and type of care will be different from
those of an older population.
factor for him if the palliative care team
have that time to work with him and
prepare him in the best possible way for
his departure.
Professional attitudes, opinions and service
provision are highly variable around the UK
in terms of palliative care support – the
important factor is accommodating care to
individual cases at the point where the
patient will benefit most.
The palliative care team uses guidance
documents, such as Advance care
planning, Preferred place of care and
Preferred place of death, to work with the
patient to improve his end-of-life care.14
However, this guidance can be effectively
implemented only if there is sufficient
time to organise the care of the patient’s
preference. For example, relocation,
allowing the patient to be comfortable
and die at home, can take months.
There is an ever-increasing need to
improve communications between
palliative care specialists and other
healthcare professionals involved in the
management of patients with advanced
disease. Some clinicians are recommending
that palliative care specialists could be
involved at a much earlier stage in the
patient pathway.
Planning by other primary and secondary
care professionals for palliative care support
for the patient and their family is critical.
Referrals to palliative care are often delayed
because of the stigma around the term
‘palliative care’ for patients, combined with
the fact that other healthcare professionals
are not always clear on a reasonable timing
around when to refer. Ideally, referrals to
palliative care should be considered where it
is felt the patient may have an anticipated
one-year survival.
This optimum timing of referral allows the
palliative care team to start talking to
patients and their family, relatives and
carers about the ‘D’ word and planning
their care leading up to their death. There
is a sensitivity with which palliative care
specialists are able to approach patients
and families, and their involvement should
not be deferred out of a fear of causing
distress to patients or families.
The overriding role of palliative care on the
physical side is to make the patient as
comfortable as possible; namely, having
access to the right drugs at the right time
in the place where they need them and
can access them. This allows pain to be
managed appropriately, particularly if a
patient’s wish is to die at home.
On the psychological and spiritual side it is
often more problematic. There is no easy
treatment for a young man dying of
mCRPC who will leave his children and
spouse; there is no cure for making him
feel better. Time can, however, be a helping
www.trendsinurology.com
commissioning services – and it is
important to ensure that this is in the best
interests of the patients.
With all aspects of life and death, cost is
a limiting factor for optimum service
delivery, yet the more palliative care
specialists understand about the patients
at an earlier stage in the continuum and
the more uro-oncology or primary care
professionals understand about the
potential role of palliative care, the greater
the benefits should be for improving
patient care.
PRIMARY CARE AND COMMISSIONING
OF SERVICES
Within the NHS, the pace of change and
complexity has provided primary and
secondary care with huge challenges
and difficulties (Box 1). Lack of good
communication has made it difficult to achieve
a meaningful improvement in patient care.
Healthcare professionals need time and
support to understand the NHS reforms,
and this can detract resource away from
effective patient care. Primary care is
expected to play an increasing role in
There will be ongoing importance placed
on integrated care pathways for all
conditions, but in the case of prostate
cancer this is of critical value, given the
complexity of the disease and the pace of
introduction of new treatments.
The NHS Quality, Innovation, Productivity
and Prevention agenda is designed to
produce cost-efficiency savings while
driving up quality (alternatively interpreted
as better quality for the same money!).
This will involve integrated care pathways,
reductions in unplanned care, cost
containment, cost avoidance and efficient
GP commissioning.
The implications of all this for cancer care
are significant. Cancer networks will now
be maintained beyond 2013 and the NHS
Commissioning Board will host and
support cancer networks on a continuing
basis to improve outcomes for cancer
patients. The document Improving
outcomes: a strategy for cancer15
provides possible future models for the
delivery of advice and support on cancer
commissioning at the national level, in
particular, by exploring ways in which the
National Cancer Action Team and cancer
networks might best offer their support to
providers and commissioners through a
more flexible, social enterprise-based
approach. Integrated care pathways will
increase urology and oncology joint
working and will help to define choice of
treatments. These pathways will need
to allow for the introduction of new
treatments and be flexible and simple for
the commissioning groups to understand.
For patients with CRPC, new treatments
will not always be approved by NICE
(whose role is changing), the Scottish
Medicines Consortium or health boards,
which means that healthcare professionals
are left with their hands tied or are
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BOX 1. Pace of change within the NHS
2001: SHIFTING THE BALANCE OF POWER
l Match service to patients’ needs, not vice versa
l Optimise care in the optimum settings
l Local commissioning
l Ensure the best NHS skill mix
l Reward performance
2003: THE NEW GMS CONTRACT
l Improve the health of the community
l Integrate health and social care
l Secure the provision of services through commissioning and primary care
trusts
l A new competitive environment where ‘patients matter’
2004: HARNESSING THE POWER OF THE PRIMARY CARE FRONTLINE
(THE KING’S FUND)
l The benefits of practice-led commissioning
l What it could mean within the new NHS structures
l How to implement practice-led commissioning
2004: NHS IMPROVEMENT PLAN
Priorities for the NHS between 2004 and 2008
l Supporting the ongoing commitment to a 10-year process of reform first set
out in the NHS Plan
l Guidance on how to achieve a truly patient-led NHS
2005: DELIVERING THE NHS IMPROVEMENT PLAN
l How to deliver the improvement plan, explaining the fundamental change in
relationships with patients and the public
l From a service that does things to and for its patients to one that is patient
led, where the service works with patients to support them with their health
needs
2010: EQUITY AND EXCELLENCE: LIBERATING THE NHS
l How patients should be at the heart of everything the NHS does
l A focus on continually improving those things that really matter to patients
– the outcome of their healthcare
l Empowering and liberating clinicians to innovate, with the freedom to focus
on improving healthcare services
expected to seek other routes for accessing
treatment options for men with advanced
disease. In England, the use of the Cancer
Drugs Fund is a highly topical issue and
indeed has been an effective system in
allowing appropriate patients access to
new treatments in this field where
technology bodies have proved an obstacle.
TRENDS IN UROLOGY & MEN’S HEALTH
THE CHALLENGES AHEAD
More than 100 healthcare professionals
and managers participated in the meeting
series, contributing actively to the debate
and discussion around how best to
improve the care of men with advanced
prostate cancer. Defined strategies for
improvement in service delivery will
JANUARY/FEBRUARY 2013
be an ongoing subject for the British
Uro-oncology Group to address in future
activities. In the meantime, the challenges
facing all those involved in advanced
prostate cancer management are
summarised in Box 2. Of paramount
importance is improved communication
between all disciplines caring for these
patients and access to the increasing range
of treatment options.
The impact on the healthcare economy
through the additional cost of these
treatment options and the increased
impact on cancer services will also need to
be addressed as we move forward into an
exciting new era in the management of
advanced prostate cancer.
Declaration of interests
Heather Payne has attended and received
honoraria for advisory boards and served
as a consultant for AstraZeneca, Janssen,
Johnson and Johnson, Sanofi, Takeda,
Amgen, Ferring and Novartis. Chris Farnham
has attended and received honoraria for
advisory boards and educational meetings
from AstraZeneca, Janssen and Sanofi.
Mike Kirby has received funding from the
pharmaceutical industry for research, lecturing,
conference attendance and advice. The British
Uro-oncology Group meeting series was
funded by an educational grant from Sanofi,
but the company had no influence over the
content of this article.
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Cancer Research UK. Prostate cancer incidence
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1.
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BOX 2. Challenges in improving the management of advanced prostate cancer
10.
l What protocols should be used? Do they exist?
– When should men with castration-resistant prostate cancer be referred to
an oncologist?
– Should urologists start maximum androgen blockade first and then refer
when this fails?
– Variability of prognosis in metastatic disease: where does palliation begin?
– Maintaining contact and communication with patients after hospital
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discharged
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and oncologists
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patients appropriate for GP and those for hospital/occupational health
l Equality in accessing specialist services
l Accessing new drugs for prostate cancer
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prednisone (P) improves overall survival (OS) in
patients (pts) with metastatic castration
resistant prostate cancer (mCRPC) who have
progressed after docetaxel-based chemotherapy
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