Transcript The Investigation of a Patient with Cancer

The Investigation of a Patient with Cancer –
General Aspects
Alastair J Munro
August 2009
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Key points in the investigation of a patient with cancer
before we can make rational decisions about which
treatments to deploy we need to know:
where the disease is, how much disease there is at each site and what
the behaviour of the disease is likely to be:
this is clinico-pathological staging (TNM and other staging systems)
it allows us not only to select treatment that is appropriate, it also enables us to
estimate the likely outcome and prognosis –information of crucial importance to
patients and their families.
how fit the patient is, how able are they to withstand potentially toxic
treatments
this concerns performance status, co-morbidity, current drug therapy and
assessment of risk factors for complications of treatment
what the patient’s attitude is to their illness – are they keen to be
managed actively or is their attitude somewhat more passive?
this information is less easy to obtain and involves careful discussion with patients
and, most importantly, giving the an opportunity to express their views and
preferences in an environment that does not make them feel rushed or pressured
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Investigations in Patients with cancer
This list of tests and investigations is by no means comprehensive, nor does every
patient with cancer require all the items.
Clinical history and examination
Assessment of Performance Status and co-morbidity
Tumour markers
Histopathology including tumour grade
Imaging
Plain X-ray
Contrast studies
Ultrasound
CT (computerised axial tomography)
MRI (magnetic resonance imaging)
PET (positron emission tomography) etc
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How cancer spreads
The ability to invade into local organs and tissues is
characteristic of cancer (invasion)
The ability to spread widely throughout the body is also
characteristic (metastasis)
The spread of cancer can be mapped out, based on a
knowledge of the likely patterns of spread
This process of mapping out is known as staging
There is a variety of different staging systems, some of which
are specific to particular types of cancer (such as the Ann
Arbor system for lymphomas). The TNM system and the AJC
systems cover most tumours and are the most widely used
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TNM staging system
This is an internationally agreed staging system for cancer which has been
developed under the auspices of the UICC (International Union Against
Cancer)
It defines 3 components of importance:
T stage : the extent to which a tumour has spread locally
N stage: the extent to which a tumour has spread to the lymph glands in
the vicinity of the tumour (the regional nodes)
M stage: the extent to which the tumour has disseminated (metastatic
disease)
It also includes an R component (which indicates – where appropriate – the
amount of disease persisting after surgery
The system is regularly updated and altered: the current edition is the 6th
(from 2002)
The system is compatible with other staging systems such as the AJC (since
1987) and the FIGO system for staging gynaecological tumours
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TNM in practice – colorectal cancer
Primary Tumour (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumour
Tis: Carcinoma in situ: intraepithelial or invasion of the lamina propria*
T1: Tumour invades submucosa
T2: Tumour invades muscularis propria
T3: Tumour invades through the muscularis propria into the subserosa, or into nonperitonealized pericolic or perirectal
tissues
T4: Tumour directly invades other organs or structures, and/or perforates visceral peritoneum
Regional Lymph Nodes (N)
NX: Regional nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in 1 to 3 regional lymph nodes
N2: Metastasis in 4 or more regional lymph node
Distant metastasis (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
Residual tumour following surgery ®
RX = Presence of residual tumour cannot be assessed
R0 = No residual tumour
R1 = Microscopic residual tumour
R2 = Macroscopic residual tumour
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TNM in practice –
Glottic cancer (cancer of the vocal cords)
T1
Tumour limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility
T1a
Tumour limited to one vocal cord
T1b
Tumour involves both vocal cords
T2 Tumour extends to supraglottis and/or subglottis, or with impaired vocal cord mobility
T3 Tumour limited to larynx with vocal cord fixation
T4a Tumour invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of neck
including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
T4b Tumour invades prevertebral space, encases carotid artery or invades mediastinal structures
Nx
N0
N1
N2
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple
ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more
than 6 cm in greatest dimension
N2a
Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension
N2b
Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2c
Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3 Metastasis in a lymph more than 6 cm in greatest dimension
Mx Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
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AJC system
The AJC (American Joint Committee) staging system has, since
1987, used the same TNM categories as the TNM (UICCC)
system
The main contribution of the AJC system is that it places
combinations of T, N and M into prognostically relevant
groupings – this deals, in part, with a problem that is intrinsic
to the TNM system: the large number of possible TNM
combinations for each tumour site.
The AJC stage groupings for colorectal cancer, together with
the corresponding 5-year survival data, are shown on the next
slide.
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AJC Stage and Survival – Colorectal Cancer
AJC Stage
TNM
% 5-year survival
I
T1 or T2, N0 M0
93.2%
IIa
T3 N0 M0
84.7%
IIb
T4 N0
72.2%
IIIa
T1 or T2, N1 M0
83.4%
IIIb
T3 or T4, N1 M0
64.1%
IIIc
Any T, N2 M0
44.3%
IV
Any T, Any N, M0
8.1%
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Stage Shift
How to improve the outcome of cancer management
without really trying
The Will Rogers Phenomenon
“when the Okies moved to California they raised the
intelligence levels in both states”
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The arithmetic of stage shift
Before new staging test
Stage
distribution cure
Number Stage
rate
cured
After new staging test
distribution cure
number %"improvement"
rate
cured
in cure rate
I
80.0%
90.0%
72
I
50.0%
94.0%
47
4.0%
II
5.0%
80.0%
4
II
8.0%
87.5%
7
7.5%
III
5.0%
80.0%
4
III
12.0%
83.3%
10
3.3%
IV
10.0%
50.0%
5
IV
30.0%
70.0%
21
20.0%
All
100.0%
85
All
100.0%
85
0%
History
The patient’s account of the history of their clinical problems
is important because:
It gives the patient an opportunity to tell their story in their own
words
gives the message that attention will be paid
allows patient to indicate what their priorities might be
facilitates the development of a trusting relationship between clinician and the
patient
allows for estimate of duration of illness before diagnosis
Permits an exploration of problems not directly related to cancer, but
which may affect its management
other illnesses and treatments (e.g. cardiac problems)
co-existent medical problems are often referred to as “co-morbidities”
financial and social issues of concern to the patient
extent and scope of family and social support
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Clinical examination
Despite the investigative technologies available to modern
clinicians the physical examination of the patient is still
relevant and important
it permits an overall assessment of physical fitness
this can be formally recorded as “performance status”
it may disclose other unsuspected but relevant problems, e.g. a heart
murmur
it may identify spread of disease that imaging failed to demonstrate
e.g. lymph node enlargement in a region that was not included in the
routine scanning procedures
it is important part of the therapeutic relationship that is established
between patient and clinician (the laying on of hands)
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WHO scale for assessing Performance Status
0 - Asymptomatic (Fully active, able to carry on all pre-disease activities
without restriction)
1 - Symptomatic but completely ambulatory (Restricted in physically
strenuous activity but ambulatory and able to carry out work of a light or
sedentary nature. For example, light housework, office work)
2 - Symptomatic, <50% in bed during the day (Ambulatory and capable of all
self care but unable to carry out any work activities. Up and about more
than 50% of waking hours)
3 - Symptomatic, >50% in bed, but not bedbound (Capable of only limited
self-care, confined to bed or chair 50% or more of waking hours)
4 - Bedbound (Completely disabled. Cannot carry on any self-care. Totally
confined to bed or chair)
5 - Death
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Co-morbidity
Co-morbidity is defined as the presence of pre-existing or coexisting illness, unrelated to the cancer itself
Co-morbidity will influence decision-making but will also have
a more direct effect upon outcome
Mechanisms will include
effects on fitness for anaesthesia and major surgery
patients unfit for major surgery may be treated with radiotherapy
interactions with drugs used for treating cancer
e.g. capecitabine and coronary artery disease
effect on fitness for radiotherapy
e.g. severe COPD unable to lie flat for treatment
competing cause of death
e.g. severe coronary artery disease and uncontrolled angina may make discussions
about adjuvant treatment irrelevant in a patient whose heart disease is likely to kill
them within a few months
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Listening to patients and their families
Good communication between patients, their families and clinicians is,
if cancer is to managed effectively, essential.
Communication is not just about clinicians giving information to
patients.
Patients and their families can provide vital information that can affect
the decisions that are made about how best to manage the disease
If patients’ views and opinions are not taken into account in the
decision-making process then this violates the ethical principle of
autonomy
Patients are rarely present at MDT meetings and this, for the reasons
summarised above, may compromise the validity of decision-making
If the best interests of patients are to be represented at MDT meetings
then firstly, someone needs to listen to them, and, secondly, that
individual needs to be able to give an account of the patient's views
and opinions to the MDT meeting.
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The principles of diagnostic testing
The tests we use in clinical medicine are not infallible
All tests bring with them the possibility of false
negative and false positive results
There are algebraic methods that can be used to
assess the performance of any given test
One of the key influences on the performance of any
diagnostic test is the likelihood that the condition
being tested for is actually present
the performance of a test will change according to clinical
circumstances
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The algebra of testing
by convention the disease present/test positive cell is always placed at the top left
of the table
the percentage of patients who have the disease present and whose test result is
positive is given by a/(a + c) : this is the sensitivity of the test (other names include
TPR, for true positive rate, and PiD, for positive in disease). The false negative rate
(FNR) is equal to 1 - sensitivity: the FNR indicates the proportion of patients whose
test is negative, but who actually have disease.
the percentage of patients who do not have disease and who have a negative test is
given by d/(b + d) and is termed the specificity of the test (other names include
TNR, for true negative rate, and NiH, for normal in health). The false positive rate
(FPR) is given by 1 - specificity
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Prevalence and predictive value
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A useful nomogram
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A useful nomogram
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Tumour markers
A tumour marker is a test, performed on blood, urine or other
easily available fluid that reliably indicates whether or not a a
patient has cancer and, if cancer is present, gives an indication
of the amount of disease.
The ideal tumour marker is 100% specific and 100% sensitive
There is no ideal tumour marker
Clinically useful tumour markers include: α-fetoprotein (AFP); βsubunit of human chorionic gonadotrophin (βHCG); carcinoembryonic antigen (CEA); prostate-specific antigen (PSA).
Estimations of tumour marker levels are an essential part of the
management of germ-cell tumours and choriocarcinoma. Their
role in the management of other solid tumours is less well
defined.
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