The Investigation of a Patient with Cancer – General Aspects

1. The Investigation of a Patient with Cancer –General Aspects Alastair J Munro August 2009 alastair j munro e-lfh

2. 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 alastair j munro e-lfh

3. 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 alastair j munro e-lfh

4. 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 alastair j munro e-lfh

5. 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 alastair j munro e-lfh

6. 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 alastair j munro e-lfh

7. 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 Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension N2 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 alastair j munro e-lfh

8. 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 problemthat 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. alastair j munro e-lfh

9. AJC Stage and Survival – Colorectal Cancer alastair j munro e-lfh

10. 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” alastair j munro e-lfh

11. The arithmetic of stage shift

12. 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 alastair j munro e-lfh

13. 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) alastair j munro e-lfh

14. 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 alastair j munro e-lfh

15. Co-morbidity • Co-morbidity is defined as the presence of pre-existing or co-existing 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 alastair j munro e-lfh

16. 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. alastair j munro e-lfh

17. 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 alastair j munro e-lfh

18. 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 alastair j munro e-lfh

19. Prevalence and predictive value alastair j munro e-lfh

20. A useful nomogram alastair j munro e-lfh

21. A useful nomogram alastair j munro e-lfh

22. 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); β- subunit of human chorionic gonadotrophin (βHCG); carcino-embryonic 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. alastair j munro e-lfh