1

Oncology Core Cases

Cancer VC Lecture (Dr Kristen Auret - Monday 15
th
October 2007)

More info: http://nccam.nih.gov and www.cancer.gov/cancertopics/treatment/cam

Exams
Most questions focus on early stage of cancer
Usual format is to follow patient through presentation treatment supports
90% of cases require oncologist involvement so make sure you say refer to oncologist
OSCE:
o Has 1 cancer station usually a scenario
o Eg. Mr Jones presented 3 days ago with a lump, this is his CT scan, what do you think is wrong
and discuss treatment options

Things to Know
Need to know these for the common cancers:
o Colon, breast, prostate, lung
o Not mesothelioma and smaller malignancies
Staging (most are TNM, colon is Dukes)
Treatment options
o Intent/aim (below)
o Types radio, chemo, hormonal, palliative (know basic chemo regimes for common cancers)
o Alternative and complementary therapies
o Side effects generic and some specific
Response rates
o Dont need to know all specifically, but have some idea so you can counsel pnt about Rx options
Standard protocols, esp. for adjuvant treatment of
o Colon
o Breast
Basic idea of management for:
o Prostate
o Lung
Functional scales

Treatment
People are often fearful of chemo and radiotherapy, but not alternative treatments
Even elderly people are getting treated, as recent studies show that QOL is better in people who do
have treatment rather than those who dont, even in older people
Treatment regimes look at age and co-morbidities, to minimize S/E
Alternative medicine try to sell their products more
Find out response rates and side effect profile and discuss it in a knowledgeable way to make it
understandable to them

Complementary or alternative (CAM)
What is the difference between alternative and complementary?
o Complementary medicine - used in conjunction with medical and surgical (conventional)
treatment methods
eg. Brownes Cancer Centre at SCGH - Reiki, massage, reflexology
o Alternative - not used in conjuction with conventional therapies.
eg. Vit C injections, Selenium therapy
Where to find information and what are the options
Interaction with medical treatment
Where does info come from success rate in ethical trials

Aims of Treatment

1. Curative intent aim is to induce remission
2. Adjunctive
aim to consolidate and assist remission
- no visible tumour on imaging or biochemistry but treatment is given to consolidate
remission and prevent recurrence (eg. tamoxifem after breast lump removed)
- patient is in remission, ie. no visible cancer on scan and no increased tumour markers
3. Neo-adjunctive aim is to help remission by first making tumour smaller (eg. radio then surg)
4. Palliative intent
5. (not palliative care)
aim is to reduce the cancer load but not remove it
- radiotherapy and chemotherapy that is not aiming for remission/cure
- different to palliative care
6. Supportive aim is to relieve symptoms
7. Palliative care no treatment, aim is to just make them comfortable

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Side Effects
Generic side effects
o All cells that turn over quickly hair, nails, skin
o Neuropathy all cells that cant regenerate
Specific side effects
o Cisplatin
o 5-FU 5-fluorouracil
o Taxanes doxetacel
Generic:
o Bone marrow suppression neutropaenia, febrile neutropaenia, anaemia, thrombocytopaenia
Different drugs have different propensity for certain ones
o Nausea and vomiting
o Fatigue
o Alopecia not all chemotherapy but most
o GI upset, change in bowel habit
Diarrhoea fluorouracil
Constipation cisplatin
o Mouth ulcers
Mitoxantrone:
o Cardiotoxicities at determined point
o GI upset
o Rash
o Urine and sclera discolouration
o Others

Mx of nausea and vomiting
Ondansetron can be given IV, PO, sublingually. 5-HT receptor antagonist. Good for acute nausea.
Start IV with chemotherapy, then give for 3-5/7. Works well with dexamethasone.
Metoclopramide pro-kinetic and antinausea, acts on CNS nausea centre. Give PO, hour before
meals. Good for chronic control.
Stemetil also good for chronic control.
Other drugs, granisetron (Kytril), aprepitant for highly emetogenic chemotherapy, haloperidol.
Give a basal regime with extra top-ups if needed.
Give rectal suppositories, with gloves, in case nothing will stay down.
Do not accept any level of nausea treat in anticipation.

Tumour Markers
Relevant in symptomatic patient
- PSA
- OMMA, Ca-125
- Ca 19-9 (upper abdo visceral malignancies)
- NSE- Small Cell Lung Cancer

Organ Preservation Therapy
B12 and folate supplementation and if on methotrexate for mesothelioma
o To prevent peripheral neuropathy (due to depletion of vitamin B12)
B12 supplementation to prevent peripheral neuropathy
Ova and semen harvesting prior to commencing therapy (future fertility)
Hydration on cisplatin due to risk of renal failure
Phlebitis from injection site
Cardiac imaging before and during treatment

Function scales

ECOG = Eastern Cooperative Oncology Group

0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or
sedentary nature, e.g., light house work, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more
than 50% of waking hours
3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5 Dead


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Clinical trials define patients by ECOG score
Rarely have chemo if 5 (dead), 4 (completely bed-bound), 3 (bed-bound 50% of day)
o Dont tend to tolerate treatment well body too frail
o If 4 or 5 may kill them with chemo
o Unless v. chemo centred tumour (eg. small cell, leukaemia)

Kanoske: 0 to 100
0 = dead, 100 = fully functioning

Breaking Bad News
Give specific oncology information, not just generic info (eg. talk about lumps etc)
Make another appt
Write it down
Acknowledge person is in shock, but still outline treatment options
Multidisciplinary management is good.
Think about impact on mental health.
Patient may not remember anything from your consultation, except that they have cancer

SPIKES
S = "Setting"
Physical position of body (level with patient, lower if the patient is angry), body language and eye
contact (avoid when situation is "hot")
Listening Skills use of silence and pauses, use of patients own language as a bridge; appropriate use
of touch.

P = "Perception"
(i.e. patients perception of the current situation)
Note different ways of asking; note patients vocabulary and comprehension; also note denial if
present

I = "Invitation"
(Aim to get a clear invitation to the patient to share information)
Different ways of asking (eg "Are you the sort of person who..?)
Accept the patients right not to know.

K = "Knowledge"
(imparting information)
NB: Aligning = start at a place compatible with the patients current comprehension.
Use small chunks.
Use English not Medspeak.
Acknowledge all patients responses and tailor delivery of information appropriately to patients
responses

E = "Empathising and Exploring"
Acknowledge emotions and their origins patients and your own - and respond appropriately.
Explore, validate and empathise their emotional responses.

S = "Strategy and Summary"
Make a plan via explanation and collaboration. Summarise main areas.
Any questions for now? Contract for next contact.




4
AN INTRODUCTION TO CHEMOTHERAPY (from www.virtualcancercentre.com)

Cancer is a disease characterised by disturbances in cell survival, proliferation, and differentiation (maturation
of cells so they can carry out specified functions). Cancer cells have a special ability to rapidly proliferate
(often leading to the production of a tumour mass) and metastasise (or spread) to distant tissues.
Chemotherapy refers to the use of cytotoxic (cell killing) drugs in the treatment of cancer. Tumour cells are
more sensitive than normal cells to chemotherapeutic drugs because they are rapidly dividing cells.

Chemotherapy treatment disrupts the cell cycle in an attempt to cause enough changes in the cellular makeup
so that the cell cannot divide, or damages the cellular makeup enough to cause the cell to die. Some
chemotherapeutic agents are cell cycle specific (meaning they act on cells at a specific stage of growth and
division) while others can be given at any time in a cells life and cause these terminal changes.

Chemotherapy drugs are sometimes given with the intent to cure your disease. In other instances they may be
used after surgery to prevent recurrence or may be used as a palliative measure to control symptoms and
improve quality of life, rather than actually curing disease (if this is not possible).

Chemotherapy often requires a combination of a number of drugs in conjunction with other treatments such as
surgery and radiation therapy. Depending on the type of drug used, it may be administered by mouth,
intravenously or directly into the affected organ. Chemotherapy regimens vary greatly and may require several
cycles of treatment with drug-free periods in between. Your medical oncologist can provide detailed
information about the specific regimen recommended for you.

Chemotherapeutic Classes

There are five chemotherapeutic classes:
1. Chemotherapy Treatment with Alkylating Agents
2. Chemotherapy Treatment with Anthracyclines
3. Chemotherapy Treatment with Taxanes
4. Chemotherapy Treatment with Vinca Alkaloids and
5. Chemotherapy Treatment with Anti-metabolites


Chemotherapy Treatment with Alkylating Agents
Alkylating agents cause cell death by interacting with DNA during cell synthesis. DNA is the component of cells
containing all the genetic information the cell needs to grow, divide and function. The DNA is like the blue-
print of living cells and has a special helical ladder structure. Alkylating agents work by directly interacting
with exposed DNA and adding alkyl groups. The resulting permanent DNA damage ultimately results in death of
the cells.

Chemotherapy Side effects of Alkylating agents:
All alkylating agents depress bone marrow function and cause gastrointestinal disturbances such as nausea and
vomiting. As bone marrow is responsible for the production of red blood cells, white blood cells and platelets
when it is depressed symptoms of anaemia, infection and bleeding respectively, may occur. Therefore regular
monitoring of blood counts is required during treatment. Frequency and severity of most adverse effects
increase with increasing dose. With prolonged use, two serious and unwanted effects occur of sterility and
secondary malignancies have been reported with alkylating agents.

Cyclophosphamide (cycloblastin, endoxan) was the first clinically effective cancer chemotherapy agent and is
the most commonly used alkylating agent. As well as its anti-tumour effects, it also has immunosuppressant
activity as it also disrupts the function of lymphocytes (immune cells). Other alkylating agents include
chlorambucil (leukeran), carmustine, lomustine and cisplatin. The latter is sometimes classed as a platinum
compound and has been responsible for the massive advances in the treatment of testicular cancer as well as
being effective against a range of other cancers including lung, ovarian and head and neck cancers


Chemotherapy Treatment with Anthracyclines
Anthracyclines are cytotoxic (cell killing) antibiotics that are also non-cell-cycle specific chemotherapy agents.
They are probably amoung the most commonly used cytotoxic drugs. Many antracyclines also have
immunosuppressant activity.

Side effects of anthracycline use include:
Side effects of anthracycline use include:
Myelosuppression (bone marrow suppression) especially of white blood cells, but also of red blood
cells and platelets. These side effects of chemotherapy can be minimised with red blood cell and
platelet transfusions. In addition if you develop fever during treatment (febrile neutropenia) you
must see a doctor for careful management.
Increased risk of infection and bleeding.
Toxicity to the heart which may lead to arrhythmias. Damage may become permanent after
approximately one month of treatment especially if you have been previously exposed to these

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drugs. It is for this reason that doctors are often reluctant to prescribe anthracyclines if you have
been treated with them in the past.
Severe local reactions, including tissue necrosis (death) or extravasation (leakage of drug outside the
blood vessels).
Secondary malignancies.
"Radiation recall-" The recurrence of skin damage from previous radiotherapy.
Alopecia (hair loss)- This may be associated with significant effects on quality of life.
Nausea and vomiting.
Oral ulceration.

Doxorubicin (adriamycin) is an example of an anthracycline medication which is used in a variety of cancers
including affecting the breast, endometrium (lining of the womb), ovary, testicle, thyroid, stomach, bladder,
liver and lung, soft tissues and several childhood cancers. Epirubicin and mitozantrone are other examples of
anthracycline medications.


Chemotherapy Treatment with Taxanes
Taxanes are cytotoxic agents that work on a protein called tubulin found in the cytoplasm of cells. Tubulin is
needed for the production of microtubules which are essential in cell division. Microtubules help separate
chromosomes (agents carrying our DNA) when cells divide.

Taxanes are generally used when other chemotherapy regimens have failed. They tend to be effective against
ovarian, breast and lung cancers. Two taxanes are currently available in Australia namely, paclitaxel (Anzatax,
Taxol) and docetaxal (Taxotere). The former has been shown to have activity in a broad range of solid tumours.
Docetaxal is very similar to paclitaxal in terms of mechanism of action, metabolism, and elimination. It is
currently approved as second line therapy for advanced breast cancer and non-small cell lung cancer (NSCLC).

Side effects:
Taxanes cause bone marrow suppression like many other chemotherapeutic agents. The most common effect is
neutropaenia, which increases the chance of infection.

Other side effects include:
Nausea and vomiting- A variety of anti-emetic (anti-nausea) agents are available for patients
receiving chemotherapy to help control and even eliminate symptoms of nausea. Particularly useful
agents are a class of drugs called 5-HT3 antagonists such as ondansetron (Ondaz, Zofran) and
granisetron (Kytril injections and
tablets) combined with dexamethasone (steroid). Other anti-emetics include metoclopramide
(Maxalon) and domperidone (Motilium).
Diarrhoea
Mouth sores
Joint and muscle aches
Alopecia (hair loss)
Paraesthesia (abnormal sensation)
Mild allergic reactions (flushing, shortness of breath, urticaria (hives), rash)
Anaphylactic reactions
Injection site reactions

Due to these side effects, your doctor may treat you with steroids and/or anti-histamine drugs prior to
commencement of treatment. This helps to reduce some of the side effects and minimise any hypersensitivity
reactions.


Chemotherapy Treatment with Vinca Alkaloids
Vinca alkaloids act on a specific phase of the cell cycle called metaphase (M phase). They are another class of
anti-tubulin agents (along with the taxanes) and work by binding tubulin and inhibiting the production of
microtubules. This halts cell division and leads to cell death. Vinca alkaloids are used to treat both
haematological (diseases of blood cells such as leukaemias) and non-haematological (solid organ) malignancies.
There are four vinca alkaloids currently available namely vinblastine, vincristine, vindesine and vinorelbine
(Navelbine).

Side effects:
Vinca alkaloids cause a number of the common side effects seen with chemotherapy such as:
Nausea and vomiting
Hair loss
Mouth sores
Headache
Constipation

Vinblastine also causes bone marrow suppression like many other agents, resulting in increased bleeding,
infection and anaemia risk. In addition, vinca alkaloids can damage nerves. For example, vincristine may cause
numbness, sensory impairment, blurred or double vision and/or general weakness.

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Chemotherapy Treatment with Anti-metabolites
Anti-metabolites are molecules that have very similar structures to true proteins within cells. They are
therefore taken up by cells which cannot distinguish the drug from the real protein. Once inside the cell, anti-
metabolites interact with DNA and RNA like the normal protein would but due to slight variations in their
properties prevent the cell processes from continuing. Anti-metabolites therefore prevent normal proteins
from binding in the cell and halt normal function and division. In other words they mimic and interfere with the
binding of real proteins. Once again this leads to programmed cell death (apoptosis).

The molecules mimicked by anti-metabolites include folate, purine and pyrimidine. These agents seem to be
particularly important in DNA synthesis and cellular metabolism in cancer cells.


Folate antagonists
These agents mimic folate and enter the cell. They inhibit an enzyme called dihydrofolate reductase which is
needed in the production of amino acids and purine nucleotides, the building blocks of DNA, RNA and key
cellular proteins. Methotrexate is the main folate antagonist. It may be used in a variety of solid tumours and
haematological malignancies. In addition its immunosuppressant properties may be utilised in the treatment of
non-malignant conditions such as rheumatoid arthritis and psoriasis.

Side effects:
Methotrexate is very toxic at high doses, particularly to bone marrow and the digestive tract lining. Symptoms
of toxicity include:
Bone marrow suppression, including bleeding, anaemia and increased risk of infection
Nausea
Anorexia
Diarrhoea raging from mild to severe ulceration and bleeding

Methotrexate is often administered with leucovorin, which is an agent designed to reduce the anaemia and
toxicity to normal cells that often accompanies methotrexate therapy.


Purine antagonists:
Purine antagonists mimic the purines adenine and guanine, two of the bases that make up DNA. By mimicking
these molecules, purine antagonists block DNA synthesis and prevent cell division. Examples of purine
antagonists include 6-mercaptopurine (Puri-Nethol), 6-thioguanine, dacarbazine and fludurabine. Purine
antagonists are used for the treatment of acute leukaemias.

Side effects:
The side effects of 6-mercaptopurine are listed below which are similar to those seen with many other
chemotherapeutic agents. They are rare in children.
Bone marrow suppression, resulting in increased bleeding and infection risk
Mouth sores
Skin rash/acne
Mild nausea
Abnormal liver function
Hair loss

Anorexia, fever, fatigue/weakness and facial flushing can also occur with other purine antagonists than 6-
mercaptopurine.


Pyrimidine antagonists:
Pyrimidine antagonists mimic the pyrimidines cytosine and thymine, the other two bases making up nucleotides
and DNA. By mimicking these molecules, pyrimidine antagonists block DNA synthesis and prevent cell division in
a similar mechanism to purine antagonists. The pyrimidine antagonists include 5-fluorouracil (Efudix),
cytarabine, capecitabine (Xeloda) and gemcitabine (Gemzar).

5-Flurouracil has a major role in the treatment of gastrointestinal cancers. Capecitabine is an oral version of 5-
fluorouracil and is used in the treatment of metastatic colon cancer and metastatic or resistant breast cancer.
Cytarabine is used to treat leukaemias, and gemcitabine is used in solid cancers such as ovarian or in
combination with cisplatin to treat non-small cell lung cancer. As 5-fluorouracil is active against dividing cells,
it also kills healthy cells, which contributes to the following side effects:
Tiredness
Nausea and diarrhoea
Bone marrow depression that may lead to anaemia
Increased tendency to bruise
Mouth sores
Altered pigmentation of the skin

The side effects of capecitabine are similar, as it is converted to 5-fluorouracil once inside the body.
Cytarabine may also cause anorexia, fever and rash.

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LUNG

Incidence
Age-standardised incidence, Australia, 2000:
o 62.1 per 100,000 males
o 27.4 per 100,000 females
Most common cause of cancer death in men, second (to breast cancer) in women.

Risk factors/aetiology
Smoking!!!
Radiation exposure
Asbestos
Air pollution
Occupational exposures

Pathology
Small cell
o Most malignant, usually central or hilar tumour.
o Small, oat-like cells with little cytoplasm, poorly organised.
o Strong correlation with smoking.
o Frequent mediastinal lymph node involvement.
Non-small cell includes:
o Adenocarcinoma
Most common
Frequently presents peripheral mass.
o Squamous cell carcinoma
Closest correlation with smoking
Generally arises in or near hilus.
Better prognosis.
o Large cell
Probably poorly differentiated squamous cells or adenocarcinomas.

Symptoms and signs
Symptoms related to primary tumour:
Cough
Dyspnoea
Haemoptysis
Post-obstructive pneumonia
Chest pain suggests involvement of parietal pleura, or extension beyond lung
Shoulder pain, brachial plexus injury, Horners superior lobe tumours

Symptoms related to spread:
Hoarseness (left-sided lesions recurrent laryngeal nerve injury)
SVC obstruction (right-sided lesions)
Hemidiaphragm elevation phrenic nerve paralysis
Less commonly, dysphagia (oesophageal impingement), pericarditis

Commonly present with symptoms of metastases (especially adenocarcinomas) most common sites are brain,
pleural cavity, bone, liver, adrenals, contralateral lung, skin.

Diagnosis
Imaging chest CT.
Sputum cytology were good at this in WA.
Bronchoscopy can visualise tumour, take washings/brushings for cytology.
Percutaneous FNA may show pneumothorax
o If tumour is clearly resectable, probably not indicated (wont change management).
Serum markers NSE is a marker for small-cell.

Staging
For staging, clinical assessment important to find signs of metastases.
Also imaging CT, MRI, bone scan, PET; LFTs for liver metastases.
Staging is by TNM:

T (tumour) stages
Tis: only in cells lining airways (carcinoma in situ)
T1: < 3cm, no spread to pleura or main branches of bronchi
T2: > 3cm, involves main bronchus or spread to visceral pleura
T3: spread to nearby structures (chest wall, pleura etc)
T4: spread to mediastinum or organs within or > 1 tumour in same lobe

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N (nodal) stages
N0: no spread to lymph nodes
N1: lung or hilar lymph nodes
N2: subcarinal or mediastinal lymph nodes
N3: subclavicular lymph nodes or LN on side opposite cancerous lung

M (metastases) stages
M0: no mets
M1: mets

Stage grouping for non-small cell lung cancer
Once the T, N and M categories have been assigned, this information is combined (stage grouping) to
assign an overall stage of 0, I, II, III or IV.

Overall Stage T Stage N Stage M Stage
Stage 0 Tis (In situ) N0 M0
Stage IA T1 N0 M0
Stage IB T2 N0 M0
Stage IIA T1 N1 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
Stage IIIB Any T N3 M0
T4 Any N M0
Stage IV Any T Any N M1

Treatment modalities
Non-small cell tumours:
Stage I and II = surgical resection
o Stage I = lobectomy, wedge or sleeve resection
o Stage II = pneumonectomy, lobectomy, wedge or sleeve
o May be adjuvant radio or chemo
o Increasing interest in chemo.
o Curative intent
Stage III positive nodes
o Usually not resectable
o Aim to treat curatively or palliatively depending on cancer and individual
o May use combination of chemotherapy and radiotherapy as primary treatment
o Surgery in a few cases.
Stage IV metastatic disease
o Palliative chemo presuming good performance status.
Chemo, radio and surgery may be needed for symptom palliation.

Small cell tumours:
Chemotherapy is mainstay high response rates.
Adjuvant radiotherapy.
Surgery in a few early-stage cases.

Prognosis
Non-small cell
Stage I 40-60% 5-year survival with resection
Stage II 22-55% with resection (better for squamous cell)
Stage III 7-17% depending on treatment
Stage IV 1-year survival of 10% with palliative chemo

Small cell
Average survival of early-stage disease with aggressive treatment 2 years.




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MESOTHELIOMA
Malignancy of the pleura related to asbestos exposure
May not be evident until 20-30 years later.
Presents with SOB, cough, chest pain, weight loss, night sweats, bone/muscle pain.
Pleural effusion common.
May be found on screening x-ray (of exposed individuals).
Diagnosis is by CXR, CT, CT-guided biopsy.
Virtually never cured; survival may be months, 1-2 years (rarely people will live for years).
Palliative treatment involves chemo and radio.










PARANEOPLASTIC SYNDROMES
Most common with small cell lung cancer
Release of inappropriate hormones symptoms
May be the first presentation of the cancer

Common Symptoms
ACTH steroid hormones Cushingoid
o Occurs in SCC of lung, pancreatic ca, neural tumours
ADH hyponatraemia
o Occurs in SCC of lung, intracranial neoplasms
PTH or PG E hypercalcaemia (may also be due to metastatic bone destruction)
Calcitonin hypocalcaemia
o Occurs in SCC of lung, breast ca, renal ca, ovarian ca, adult T-cell leukaemia/lymphoma
Gonadotrophins gynaecomastia
Serotonin carcinoid syndrome flushing, abdo pain, diarrhoea, may be cardiac anomalies
o Occurs in bronchial (carcinoid) adenoma, pancreatic ca, gastric ca
Acanthosis nigricans
o Occurs in gastric ca, lung ca, uterine ca



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BREAST

Incidence
115.3 per 100,000 females in Australia in 2000 (age-standardised).

Risk factors/aetiology
Age
Family history especially history of cancer in younger women
Genetics BRCA-1, BRCA-2, most women will develop breast cancer
Radiation exposure
Smoking
Hormonal factors increased oestrogen exposure including HRT, nulliparity, early menarche and late
menopause

Pathology
Involvement of oncogenes (c-erb-B2, c-ras, c-myc) and tumour suppressors (pRb, p53).
50% are in upper outer quadrant.

Classification:
Carcinoma in situ (15-30% of tumours):
o DCIS usually detected on mammography; pre-cancerous lesion in about 1/3.
o LCIS carcinoma in 25-30% over 20 years; may be either breast. Generally seen along with
DCIS or IDC.
Invasive carcinoma (70-85%):
o IDC 80%
o Invasive lobular carcinoma 10%
o Other types medullary, colloid, tubular/cribriform, papillary

Presentation
Symptomatic
Women generally present with a lump found on self-examination
Most are post-menopausal (if post-menopausal and a new lump BC is #1 diagnosis)
May be fixation, tethering, skin changes (peau dorange), nipple discharge, lymph node involvement.
Be suspicious if unilateral, single duct and blood-stained nipple discharge
Nipple changes (eczema, itchy, ulceration) Pagets disease of the nipple

On screening mammography
20% are DCIS early stage good prognosis
Most are not palpable
Screening is every 2 years
Screening has breast cancer mortality significantly
But cost per life saved is > $3 million

NEVER cancer
Breast pain always hormonal
Multiduct discharge mammary duct ectasia (greeny/grey, offensive odour, > 75% of ducts)

Diagnosis
Triple test for investigation of a breast lump:
1. Clinical examination
a. If mass found, then
2. Imaging
a. US is first-line for women under 35 if suspicious perform mammogram
b. Mammogram for women over 35.
3. Cytology
a. Fine needle aspirate (FNA) or Core biopsy
b. If imaging is suspicious, refer directly to surgeon for investigation (may want a core biopsy).
c. If imaging shows a simple cyst, and aspiration reveals straw-coloured fluid with no persistent
lump or refilling no need for further investigation.
d. Anything else, refer to surgeon.

Surgeon may wish to perform further imaging, or core biopsy.

Staging
Staging is at surgery, by TNM:
Stage I is T1, N0, M0
Stage II is T1-2, N0-1, M0 or T3, N0, M0
Stage III is T0-2, N2 or T3-4, any N or any N, T3
Stage IV is any T, any N, M1


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T (tumour) stages
TX: cannot be assessed.
T0: no evidence of primary tumor.
Tis: carcinoma in situ
T1: < 2 cm
T2: 2 to 5 cm
T3: < 5cm
T4: invading chest wall or skin (any size)

N (node) stages
NX: cannot be assessed (eg. removed previously)
N0: no spread to lymph nodes
N1: 1 to 3 axillary lymph nodes or some cancerous cells found on sentinel LN biopsy of internal
mammary lymph nodes
N2: 4 to 9 axillary lymph nodes or has enlarged mammary lymph nodes
N3: > 10 axillary nodes, or involves multiple groups of nodes (eg. axilla + mammary) or clavicle

M (metastasis) stages
MX: cannot be assessed
M0: no mets
M1: mets

Staging
Stage 0: Tis, N0, M0 = Ductal carcinoma in situ
o Earliest form of breast cancer
o Lobular CIS is sometimes classed as Stage 0 but is not a true BC
LCIS = abnormal cells grow within lobules (milk-producing glands) but do not
penetrate through the walls of these lobules
o Pagets disease of the nipple (without underlying tumour) is also Stage 0

Stage I: T1, N0, M0
o < 2cm, no nodes or mets

Stage II
- Stage IIA: T0, N1, M0 -or- T1, N1, M0 -or- T2, N0, M0
o < 2cm and minimal spread to nodes, but no mets
-or-
o 2 5cm but no spread to nodes or mets

- Stage IIB: T2, N1, M0 -or- T3, N0, M0
o 2 5cm, minimal spread to nodes, but no mets
-or-
o > 5cm but no spread to nodes or mets

Stage III
- Stage IIIA: T0-2, N2, M0 -or- T3, N1-2, M0
o < 5cm (or cant be found) and has moderate spread (4 - 9) to nodes, but no mets
o > 5cm and has moderate spread (1 9) to nodes or to internal mammary nodes but no mets

- Stage IIIB: T4, N0-2, M0
o Grown into chest wall and has none or some spread to nodes, but no mets

- Stage IIIC: T0-4, N3, M0
o Tumour of any size (or cant be found) and has spread to > 10 axillary lymph nodes or to
distant lymph nodes (clavicle)

Stage IV: T0-4, N0-3, M1
o Metastasis of any tumour size or lymph node involvement
o Usual sites = bone, liver, brain, lung

Prognosis
Negative prognostic factors:
Increasing size
Histological grade
Lymph node metastases
ER ve, PR ve
HER2 +ve this allows treatment with Herceptin, but still a less favourable outlook
Younger age at diagnosis


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Stage 5-year Relative Survival Rate
0 100%
I 100%
II
IIA 92%
IIB 81%
III
IIIA 67%
IIIB 54%
IV 20%

TREATMENT MODALITIES
Surgical
The surgical treatment of primary breast cancer has devolved into two basic procedures:
The two have the same survival when they include axillary dissection.

1. Complete local excision (CLE) with axillary dissection:
Aims for clear histological margins with a rim of normal breast tissue around the periphery of the
primary tumour on all sides (option for breast conserving surgery).
The incidence of local recurrence is 12 per cent per year in women who have this followed by
radiotherapy.
-OR-

2. Total mastectomy with axillary dissection:
Complete excision of the breast parenchyma with preservation of the underlying pectoral muscles.
In comparable tumours, the incidence of local recurrence following mastectomy is 35 per cent at 10
years, or less than 0.5 per cent per year.

Axilla:
Dissection and irradiation are used in managing the axilla.
Axillary LN status is the most powerful single variable in estimating prognosis.
Prognosis is related to the number of axillary nodes which contain metastases.

Morbidity with LN dissection
o Nerve injury: Long thoracic nerve to serratus anterior
Thoracodorsal nerve to lats cant climb/ swim
Intercostobrachial nerve skin on inside arm
o 5% lifetime risk of lymphoedema of arm developing

Sentinel LN biopsy
LN from breast tumours drains first to one node then others.
If first LN contains no mets, others wont.
Radioisotope injection and drainage to find where to dissect; or a dye injection into lymphatics.
Is being studied but is not currently considered an alternative to axillary node dissection and the
procedure should only be performed as part of a controlled study or as a prelude to dissection.

Risks of surgery for breast cancer
Post-operative wound infection
Haematoma
Deep venous thrombosis
Women who have other unrelated diseases may have increased risk associated with anaesthesia.

Post surgical complications from surgery for breast cancer
Impact of loss of the breast on body image, appearance and self-esteem;
Pain in the upper medial aspect of the arm and chest wall
Lymphoedema of the arm (following axillary dissection)
o Can occur at any stage, even years after treatment
Partial necrosis of a soft tissue reconstruction
A second primary tumour in retained breast tissue
Weakness of the abdominal wall (where tissue is in the rectus flap method of reconstruction)
Systemic adjuvant therapy
Aims to treat undetectable remaining cancer, to reduce the risk of clinically evident metastatic
disease and local recurrence. Ultimately, this should improve survival.


13
Hormonal Therapy
Tamoxifen: recommended for most women with oestrogen receptor +ve tumours; significantly
improves recurrence-free and overall survival in women of all age groups and reduces incidence of
contra lateral cancer.
In women aged under 50, ovarian ablation can offer similar benefits.

Chemotherapy
Chemotherapy in combination with tamoxifen yields an increase in disease-free survival compared
with tamoxifen alone. Chemotherapy is much more likely to cause fertility problems and may induce
premature menopause.

Other Non-Surgical Mx
Respecting dignity, privacy and confidentiality
Treating the woman as a whole person rather than as a host for a cancer
Acknowledging and accommodating if possible, a womans work and family responsibilities
A good diet, exercise, sleep and relaxation and stress management are important for everybody,
including women with breast cancer.
Appropriate counselling for women with breast cancer has been found to improve emotional wellbeing
and quality of life.

Alternative Therapies
Majority arent evidence based and may interfere with conventional treatment.
Doctors should encourage discussion of the use of alternative therapies openly.

Follow up: Goals include
The early detection of local recurrence
Screening for a new primary breast cancer
Detection of treatment-related toxicities
Provision of psychosocial support
Identification of family history

Treatment by staging
LCIS:
If appears in isolation, watchful waiting is best annual clinical examination and bilateral mammography.
No indication for mastectomy.

Stage 0 = DCIS:
Image-guided core biopsy is optimal for diagnosis
Surgery local excision with adequate clearance margins (usually doesnt need lymphatic clearance)
Radiotherapy after surgery in some cases

Stage II = Early IDC
Early IDC is T1-2, N0-1, M0; ie tumour up to 5 cm, no fixed nodes, no metastases
Surgery (options):
o Breast-conserving plus radiotherapy
o Total mastectomy with axillary clearance, no radiotherapy
Lymph node dissection for staging (extent is variable).
Discuss possibility of reconstruction.
Post-mastectomy radiotherapy if high-risk.
Ovarian ablation should be considered for pre-menopausal women.
Adjuvant chemotherapy for everyone.
Hormonal therapy according to tissue receptors (eg. Tamoxifem)
Immunotherapy if Her-2 positive disease (monocloncal antibody Herceptin)

Stage III = Locally advanced IDC
Combination of modalities chemo + radio + surgery + hormonal
o eg. Chemo to shrink tumour, followed by surgery then radiotherapy + hormonal therapy
Intent is still curative
Neoadjuvant chemotherapy may help reduce tumour size before surgery

Stage IV = Metastatic IDC
Chemo + hormonal + supportive as appropriate
Usually palliative intent
Surgery for fungating or painful lesions, pinning of bones
Hormone therapy - tamoxifen, aromatase inhibitor
Chemotherapy - pts whose tumours have progressed on hormone therapy
Immune therapy - monoclonal antibody (Herceptin)
Radiation therapy for painful bony mets, CNS involvement, bronchial mets
Role of zoledronic acid (bisphosphonate) to prevent bone events

14
SKIN

MALIGNANT MELANOMA

Incidence
Age-standardised incidence, Australia, 2000:
o 54 per 100,000 males
o 30 per 100,000 females

Risk factors/aetiology
Sun exposure!!!
Pale skin
Genetics dysplastic naevus syndrome

Pathology
Four types:
1. Superficial spreading
o More common
o Spreads superficially in epidermis
o Becomes invasive after months-years.

2. Lentigo maligna
o Occurs in elderly people
o Initial slow-growing irregularly pigmented nodule
o Progresses to melanoma after many years

3. Nodular
o Presents initially as dark nodule
o Vertically invasive growth poor prognosis

4. Acral
o On palms and soles, near nails.

Symptoms and signs
ABCDE criteria for examining moles:
Asymmetry
Border
Colour
Diameter
Elevation

Note: 5% will be amelanitic (especially nodular ones) these can be quite sinister

Diagnosis
Dermoscopy examination, then excision of lesion and pathology.
o Take a 2 mm clearance margin.
o May use punch biopsy of larger lesions (but harder to interpret pathology)
Lymph node evaluation
Sentinel node biopsy if tumour >1 mm thick.

Treatment modalities
Surgical
o Excision of lesion with appropriate margins.
If lymph nodes positive, lymph node dissection.
Adjuvant therapies interferon, combined chemotherapies.

Prognosis
Related to thickness of lesion:
o < 0.76 mm 100% 5-year survival
o 0.76 - 1.5 mm 80%
o > 1.5 mm - < 40%
This is presuming original lesion is completely excised.

Alternatively:
o Localised at time of presentation (stage I or II) 89-96% 5-year survival
o Regional spread (stage III) 60%
o Distant metastases (stage IV) 14%


15
BASAL CELL CARCINOMA

Incidence
Commonest skin cancer in Australia.
Increases with age
Male > female.

Risk factors/aetiology
Pale skin, red/blonde hair, blue/green eyes
Freckling, sunburn in childhood
Family history
Immunosuppression
Arsenic exposure

Pathology
Pearly papules or expanding plaques
Some will be pigmented.
Advanced lesions ulcerate with extensive local invasion rodent ulcer.

Symptoms and signs
80% on head and neck.
Early lesions commonly small, translucent or pearly with raised telangiectasias.
Classic rodent ulcer has rolled edge and ulcerated centre.
Other forms include nodular or cystic, superficial (may resemble eczema), morphoeic and pigmented.
o Morphoeic lesions are typically ill-defined and more aggressive; may present late.

Diagnosis
Inspection
Excision
Pathology

Treatment modalities
Surgical excision cryotherapy or curettage and cautery can be used, but doesnt samples for
pathology.
Radiotherapy can be used in the elderly when extensive surgery will not be tolerated.
Photodynamic therapy
Fluorouracil
Imiquimod

Prognosis
Very rarely metastasise, although local invasion can be extensive.
Potential for recurrence
Also higher risk of melanoma.



16
SQUAMOUS CELL CARCINOMA

Incidence
Second most common skin cancer in Australia.
Increases with age
Male > female.

Risk factors/aetiology
Age
Sunlight!!
Tar exposure
Chronic skin ulcers
Old burn scars
Osteomyelitis
Ionising radiation
Tobacco/betel nut chewing (oral mucosa)

Pathology
Well-demarcated, red, scaling plaques.
Invasive lesions are nodular, variably hyperkeratotic, prone to ulceration.
Mucosal involvement leukoplakia.
Microscopically:
o Full-thickness epidermal atypia.

Symptoms and signs
Often develops from a preceding solar keratosis.
Initial lesion is thickening of skin with scaling, hyperkeratosis.
Later, warty, keratotic crust with poorly defined edge.
Lesion eventually becomes nodular and ulcerates.

Diagnosis
Inspection, excision and pathology.
Regional lymph node biopsy if spread is suspected.

Treatment modalities
Surgical excision, with margin >5 mm.
Radiotherapy if unable to tolerate surgery.
Adjuvant radiotherapy.
Topical fluorouracil.

Prognosis
< 5% will have spread at initial diagnosis.
5-year survival > 95% with treatment.

17
COLORECTAL

Incidence
Age-standardised incidence, Australia, 2000:
o 80.2 per 100,000 males
o 53.8 per 100,000 females

Risk factors/aetiology
(1) Sporadic colorectal cancer (8894%)
Older age
Male sex
Cholecystectomy
Ureterocolic anastomosis
Hormonal factors: nulliparity, late age at first pregnancy, early menopause
Environmental factors: diet, sedentary lifestyle, obesity, DM, smoking, occupational hazards, alcohol
Personal history of colorectal polyps, colorectal cancer, small bowel, endometrial, breast or ovarian
cancer
Familial colorectal cancer (20%) (where criteria for hereditary cancer not fulfilled) one 1
st
-degree
relative increases risk 2-3x; >2 1
st
-degree relatives increases risk 4-25x. Further increased if family
members were <45 yo.

(2) Hereditary colorectal cancer (510%)
FAP
Hereditary non-polyposis colorectal cancer
Peutz-Jeghers

(3) Colorectal cancer in inflammatory bowel disease (12%)
Ulcerative colitis
Crohns disease

Pathology
Adenoma-carcinoma progression.
Involves tumour suppressor genes (p53, APC); oncogenes (K-ras, c-myc, c-neu, c-erb-2).
Can appear anywhere in the colon, caecum and rectum
o Descending colon is least common.
May present as polypoid, fungating masses or annular, encircling masses.
Microscopically:
o Columnar cells invading as glands or cell clusters into submucosa and muscularis
o Inflammation of fibrosis of mesenchyme.
o May be signet-ring features or squamous-cell differentiation.

Symptoms and signs
Weakness, iron deficiency anaemia, abdominal pain, blood in stools, change in bowel habit (including
tenesmus), weight loss.
Large bowel obstruction MUST EXCLUDE!
O/E, may be palpable mass, signs of anaemia, hepatomegaly if liver metastases, jaundice if severe.

Diagnosis
Colonoscopy is gold standard.
Imaging may be useful
o CT, MRI.
o CT to look for liver metastases.
Tumour markers
o CEA for prognosis, follow-up, monitoring therapy.

Staging
T (tumour) stages
Tx: inconclusive or incomplete information
Tis: mucosa only (first layer), early stage (carcinoma in situ)
T1: through muscularis mucosa and extends into submucosa
T2: through submucosa and extends into muscularis propria
T3: completely through wall into subserosa, but no nearby organs/tissues
T4: completely through wall and into nearby tissues/organs

N (node) stages
Nx: incomplete information
N0: no spread to lymph nodes
N1: 1 3 lymph nodes
N2: 4 or more lymph nodes

18
M (metastasis) stages
Mx: incomplete information
M0: no metastasis
M1: metastasis

Stage Grouping
Stage 0: Tis, N0, M0
o Earliest stage, has not grown beyond inner layer (mucosa)
o Carcinoma in situ or intramucosal carcinoma

Stage I: T1, N0, M0 -or- T2, N0, M0
o Through muscularis mucosa and into submucosa
-or-
o May have also grown into muscularis propria
o But no lymph nodes or metastasis

Stage II
- Stage IIA: T3, N0, M0
o Through into outer layers but no spread to lymph nodes or metasasis

- Stage IIB: T4, N0, M0
o Not yet through wall completely and into nearby tissues
o No spread to lymph nodes or metasasis

Stage III
- Stage IIIA: T1-2, N1, M0:
o Through into submucosa or maybe further into muscularis propria
o And has spread to 1-3 lymph nodes, but no metasasis

- Stage IIIB: T3-4, N1, M0
o Through into subserosa or nearby tissues/organs
o And has spread to 1-3 lymph nodes, but no metastasis

- Stage IIIC: Any T, N2, M0:
o Spread to 4 or more lymph nodes, but no metastasis (any size)

Stage IV: Any T, Any N, M1:
o Any metastasis (any size, any nodes)
o Common sites = liver, lung, peritoneum, ovary


AJCC/TNM Dukes
O
I A
IIA B
IIB B
IIIA C
IIIB C
IIIC C
IV

Treatment modalities
Surgery
o Curative
o Stage I, II, III = wide local excision with anastomosis
o Stage IV = resection of obstructed sections, resection of liver if liver metastases
Adjuvant
o Chemotherapy for Dukes C, or any lymphatic spread.
Adjuvant/neoadjuvant radiotherapy in some cases.
Stage IV involves chemo + radiotherapy with palliative intent


19
Treatment based on staging
Stage I: Surgery
Stage II: Surgery + Adjuvant chemotherapy (maybe role in Stage II is still debatable)
Stage III: Surgery + Adjuvant chemotherapy
Stage IV: Surgery (resection) + Chemotherapy (palliative) + Radiotherapy (palliative)

Prognosis
Dukes Staging
A confined to bowel wall, not reached muscularis mucosae 96% 5-year
B breached muscularis mucosae but no lymphatic spread 70%
C regional lymphatic spread 50%
D distant metastases 10%

TNM Staging:
Stage I T1-2, N0, M0 80 - 95% 5-year
Stage II T3-4, N0, M0 65 - 75%
Stage IIIA, IIIB T1-4, N1, M0 42 - 55%
Stage IIIC any T, N2, M0 25 - 27%
Stage IV any T, any N, M1 0 - 7%


20
PROSTATE

Incidence
125 per 100,000 males in Australia in 2000 (age-standardised).

Risk factors/aetiology
Age > 55
Family history
High-fat diet
Heavy metal exposure
Ethnicity African American high-risk; Asian low-risk
Sedentary lifestyle
Smoking
Hormonal high testosterone

Pathology
70% occur in the peripheral part of the prostate, especially posteriorly.
Primary lesions usually poorly demarcated, firm, gritty nodules.
Microscopically:
o Adenocarcinoma
o Ranging from well- to poorly-differentiated.
Histologically:
o Graded by Gleason score = 1-5 depending on level of differentiation
o 1 = cells resemble normal tissue
o 5 = sheets, cords or nests of poorly-differentiated cells with necrosis
o Given 2 scores for the two most common patterns seen
o Then added together to give a Gleason score from 2 to 10
Spreads most commonly to bone, and can cause sclerotic as well as lytic lesions.

Symptoms and signs
Most are diagnosed in asymptomatic patients by screening.
Symptoms are similar to BPH urinary symptoms (poor stream, frequency), haematuria, etc.
Metastatic disease may present with bone pain.
Digital rectal examination (DRE) will show an enlarged, irregularly hard prostate.
o May be signs of lymph node involvement, bony metastases.

Diagnosis
Take blood for PSA before doing DRE
Digital rectal examination
Trans-rectal US and biopsy several core biopsy specimens taken for histology.
Imaging for staging, and looking for bone metastases.

Staging
T (tumour) stages
T0: no tumour
T1: tumour present, but not detectable clinically or with imaging
o T1a: found incidentally, takes up < 5% of tissue resected (for other reasons)
o T1b: found incidentally, takes up > 5% of tissue resected
o T1c: found in needle biopsy performed due to PSA
T2: tumour can be felt on examination, but has not spread outside prostate
o T2a: takes up < 50% of one of the prostates two lobes
o T2b: takes up > 50% of one of the prostates two lobes, but not both
o T2c: palpable in both lobes
T3: tumour has spread completely through prostatic capsule
o T3a: spread through capsule on one or both sides
o T3b: spread into seminal vesicle/s
T4: invaded other nearby structures

N (node) stages
N0: no lymph nodes
N1: regional lymph nodes only

M (metastasis) stages
M0: no metastasis
M1: metastasis
o M1a: lymph nodes beyond the regional ones
o M1b: bone
o M1c: other sites


21
Histological grade = G (Gleason) score
In most cancers, the histologic grade is used separately from the TNM staging
However, in prostate cancer, it is used in conjunction with the TNM status
GX: cannot assess grade
G1: closely resembles normal tissue = Gleason 2 - 4
G2: somewhat resembles normal tissue = Gleason 5 - 6
G3-4: barely or not at all resemble normal tissue = Gleason 7 - 10

Stage Tumor Nodes Metastasis Grade
Stage I T1a N0 M0 G1
Stage II
T1a N0 M0 G24
T1b N0 M0 Any G
T1c N0 M0 Any G
T1 N0 M0 Any G
T2 N0 M0 Any G
Stage III T3 N0 M0 Any G
Stage IV
T4 N0 M0 Any G
Any T N1 M0 Any G
Any T Any N M1 Any G

Treatment modalities
The options are
Treatment for early prostate cancer is contentious, as more patients will die with than of.
Watchful waiting
o Reasonable for men with life expectancy <10 years.
Trans-urethral resection of prostate (TURP)
o Risks of long-term incontinence and impotence.
o PSA monitoring needs to continue after surgery levels >0.1 ng/mL (ie any detectable level)
suggest there is some prostate tissue left.
Radiotherapy
o May be used as curative therapy
o Can be similar outcomes to TURP.
Hormonal therapy
o LHRH agonists
o Anti-androgens including cyproterone acetate.
o Side effects = hot flushes, sexual dysfunction and eventually become refractory.
o Poor prognosis at this stage.
Some new interest in use of chemotherapy.

Based on staging
Stage I
o Careful observation
o Radical prostatectomy with radiotherapy- EBRT, interstitial implantation transperineal
Stage II
o Radical prostatectomy
o EBRT plus androgen suppression therapy
o Interstitial implantation of radioisotopes
o Watchful waiting
Stage III
o ERBT with hormonal therapy (orchidectomy, LHRH agonist
o Hormonal treatment
o Radical prostatectomy (highly selected patients)
o Watchful waiting
o Importance of symptomatic rx for urinary symptoms- ERBT, hormonal therapies
Stage IV
o Hormonal manipulations
o Curative ERBT for highly selected M0 patients (+ hormonal therapy)
o Palliative radiotherapy
o Palliative surgery eg. TURP
Prognosis
Overall 5-year survival ~90%.
Depends on Gleason score, PSA and spread.
Well-differentiated, less aggressive tumours make PSA.
Excellent prognosis for Gleason score of 2 4; Poor for 8 - 10

22
TESTICULAR

Incidence
6 per 100,000 males in Australia in 2000 (age-standardised).
Incidence is increasing by 15-20% every five years.
Teratoma = most common in 15-30 y/o
Seminoma = 30-50 y/o
Mixed = 45%

Risk factors/Aetiology
Family history
Cryptorchidism
Klinefelter
Testicular feminisation
? Exposure to exogenous oestrogens
No proven link to vasectomy or injury

Pathology
Precursor is intratubular germ cell neoplasia can be cured by radiotherapy; increased risk on other
side.
95% are germ cell tumours, including: (however all have different properties)
o Seminomas (most common)
o Teratoma
o Spermatocytic seminoma
o Embryonal carcinoma
o Yolk sac tumours (in children)
o Choriocarcinoma (++ malignant)
Non-germ cell tumours include:
o Tumours of the gonadal stroma
o Lymphomas

Symptoms and signs
Scrotal mass is most common presentation always investigate any firm mass
Usually painless, may have enlargement of testis, asymmetry, tenderness or discomfort
Sometimes present with signs of lymph node spread (eg. back pain if spread to para-aortic nodes) or
metastasis (eg. SOB and haemoptysis if pulmonary mets)

Diagnosis
Physical examination
Tumour markers = AFP, hCG, LDH
Ultrasound
CXR, abdo and pelvic CT for staging and follow-up

Treatment modalities
Surgery:
o Radical orchidectomy generally done urgently provides tissue diagnosis
o Prosthesis are available
o Also discuss fertility cryo-preservation of sperm may be offered
Adjuvant treatment:
o Seminomas = radiotherapy
o Non-seminomatous germ cell tumours = may be adjuvant chemotherapy
Chemotherapy then surgery for masses > 10cm, involvement of LNs above diaphragm or metastasis

Prognosis
Good prognosis for seminoma most will present with stage I (5-year survival 95%) or II (85-90%).
Chemotherapy is frequently curative for later stages.
Non-seminoma much more likely to present with metastases. Survival varies widely depending on
grade and stage.



23
FEMALE CANCERS

CERVICAL ENDOMETRIAL OVARIAN
INCIDENCE 8th most common cancer in Aust
women
> 1,000 new cases per yr in Aust
> 300 die per yr in Aust
Incidence is due to screening
120,000 pre-cancerous cervical
abnormalities detected each yr
Virtually unknown in women <20
yrs of age and is very rare <25
Most common invasive
gynaecological cancer in
Australia, ranking 6
th
in terms of
incident cancers in women
~1400 new cases each year
50-70 yrs of age (rare <40yrs)
1200 women in Australia
diagnosed each year
PRESENTATION


Sx include:
o None early stage and
most treatable
o Abnormal vaginal
bleeding (postcoital,
postmenopausal or
spotting
intermenstrually)
o Persistent vaginal
discharge no
distinguishing
characteristics
Sx if advanced disease:
o Loss of apetite
o Weight loss
o Fatigue
o Pelvic, back or leg pain
o Incontinence (urine +-
faecal)
Signs include:
o None (early stages)
o Lesion on cervix
- Ulcer with firm edges
- Exophytic (like cauliflower)
- Hard and craggy
- Friable (pieces flake off)
Sx include:
o Most common is
postmenopausal bleeding
o Discharge
o Pain
Signs:
o None
o Enlarged uterus
o Metastatic disease

Correlation between the duration
of postmenopausal bleeding with
increasing tumour stage and
reduced survival time.


70% of cases diagnosed at
advanced stage due to
asymptomatic or non specific Sx
Sx include:
o Abdominal bloating
o Poor appetite
o Fatigue
o Unexplained weight gain
o Dysparuenia
o Constipation
o Heartburn
o Back pain
o Urinary frequency
o Fatigue
o Abdominal/pelvic pain
Signs include:
o Mass
o Distension
o Ascites
o Pain
o Intestinal obstruction
o Cachexia (late sign)
o Nothing (early stages)
RISK FACTORS

Increasing age
Sexual activity
o Multiple partners
o Early age at first sex
Human Papilloma Virus (sexually
transmitted, therefore, risk
increases with no. of partners)
Smoking
Increasing age
Obesity
Type II Diabetes
HTN
Anovulation (esp with PCOS)
PCOS assoc with pre menopausal
endometrial cancer
Long term use of unopposed
oestrogen in HRT

Tamoxifen risk increased 2-3
times and increases with use

Assoc with hereditary non-
polyposis colon cancer (HNPCC)
syndrome
Increasing age (80% are >50yrs)
Genetic factors (5-10%)
o Most hereditary ovarian
cancer is associated with
mutations in the BRCA1
gene
o Family history in > 1 first
degree relative with Dx
Caucasian women in industria-
lized countries with a higher
standard of living
?Diet meat, full-cream milk
Ovulatory factors
o Anovulation
o Having few or no
children
o Early age at menarche
o 1
st
child after age 30yrs
o Menopause after age
50yrs

95% of all ovarian cancer occurs
in women without risk factors and
many women with risk factors do
not develop ovarian cancer
TYPES 1. Epithilial (90%)
2. Borderline - less
aggressive than other
types
3. Germ cell
4. Sex cord stromal

24
DIAGNOSIS



Biopsy punch (if big lesion) or
cone (if small)
Pap smear screening, always
confirmed by biopsy, arent
diagnostic
Endometrial biopsy by D&C
Occasionally PAP smear gives a
clue (rarely)
US (endometrial thickness >5cm,
cancer more likely)
Paracentesis (if ascites) and
cytology
Ca125 tumour marker raised in
85%
Imaging (usually US)
Final histology by biopsy
TREATMENT

Surgical:
- Radical hysterectomy and pelvic
lymph node dissection
- Involves removal of uterus,
uterine canal, paremetrium
(tissue surrounding uterus) and
vagina
- Dont need to remove ovaries
Surgical:
- Total abdominal hysterectomy
and bilateral salpingo-
oophorectomy (the lymphatics
pass through here, ALSO this
cancer is dependent on
hormones)
- Nodes (depends on staging)

Surgical (main form of Rx):
- Debulking of tumour to increase
response to chemo
- Primary cytoreduction includes
total abdominal hysterectomy;
bilateral salpingo-oophorectomy;
omentectomy; and resection of
metastatic lesions from the
peritoneum or from bowel.
Radiotherapy:
- Can be used for all stages.
- Usually reserved for stage 2B or
above, for frail or very obese pnts
- Women dont like it because it
changes consistency of vagina
- Combined with chemo in
advanced cases
Radiotherapy:
Adjuvant in high risk cases i.e.
involvement of nodes
Radiotherapy:
- Not used
Chemo:
- Only used in combination with
radiotherapy
Chemo:
- Not used at present


Chemo:
- ALL cases have chemo to treat
residual disease
- About 70% will achieve a
significant response to 1
st
line
chemo and >50% will have no
evidence of cancer at the
completion of their chemo
Hormonal:
- Not used
Hormonal:
- High dose Provera
(medroxyprogesterone)



PREVENTION Cervical cancer is one of the most
preventable and curable of all
cancers.

PAP smears:
All women who have ever had sex
Includes if no longer have sex
1
st
pap smear at 18-20yrs of age
or 1-2yrs after first sex
(whichever is the later)
3 out of 4 women who develop
cervical cancer have never had a
Pap smear or not had one within
the recommended 2 yr interval
Should continue throughout their
life until age 70
With regular Pap smears at 2yr
intervals, & appropriate Rx when
abN detected most cervical
cancer could be prevented
There is currently no effective
screening procedure for early
detection

No evidence to support routine
screening

Education about postmenopausal
bleeding being abnormal and
needs investigation

Currently no accepted methods
for population screening or early
detection.

Possible protective effect of pill,
pregnancy and breast feeding.

CA125 can detect ovarian cancer
but positive result may be caused
by other conditions
(endometriosis, ovarian cysts,
smoking and caffeine
consumption). It is not
recommended as a stand-alone
test for ovarian cancer.
PROGNOSIS


~300 deaths every year
With regular PAP smears and
early detection, it is CURABLE
260 deaths every year
Most cancers are detected early
and therefore, have good
prognosis

<50% 5 year survival (due to late
stage Dx)
If cancer is Dx at early stage, 80-
100% 5yr survival rate
800 women in Australia die of
ovarian cancer each year






25
UTERINE

Incidence
15.8 per 100,000 females in Australia in 2000 (age-standardised) for uterine cancer.

Risk factors/aetiology
Obesity
Diabetes
Hypertension
Infertility
Oestrogenic stimulation late menopause, tamoxifen, low parity, etc

Pathology
Endometrial carcinoma:
o About 80% are endometrioid adenocarcinoma with histology resembling endometrial glands;
hormone responsive.
o Subtypes include secretory type and villoglandular type.
o Most are well- to moderately-differentiated and arise on a background of endometrial
hyperplasia.
Other types include serous (poor prognosis), mucinoid, clear-cell, mixed, squamous cell, transitional
cell, and small cell.

Can consider as type I low-grade, due to long duration of unopposed oestrogen action, well-
differentiated and good prognosis; or type II high-grade, arising from hyperplasia, poorly
differentiated and poorer prognosis.

Symptoms and signs
Generally present with discharge, irregular bleeding, or post-menopausal bleeding.

Diagnosis
Transvaginal US
o Endometrial lining should be <4-5 mm.
Biopsy
o Using Pipelle di Cornier
D&C with hysteroscopy and biopsy for histology
CA-125
o Potential tumour marker

Treatment modalities
Total hysterectomy, usually with bilateral salpingo-oophorectomy.
o Also allows lymph node dissection, collection of peritoneal fluid and washings.
Usually adjuvant radiotherapy (possibly neoadjuvant)
Adjuvant chemotherapy for higher stages
o Controversial for stage I and II.
Hormonal treatment with progestogens
o Sometimes alternating with tamoxifen especially for metastatic disease.

Staging and Prognosis
Depends on staging
FIGO system (determined at surgery):
o Stage I confined to endometrium and myometrium 85% 5-year survival
o Stage II cervical involvement 75%
o Stage III local spread - 45%
o Stage IV bladder or bowel, or distant metastases 25%

Because it is symptomatic early, most women will present in stage I or stage II.

Uterine sarcomas
Rare tumours, may be leiomyosarcoma, endometrial stromal tumour or mixed Mllerian tumour.
Generally present with bleeding.
Treated by hysterectomy; may be adjuvant radio or chemotherapy.
Poor prognosis.

26
OVARIAN

Incidence
12.0 per 100,000 females in Australia in 2000 (age-standardised).

Risk factors/aetiology
Age
Family history BRCA-1, BRCA-2
Nulliparity
Unopposed oestrogen exposure (OCP, pregnancy, lactation are protective).

Pathology
Most are epithelial in origin; may also be stromal or germ cell tumours.

Subtypes include:
o Serous (most common)
Cystic, with columnar lining, fluid-filled
~25% are malignant and a further 15% have malignant potential
o Mucinous
80% are benign
o Endometrioid
o Brenner tumours

Germ cell tumours are more likely to be malignant (especially teratomas).

Symptoms and signs
Generally asymptomatic early on. Symptoms are non-specific when they do occur abdominal fullness,
dyspepsia, poor appetite, bloating, vague pain. Occasionally, patients will present early with ovarian
torsion.

On examination, palpable ovarian mass; may also be umbilical mass (Sister Mary Joseph node);
ascites; paraneoplastic hypercalcaemia; symptoms of spread to pleura.

Diagnosis
Cancer marker CA-125
o Raised in 80%
o Not diagnostic but useful for monitoring therapy.
Trans-vaginal ultrasound
o Look for complex ovarian cyst with both cystic and solid components
o Sometimes with septations and internal echoes.
o Simple cysts are less sinister and should be watched.
Avoid percutaneous biopsy of complex cysts
o Can cause spread into peritoneum.

Staging (based on surgery)
Stage I tumour limited to ovaries
Stage II pelvic extension
Stage III upper abdomen or lymph node involvement
Stage IV distant spread

Treatment modalities
Surgery generally bilateral salpingo-oophorectomy.
o Can allow examination of peritoneal surfaces, omentectomy, biopsy of para-aortic lymph
nodes when appropriate, random biopsies of clinically uninvolved areas, and peritoneal
washings.
o Para-aortic node biopsy is essential where disease appears limited to look for spread.
Adjuvant chemotherapy almost always required
o Exception is a very few unilateral stage I tumours with low-grade histology.
Hormonal therapy both tamoxifen and progestogens.
Relapse is common, even after cure. Relapses may be chemotherapy-resistant.

Prognosis
Prognosis is poor because detection is often late.
Overall, ~ 50% 5-year survival.


27
CERVICAL

Incidence
Frank cervical carcinoma is uncommon now due to screening and treatment of CIN.

Risk factors/aetiology
HPV!!

Pathology
90% are squamous cell. Grossly, may be exophytic/fungating; ulcerating or infiltrative.

Symptoms and signs
May be asymptomatic. Otherwise slight bleeding/spotting; some bleeding after intercourse.

Diagnosis
Pap smear, colposcopy and biopsy.

Treatment modalities
LLETZ
Cone biopsy
For more advanced invasive carcinoma, total hysterectomy may be indicated (may also take tubes,
ovaries).
Radiotherapy for advanced carcinoma.

Staging and Prognosis
Stage 0 carcinoma in situ (=CIN III) 100% 5-year survival
Stage I carcinoma confined to the cervix 80 - 90%
Stage II beyond cervix but not into pelvic wall or lower 1/3 of vagina 75%
Stage III extending to pelvic wall or lower 1/3 of vagina 35%
Stage IV extends beyond pelvis 10 - 15%

28
HEAD AND NECK

Incidence
Risk factors/aetiology
Pathology
Symptoms and signs
Diagnosis
Treatment modalities
Prognosis



LYMPHOMA

Incidence
NHL age-standardised incidence, Australia, 2000:
21.5 per 100,000 males
15.6 per 100,000 females

Risk factors/aetiology
Pathology
Symptoms and signs
Diagnosis
Treatment modalities
Prognosis




29
LEUKAEMIA, MYELOMA, MYELODYSPLASTIC SYNDROMES

Incidence and Pathology
Acute Lymphoblastic Leukaemia(ALL)
o Childhood.
o Common ALL- presence of CD10.
o preB cell proliferation commonly affects 2-4 yr olds.
o T cell ALL- adolescent males.
Acute Myelogenous Leukaemia(AML)
o Older adults.
o AML; called also acute myeloblastic leukemia, acute myelocytic leukemia, acute myeloid
leukaemia.
o Neoplastic proliferation of blast cells derived from marrow myeloid elements.
Chronic Myeloid Leukaemia(CML)
o 20% of leukaemias, adults, 40-60yrs.
o Uncontrolled proliferation of myeloid cells.
Chronic Lymphocytic Leukaemia(CLL)
o Adults.
o Uncontrolled proliferation and accumulation of mature B lymphocytes.

Divided on basis of speed of evolution, cell type involved from light microscopy, expression of
cytosolic enzymes and surface antigens.

Risk factors/aetiology
Most leukaemia is initiated by specific gene deletions, mutations and translocations.
Eg- Philadelphia chromosome(reciprocal translocation between long arm of 22 and 9) assoc with 97%
of CML, ALL
Secondary AML- long term complication of chemo, radio or another myeloprolif disorder.


Symptoms and signs
Acute Leuk
o Bone marrow failure so:
Anaemia(tired, SOB), Fever, infection, abscess, bruising, bleeding (oral mucosa,
retina, lower limbs), enlarged LN, liver and spleen.
CML
o Chronic phase of 3-4 yrs followed by accelerated phase of fever, weight loss, splenomegaly,
anaemia, thrombocytopaenia, leucocytosis and increasing numbers of blast cells.
o Blastic phase of CML is characterised by development of acute leukaemia which is myeloid
(80%) or lymphoid in origin.
o Duration of the accelerated phase is variable blastic transformation occurs in a few months.
o Less frequently CML converts to myelofibrosis.
Symptoms insidious in onset anaemia, night sweats, fever, weight loss, abdominal
discomfort from splenomegaly.
o Leucostasis will lead to blurred vision, headaches, priapism and retinal haemorrhage.
CLL
o Disease can usually be kept under control for 9-10 years.
o Recurrent infections from neutropaenia and reduced Ig
o Symptoms of anaemia in the context of haemolysis
o Painless LN enlargement and splenomegaly.

Investigations and Diagnosis
Acute Leuk
o Peripheral blood film
o FBC low Hb, low platelets
o BM aspirate
o BM biopsy
o Also - cytogenetic analysis and immunophenotyping of leukaemic blast cells to confirm,
subclassify, prognosis.
AML
o Auer rods in cytoplasm, myeloperoxidase present
o Myeloid antigens (CD13, CD33) expressed.
ALL
o Greater than 30% lymphoblasts in the bone marrow
o Confirmed and classed according to expression of lymphoid antigens.
o Mostly derived from B cells and express CD10.
CML
o FBC low Hb, raised WCC, lots of myeloid precursors, platelets variable
o BM aspirate
o Oncogenes

30
CLL
o FBC low Hb, raised WCC, platelets low or normal
o Ig = low or normal
o Coombs test positive if haemolysis
o Peripheral blood smear
o Immunophenotyping CD5 and CD19

Treatment modalities
Treat the complications:
o Anaemia and thrombocytopaenia: blood + platelets transfusion
o Infection: prophylactic IV antibiotics
o Hyperuricaemia: allopurinol
o Tumour lysis syndrome ( Ca, PO4, K): monitor

AML
o Curable in 30% of patients under 60
o Chemotherapy to induce remission
o Further cycles of chemo or myeloablative therapy to maintain remission
o Bone marrow transplant
ALL
o Chemotherapy in cyclical combination
o Frequently involves CNS also use radiotherapy for meninges
o Maintenance chemotherapy required
CML
o -IFN induce remission in majority
o Given by scubut injection
o Also myeloablative therapy with bone marrow transplant
CLL
o Steroids
o Chemotherapy

Prognosis
AML
o Rapidly progressive - death in 2 months if untreated
o 3 yr survival with chemo = 20%.
o 70 - 80% under 60 go into remission
o Disease recurs in 60%.
ALL
o 90% of children respond to treatment, 70% are cured.
o 30% cure in adults.
o Worse prognosis if adult, male or Philadelphia translocation