Management of Individual Cancers Flashcards
Incidence of breast cancer?
Most common cancer in women – 19% of all new cases of female cancer. 1 in 12 women will develop breast cancer. Rare in men.
Screening for breast cancer?
Aged 50 and over – mammography.
Risk factors for breast cancer?
Increasing age
Increased periods of oestrogen exposure (late childbearing, nulliparity, early menarche, late menopause, obesity
Ionising radiation
Family history (first degree relative, premenopausal)
BRCA 1
Increased susceptibility to breast and ovarian cancer
BRCA 2
Early onset breast cancer and male breast cancer, but not ovarian.
Histology of breast cancer?
Ductal Carcinoma = Most common – 70-80% of all cases.
Lobular Carcinoma = 10% of cases – higher incidence of multicentric tumours within the same or opposite breast.
Others (rare) = Medullary, colloid, comedo, papillary
Presentation of breast cancer?
Most common presentation = breast mass.
Less common = nipple discharge, regional lymphadenopathy (axillary or supraclavicular), symptoms of metastatic disease
Investigations in breast cancer?
Bilateral mammography – detects multicentric tumours of synchronous primaries in opposite breast.
Fine needle aspiration cytology (FNAC), needle biopsy or excisional biopsy confirms diagnosis.
Bone scan/Liver imagining with USS or CT – those at high risk of disseminated disease
Staging of breast cancer? (T)
T0 – No primary tumour Tis – In situ disease, no invasive T1 – invasive tumour <2 cm T2 – Tumour 2-5 cm T3 – Tumour >5 cm T4 – Skin involvement
Staging of breast cancer? (N)
N0 – No lymph nodes
N1 – Mobile axillary lymph nodes
N2 – Fixed axillary lymph nodes
N3 – Internal mammary nodes
Staging of breast cancer? (M)
M0 – No metastases
M1 – Distant metastases
Staging of breast cancer? (TNM stages)
Stage 0 = Tis, N0, M0 Stage I = T1, N0, M0 Stage II = T2/3, N0, M0 or T0/1/2, N1, M0 Stage III = T or N > stage II, M0 Stage IV = Any T, Any N, M1
Management of breast cancer? (summary)
Surgery
Radiotherapy
Endocrine Therapy
Chemotherapy
Surgical management of breast cancer?
Mastectomy (radical or simple) or conservative (wide local excision) with post-operative radiotherapy.
Assessment of LN disease should be performed in patients with high risk disease (sentinel node biopsy) – reduces morbidity (lymphedema)
Radiotherapy treatment in breast cancer?
All patients need radiotherapy to residual breast tissue after surgery.
Local radiotherapy may be indicated if high risk of recurrence.
Axillary radiotherapy may be indicated if high risk –> risk of lymphedema.
Adjuvant endocrine therapy in breast cancer?
TAMOXIFEN
Reduces risk of recurrent by 25% - best in ER +ve tumours
Increased risk of VTE and endometrial cancer
AROMATASE INHIBITORS (ANASTRAZOLE)
Superior efficacy to tamoxifen in post-menopausal women with breast Ca
Fewer vascular and malignant events, but more problems with osteoporosis.
TRASTUZUMAB (HERCEPTIN)
Effective in metastatic and localised disease where the cancer over-expresses the target epithelial growth factor receptor (HER-2)
OVARIAN ABLATION
Reduces risk of recurrence in premenopausal women. May be performed by either oophorectomy or radiotherapy-induced menopause.
Endocrine therapy in metastatic breast cancer?
1/3 of patients respond – median duration of response to single therapy is 1-2 years. Chance of response higher in patients with ER-positive tumours (50-60%) compared with ER-negative tumours (5-10%).
OVARIAN ABLATION
Premenopausal – surgical, radiotherapy-induced or by GnRH analogues.
ANTI OESTROGENS
Tamoxifen daily until documented evidence of disease recurrence
AROMATASE INHIBITORS
Chemotherapy in breast cancer?
Adjuvant
Significantly reduces the risk of recurrence. Effect is greater in women less than 50 years.
Absolute benefit is lower the better the prognosis of the tumour.
Metastatic Disease
Aim = palliate symptoms and improve QoL. Combination chemo more effective although single agent treatment sometimes used in palliation.
Response rates = 45-80%, 5-13 months.
5 year survival in breast cancer?
Stage I – 84%
Stage II – 71%
Stage III – 48%
Stage IV – 18%
Incidence of colorectal cancer?
Second most common malignancy in UK – 10-15% of all malignancies. Colon cancer 1.5x more common than rectal cancer.
Screening for colorectal cancer?
Foecal occult blood testing – average risk populations – reduction in mortality between 15-18%.
Risk factors for colorectal cancer?
DIET
Diet rich in animal fats and meat and poor in fibre.
INFLAMMATORY DISEASE
UC – cumulative risk of 7-15% at 20 years of disease
Association with Crohn’s controversial
FAMILIAL
Hereditary non-polyposis colon cancer (HNPCC)
Familial adenomatous polyposis (FAP – APC gene 5q21-22)
Gardener’s syndrome
Histology of colorectal cancer?
40% occur in rectum, 20% in sigmoid colon, 6% in caecum, the rest in the remaining colon.
90-95% are adenocarcinomas
Epithelial - adenocarcinoma (mucinous or signet ring). Rare others = squamous cell carcinoma and adenosquamous carcinoma.
Carcinoid
Gastrointestinal stromal tumour
Primary malignant lymphoma
Clinical features of colorectal cancer?
Altered bowel habit, weight loss, rectal bleeding, vague abdominal pain – depends on site of primary tumour and degree of spread.
Occult tumours (right side of colon and caecum) can present with iron deficiency anaemia.
Investigation in colorectal cancer>
Rectal examination – 3/4 of all rectal lesions can be felt by digital examination
Scope – rigid sigmoidoscopy, flexible sigmoidoscopy, colonoscopy; allows visualisaiton and biopsy
Barium enema – less useful as no histology provided - gives apple core sign.
CT – staging and useful evaluation of bowel
CEA – marker can be used to monitor disease
Staging in colorectal cancer? (T)
TX – cannot be assessed
T0 – No evidence of primary tumour
Tis – Carcinoma in situ – intraepithelial or invasion of lamina propria
T1 – Invades muscularis propria
T3 - Invades through muscularis propria into subserosa or into non-peritonealised pericolic or perirectal tissues
T4 – Directly invades other organs/ structures/visceral peritoneum
Staging in colorectal cancer? (N)
NX – cannot be assessed
N0 – No LN involvement
N1 – 1-3 pericolic or perirectal LNs
N2 – 4+ pericolic or perirectal LNs
Dukes staging of colorectal cancer? (overall)
A = T1, N0, M0 or T2, N0, M0 B = T3, N0, M0 or T4, N0, M0 C = Any T, N1, M0 or Any T, N2/N3, M0 D = Any T, Any N, M1
Surgical management of colorectal cancer?
Radical resection = standard. Early stage can be cured by surgery alone.
Resection of liver mets in addition to primary may be beneficial.
Surgery or colonic stenting in palliative setting to prevent or manage obstruction lesion
Radiotherapy in colorectal cancer?
Used in rectal carcinomas – not used in bowel due to toxicity to adjacent organs.
Pre-operative or adjuvant radiotherapy indicated in high-risk carcinomas
Local recurrences can be palliated with radiotherapy
Metastatic bone disease may respond to palliative radiotherapy
Chemotherapy in colorectal cancer?
Accepted practice.
5-FU is most active agent. Oxaliplatin and Irinotecan are also used.
5 year survival in colorectal cancer?
A = 80% B = 50% C = 15-40% D = 5%
Incidence of lung cancer?
Second commonest cancer in the UK – 1 in 6 of all cancer cases. 1 in 11 men develop lung cancer.
Risk factors for lung cancer?
Age – increases after age 40
Smoking – 80/90% of cases
Occupation – asbestos exposure, uranium mining, ship building, petroleum roofing
Histology of lung cancer?
Arise from epithelium of large and medium sized bronchi – rarely from lung parenchyma itself.
Small Cell (18%) Non-Small Cell (82%)
SCLC?
18%
Arise from neuro-endocrine cells within lung.
Associated with neuropeptide secretion such as ADH (SIADH) or ACTH.
NSCLC?
82%
Squamous cell carcinoma (32% of NSCLC)
Adenocarcinoma (26% of NSCLC) – may arise from areas of lung damage, often peripheral and more common in women.
Large cell carcinoma (10% of NSCLC)
Non-small cell lung cancer not otherwise specified
Others = carcinoid, mesothelioma, sarcoma and lymphoma
Presentation of lung cancer?
Cough, dyspnoea, haemoptysis, chest pain or recurrent infection. Late presentation common.
SYNDROMES
Pancoast’s Syndrome – apical tumour which may invade brachial plexus producing Horner’s syndrome and pain in distribution of nerves
Recurrent laryngeal nerve palsy
SVC obstruction
Investigations in lung cancer?
CXR – 95% of tumours visible on plain CXR
Sputum cytology – 80% will have malignant cells detectable in sputum
Bronchoscopy – visualisation of bronchial tree; tumour biopsy and bronchial washings to be taken
Biopsy techniques – trans-thoracic biopsy under radiological biopsy.
Mediastinoscopy and biopsy of abnormal lymph nodes.
CT chest and upper abdomen – assesses extent of local and distant disease
PET scan – used in patients thought to have operable disease to check for mets not picked up on CT
Other diagnostic tests – head scans or isotope bone scans
Tumour markers – neuron specific enolase (NSE) and lactate dehydrogenase (LDH) – not routinely used
Chemotherapy in SCLC?
One of the most sensitive solid tumours. Chemotherapy = mainstay of treatment – responses within a few days.
Complications such as SVCO or cord compression can be treated with chemotherapy rather than radiotherapy.
Most patients will relapse (within 12 months of chemo) with chemo-resistant disease and die from rapidly progressive disease.
Radiotherapy in SCLC?
Highly radiosensitive tumour.
- Treatment of primary
- Prophylactic cranial irradiation (PCI) – brain mets common. But associated with memory impairment, functional deficit and dementia.
- Palliative
Surgery in SCLC?
Surgical intervention inappropriate in 90% of cases.
Surgery in NSCLC?
Possibility of cure if early stage. Mediastinal involvement is a contraindication to surgery.
3-5% mortality from pneumonectomy
Radiotherapy in NSCLC?
If not suitable for surgery –> radical radiotherapy.
Continuous hyperfractionated accelerated radiotherapy (CHART) – 3x per day for 12 consecutive days
Concurrent chemo-radiotherapy can improve outcomes
Palliative radiotherapy for SVCO
Chemotherapy in NSCLC?
Combination regimens can improve survival.
Palliative therapy offered to those well enough
May be given to shrink tumour before radical radiotherapy
Targeted therapies in NSCLC?
Tyrosine kinase inhibitors (erlontinib or gefitinib) – beneficial in NSCLC in palliative setting.
Prognosis of lung cancer?
SCLC – poor prognosis without treatment (2-4 months). With chemo, 11 months.
NSCLC – most die within 12 months of diagnosis.
Stage 1 = 50% Stage 2 = 40% Stage 3a = 25% Stage 3b = <5% Stage 4 = median survival 6 months
Incidence of testicular cancer?
2000 new cases each year. Predominantly 15-45 year old males.
Screening in testicular cancer?
No role at present for screening – self-examination programmes promoted.
Risk factors for testicular cancer?
Maldescent of testes, testicular atrophy and family history.
Histology of testicular cancer?
GERM CELL (95%) = seminoma (40%) or NSGCT (teratoma, yolk sac, combined seminoma/non-seminoma)
NON-GERM CELL (lymphoma or rare)
Spread of testicular cancer?
Early spread is common via lymphatics to para-aortic nodes (embryological origin from para-renal tissues). Blood borne spread to lungs, liver, bone and brain.
Presentation of testicular cancer?
Painless testicular swelling.
Metastatic spread can be indicated by cough or dyspnoea (lung mets) or as low back pain due to para-aortic involvement.
Investigations in testicular cancer?
TESTICULAR USS
Differentiates solid from fluid filled masses. Can also differentiate between teratomas and seminomas.
TUMOUR MARKERS
bHCG raised in seminomas and non-seminomas in 75% of patients.
AFP only raised in presence of non-seminomatous elements.
LDH is a useful marker to assess prognosis, response to treatment and detect relapse.
ORCHIDECTOMY
Trans-scrotal biopsy contra-indicated due to risk of dissemination of tumour
Orchidectomy required for tissue diagnosis and definitive therapy.
Biopsy of contralateral testicle indicated in patients with history of maldescent because there is an increased risk of bilateral disease.
IMAGING
CT scanning of chest, abdomen and pelvis – undertaken post-operatively.
Staging of testicular cancer?
Royal Marsden Staging System
I = confined to testicle II = involving para-aortic lymph nodes below the diaphragm III = involving para-aortic lymph nodes above the diaphragm IV = involving visceral metastases
Another grouping/staging system for germ cell tumours?
IGCCC prognostic grouping
Takes into account spread and tumour markers and gives GOOD, INTERMEDIATE or POOR prognosis.
5 year survival for germ cell tumours? (IGCCC)
NON-SEMINOMA
good = 92%
intermediate = 80%
poor = 48%
SEMINOMA
good = 86%
Intermediate = 72%
poor = doesn’t exist
management of germ cell tumours? (general)
GC tumours = highly malignant with rapid growth and high metastatic potential but are very sensitive to chemotherapy and radiotherapy.
Surgery in testicular cancer?
Orchidectomy via the inguinal canal. Biopsy of contralteral side often perofmed at time of operaiton.
Chemotherapy in testicular cancer?
Adjuvant chemotherapy used in higher risk stage I disease. Some opt for surveillance in low risk stage I disease.
3-4 cycles of BEP – number depends on type, extent and prognosis.
BEP is intense – expected rates of neuropenia and needs specialist management for belomycin and high-dose cisplatin toxicity.
Radiotherapy in testicular cancer?
RTx to para-aortic nodes is used in stage I/II seminomas as adjuvant treatment.
Used in conjunction with chemo in sites of bulky metastasis in teratoma.
Palliative radiotherapy to bone, brain and nodes.
Prognosis in testicular cancer?
Bulky tumour sites carry worse prognosis
.
Presence of pulmonary metastases does not affect prognosis.
Adverse histological markers = presence of yolk sac elements, vascular invasion or lymphatic invasion
Raised tumour markers are associated with poor prognosis
Incidence of prostate cancer?
Commonest new cancer diagnosis in men – 1 in 4 of every male cancer.
Second highest number of deaths in men with cancer.
Increases with age – majority over 70.
Risk factors for prostate cancer?
Age
Ethnicity – African/Afro-Caribbean background
FH of prostate cancer and men whose mother was diagnosed with breast cancer
Clinical presentation of prostate cancer?
May be asymptomatic and diagnosed by rectal exam or PSA test.
Lower urinary tract symptoms – poor stream, nocturia, dribbling and increased frequency; impotence common.
Some present with bone complications – anaemia, pain, pathological fracture or spinal cord compression
Examination
Enlarged, hard, craggy gland felt, with obliteration of median sulcus.
Histology of prostate cancer?
95% = adenocarcinomas in posterior or peripheral part of prostate gland.
Grade = Gleason grade
Investigation in prostate cancer?
Digital rectal exam and PSA blood test
MRI – can visualise prostatr well and delineate any extra-capsular spread
Isotope radionucleotide bone scan - can detect bone involvement
Transrectal biopsy – to confirm diagnosis – not required when clinical suspciison very high PSA >100 with +ve bone scan)
Staging of prostate cancer? (T)
T1 = clinically unapparent tumour not palpable or visible by imaging T2 = confined within prostate, not palpable T2a = <50% of one lobe T2b = >50% of one lobe T2c = both lobes T3 = extends through prostate capsule T4 = Fixed or invades adjacent structures other than seminal vesicles; bladder neck, external sphincter, rectum, levator muscles and/or pelvic wall
Staging of prostate cancer? (N)
N0 = No regional LN involvement N1 = Regional LN involvement
Staging of prostate cancer? (M)
M0 = No distant mets M1 = distant mets M1a = Nonregional LNs M1b = Bone(s) M1c = Other or multiple sites with or without bone disease
Management of prostate cancer? (general)
Observation Surgery Radiotherapy Hormonal Therapy Chemotherapy
Management of prostate cancer? (observation)
Low and intermediate risk local prostate cancer (PSA <20, Gleason 6 or7, up to T2b) – should be offered active surveillance.
Radical treatment unlikely to benefit men with life expectancy of <10 years.
Management of prostate cancer? (surgery)
Localised disease (T2 or less) can be treated by radical prostatectomy with curative intent. Can lead to temporary or lasting impotence and incontinence.
Palliative – trans-urethral resections can be used to relieve lower urinary tract symptoms
Management of prostate cancer? (RTx)
Low and intermediate risk cancer. Should be delayed until at least 6 weeks following trans-urethral resection to prevent stricture formation.
Management of prostate cancer? (Hormonal therapy)
LHRH AGONISTS (leuprorelin, goserelin) Reduces level of circulating testosterone. Side-effects = impotence, loss of libidio and tumour flare. Tumour flare avoided by concomitant anti-andorgen therapy. Long term consequences = increased cardiac risk and osteoporosis.
GnRH Antagonist (degarelix) • Castrate levels of testosterone without tumour flare. Indicated when tumour flare may lead to significant problems (MSCC)
OESTROGEN THERAPY
Oestrogens inhibit LHRH production from hypothalamus – rarely best option due to side-effects; impotence, loss of libido, gynaecomastia, MI, stroke, PE.
ANTI-ANDROGENS
(bicalutamide, enzalutamide)
Compete with androgens for sites on the androgen receptor.
BILATERAL ORCHIDECTOMY
Widely used in countries without access to medical therapy
Chemotherapy in prostate cancer?
Early use of docetaxel (in combination with prednisolone) and cabazitaxel – shown to improve QoL and survival in patietns with castrate-refractory metastatic disease.
Significant prolongation in survival – extra 15 months – recent change in practice.
Common primaries of liver mets?
Colon, lung, breast
Common primaries of lung mets?
Breast, lung, kidney
Common primaries of brain mets?
Lung, breast, melanoma
Common primaries of bone mets?
PB KTL
Prostate, breast, kidney, thyroid, lung
Common primaries of peritoneal mets?
Ovary, GI tract (esp. stomach), pancreas
Common primaries of high cervical node mets?
H+N, thyroid, lung
Common primaries of lower cervical/supraclavicular node mets?
H+N, lung, breast, GI tract
Common primaries of axillary node mets?
Breast, lung, melanoma
Common primaries of inguinal node mets?
Ovary, prostate, ano-rectal, vulva
Young men with disease in the midline
e.g. para-aortic nodes, medstinal nodes, neck nodes, brain mets – may well have a germ cell tumour. Tumour markers may be diagnostic – should see an oncologist within 24 hours.
Women with axillary or thoracic nodes
Breast cancer – empirical treatment often very effective for some years
Women with abdominal carcinomatosis
Ovarian cancer – empirical treatment often very effective for some years
Multiple moderate sized abnormal nodal sites
Lymphoma - empirical treatment often very effective for some years
