Oncology 2 Flashcards
Oncology and Cancer in PASSMED High Yield Textbook, Oncology in Geeky Medics, Oncological Emergencies
Prostate cancer is now the most common cancer in adult males in the UK and is the second most common cause of death due to cancer in men after lung cancer.
What are the risk factors for developing it?
Increasing age
Obesity, tall stature
Anabolic steroids
Afro-Caribbean ethnicity
family history
How may prostate cancer present?
bladder outlet obstruction: hesitancy, urinary retention
haematuria, haematospermia
pain: back, perineal or testicular
digital rectal examination: asymmetrical, hard, nodular enlargement with loss of median sulcus
How may a cancerous prostate present on DRE?
may feel firm or hard, asymmetrical, craggy or irregular, with loss of the central sulcus. There may be a hard nodule.
The majority of prostate cancers (>95%) are adenocarcinomas. Where do they arise?
75% arise from the peripheral zone
20% in the transitional zone
5% in the central zone
Prostate adenocarcinomas can be categorised into two types:
Acinar adenocarcinoma – most common form of prostate cancer
Ductal adenocarcinoma – originates in the cells that line the ducts of the prostate gland
- grow and metastasise faster than acinar
All men over the age of 50yrs (40yrs in black African or Caribbean men) presenting with LUTS for the first time should receive what?
Counselling for a PSA test
The epithelial cells of the prostate produce prostate-specific antigen (PSA) .
What is this?
a glycoprotein that is secreted in the semen, with a small amount entering the blood
specific to the prostate, a raised level can indicate prostate cancer
What conditions should be met before performing a PSA test?
testing should not be done within at least:
6 weeks of a prostate biopsy
4 weeks following a proven UTI
1 week of DRE
48 hours of vigorous exercise / ejaculation
What can cause a raised PSA?
Prostate cancer
Benign prostatic hyperplasia
Prostatitis
Urinary tract infections
Vigorous exercise (notably cycling)
Recent ejaculation or prostate stimulation
The traditional investigation for suspected prostate cancer was a transrectal ultrasound-guided (TRUS) biopsy.
What are the potential complications with this procedure?
sepsis: 1% of cases
pain: lasting > 2 weeks in 15% and severe in 7%
fever: 5%
haematuria and rectal bleeding
In men thought to be at risk of prostate cancer, such as with a raised PSA or abnormal DRE, what investigation is indicated?
multi-parametric MRI scan of the prostate (mp-MRI)
Abnormal areas can be biopsied :
Transperineal biopsy
TransRectal UltraSound-guided (TRUS) biopsy
How can mp-MRI of the prostate be interpreted?
The results are reported on a Likert scale, scored as:
1 – very low suspicion
2 – low suspicion
3 – equivocal
4 – probable cancer
5 – definite cancer
Give some risks associated with prostate biopsy
Pain (particularly lower abdominal, rectal or perineal pain)
Bleeding (blood in the stools, urine or semen)
Infection
Urinary retention due to short term swelling of the prostate
Erectile dysfunction (rare)
What is the scoring system by which prostate cancers are graded?
The Gleason grading system - based on histiological appearance
higher score = worse prognosis
6 is considered low risk
7 is intermediate risk (3 + 4 is lower risk than 4 + 3)
8 or above is deemed to be high risk
Basic outline of mainstay of management for prostate cancer?
Radical prostatectomy, external-beam radiotherapy, and brachytherapy are the mainstay treatments of localised or locally advanced prostate cancer
Anti-androgen therapy is effective in metastatic disease
What is tumour flare?
What management step can reduce risk of this?
goserelin (GnRH agonist) management of prostate cancer = initial increase in testosterone levels before subsequent suppression of testosterone
bone pain, bladder obstruction and other symptoms
Prescribe cyproterone acetate- prevent paradoxical increase in symptoms with GnRH agonists
What is the main complication of external beam radiotherapy for mx of prostate cancer? How can it be managed?
proctitis (inflammation in the rectum) caused by radiation affecting the rectum
proctitis can cause pain, altered bowel habit, rectal bleeding and discharge
prednisolone suppositories can help reduce inflammation
What is brachytherapy? What are the potential side effects?
implanting radioactive metal “seeds” into the prostate- delivers continuous, targeted radiotherapy to the prostate
cystitis, proctitis, erectile dysfunction, incontinence and increased risk of bladder or rectal cancer.
Hormone therapy in prostate cancer aims to reduce the level of androgens (e.g., testosterone) that stimulate the cancer to grow. What options are available?
Androgen-receptor blockers such as bicalutamide
GnRH agonists such as goserelin (Zoladex) or leuprorelin (Prostap)
Bilateral orchidectomy to remove the testicles (rarely used)
What are the side effects of hormonal therapy for prostate cancer mx?
Hot flushes
Sexual dysfunction
Gynaecomastia
Fatigue
Osteoporosis
What are the possible complications of radical prostatectomy?
erectile dysfunction and urinary incontinence
What is the most common malignancy in men aged 20-30 years?
testicular cancer
Around 95% of cases of testicular cancer are germ-cell tumours. Germ cell tumours may essentially be divided into:
seminomas
non-seminomas: including embryonal, yolk sac, teratoma and choriocarcinoma
The peak incidence for teratomas is 25 years and seminomas is 35 years. Risk factors include:
family history
infertility (increases risk by a factor of 3)
cryptorchidism
Klinefelter’s syndrome
mumps orchitis
How may testicular cancer present?
a painless lump is the most common presenting symptom
pain may also be present in a minority of men
hydrocele
gynaecomastia
What causes gynaecomastia in men with testicular cancer?
this occurs due to an increased oestrogen:androgen ratio
germ-cell tumours → hCG → Leydig cell dysfunction → increases in both oestradiol and testosterone production, but rise in oestradiol is relatively greater than testosterone
leydig cell tumours → directly secrete more oestradiol and convert additional androgen precursors to oestrogens
What tumour markers may be present in men with testicular cancer?
seminomas: hCG may be elevated
non-seminomas: AFP and/or beta-hCG are elevated in 80-85%
LDH is elevated in around 40% of germ cell tumours
How can testicular cancer be diagnosed and managed?
dx: USS first line
Mx:
orchidectomy
chemotherapy and radiotherapy may be given depending on staging and tumour type
What is the prognosis for testicular cancer?
Prognosis is generally excellent
5 year survival for seminomas is around 95% if Stage I
5 year survival for teratomas is around 85% if Stage I
What is the most common tumour found in the pancreas?
Over 80% of pancreatic tumours are adenocarcinomas which typically occur at the head of the pancreas
Give some key associations of pancreatic cancer
increasing age
smoking
diabetes
chronic pancreatitis (alcohol does not appear to be an independent risk factor though)
hereditary non-polyposis colorectal carcinoma
multiple endocrine neoplasia
BRCA2 gene
KRAS gene mutation
How might pancreatic cancer present?
classically painless jaundice
- pale stools, dark urine, and pruritus
- cholestatic liver function tests (raised ALP, others normal)
abdominal mass
many patients present in a non-specific way with anorexia, weight loss, epigastric pain
loss of exocrine function (e.g. steatorrhoea)
loss of endocrine function (e.g. diabetes mellitus)
atypical back pain is often seen
migratory thrombophlebitis (Trousseau syndrome) is more common than with other cancers
Painless obstructive jaundice with lethargy and weight loss =
think pancreatic cancer
What abdominal masses may be seen in pancreatic cancer?
(in decreasing order of frequency)
hepatomegaly: due to metastases
gallbladder: Courvoisier’s law states that in the presence of painless obstructive jaundice, a palpable gallbladder is unlikely to be due to gallstones
epigastric mass: from the primary tumour
How can pancreatic cancer be investigated?
ultrasound
high-resolution CT scanning is the investigation of choice if the diagnosis is suspected
imaging may demonstrate the ‘double duct’ sign - the presence of simultaneous dilatation of the common bile and pancreatic ducts
How can pancreatic cancer be managed?
less than 20% are suitable for surgery at diagnosis
a Whipple’s resection (pancreaticoduodenectomy) is performed for resectable lesions in the head of pancreas. Side-effects include dumping syndrome and peptic ulcer disease
adjuvant chemotherapy is usually given following surgery
ERCP with stenting is often used for palliation
What is included under the umbrella term of head and neck cancer?
Oral cavity cancers
Cancers of the pharynx (including the oropharynx, hypopharynx and nasopharynx)
Cancers of the larynx
How may head and neck cancer present?
neck lump
hoarseness
persistent sore throat
persistent mouth ulcer
What is the most common cause of oesophageal cancer in the UK?
Where is it found?
Risk factors?
adenocarcinoma
Lower third - near the gastroesophageal junction
Risk factors:
GORD
Barrett’s oesophagus
smoking
obesity
What is the most common cause of oesophageal cancer in the developing world ?
Where is it found?
Risk factors?
squamous cell cancer
Upper two-thirds of the oesophagus
Risk factors:
smoking
alcohol
achalasia
Plummer-Vinson syndrome
diets rich in nitrosamines
What features may oesophageal cancer present with?
dysphagia: the most common presenting symptom
anorexia and weight loss
vomiting
other possible features include: odynophagia, hoarseness, melaena, cough
How can oesophageal cancer be diagnosed?
Upper GI endoscopy with biopsy is used for diagnosis
Endoscopic ultrasound is the preferred method for locoregional staging
CT scanning of the chest, abdomen and pelvis is used for initial staging
FDG-PET CT may be used for detecting occult metastases
Laparoscopy is sometimes performed to detect occult peritoneal disease
How can oesophageal cancer be managed?
Operable disease (T1N0M0) is best managed by surgical resection - the most common procedure is an Ivor-Lewis type oesophagectomy
Adjuvant chemotherapy
What is the biggest challenge of surgery for oesophageal cancer?
anastomotic leak with an intrathoracic anastomosis resulting in mediastinitis
Progressive dysphagia - first solids then liquids =
think oesophageal cancer!
Gastric cancer is a cancer of older people (half of patients are > 75 years) are has a male predominance (2:1).
What are the main risk factors for developing it?
Helicobacer pylori: triggers inflammation of the mucosa → atrophy and intestinal metaplasia
atrophic gastritis
diet: salt and salt-preserved foods, nitrates
smoking
blood group A
How does gastric cancer present?
abdominal pain : typically vague, epigastric pain or dyspepsia
weight loss and anorexia
nausea and vomiting
dysphagia: particularly if the cancer arises in the proximal stomach
overt upper gastrointestinal bleeding is seen only in a minority of patients
Which lymph nodes may gastric cancer metastasise to?
left supraclavicular lymph node (Virchow’s node)
periumbilical nodule (Sister Mary Joseph’s node)
How may gastric cancer be investigated?
diagnosis: oesophago-gastro-duodenoscopy with biopsy
- signet ring cells may be seen in gastric cancer
-higher numbers of signet ring cells are associated with a worse prognosis
staging: CT
How may gastric cancer be managed?
surgical options depend on the extent and side but include:
endoscopic mucosal resection
partial gastrectomy
total gastrectomy
chemotherapy
What are the most common bladder malignancies?
Urothelial (transitional cell) carcinoma (>90% of cases)
Squamous cell carcinoma ( 1-7% -except in regions affected by schistosomiasis)
Adenocarcinoma (2%)
Risk factors for urothelial (transitional cell) carcinoma of the bladder include:
Smoking
Exposure to aniline dyes (for example working in the printing and textile industry, examples are 2-naphthylamine and benzidine)
Rubber manufacture
Cyclophosphamide
Risk factors for squamous cell carcinoma of the bladder include:
Schistosomiasis
Smoking
How does bladder cancer most commonly present?
painless haematuria
How can bladder cancer be diagnosed?
Cystoscopy (a camera through the urethra into the bladder) can be used to visualise bladder cancers. The cystoscope can be rigid or flexible. Cystoscopy can be performed under local or general anaesthetic.
How can bladder cancer be managed?
Transurethral resection of bladder tumour (TURBT) may be used for non-muscle-invasive bladder cancer.
Intravesical chemotherapy (chemotherapy given into the bladder through a catheter) is often used after a TURBT procedure to reduce the risk of recurrence
BCG may be used as a form of immunotherapy. Giving the BCG vaccine into the bladder is thought to stimulate the immune system, which in turn attacks the bladder tumours.
Radical cystectomy
What is renal cell cancer associated with?
more common in middle-aged men
smoking
von Hippel-Lindau syndrome
tuberous sclerosis
autosomal dominant polycystic kidney disease
What features does renal cell cancer classically present with?
classical triad:
haematuria
loin pain
abdominal mass
pyrexia of unknown origin
What are the potential endocrine effects of RCC?
may secrete :
erythropoietin (polycythaemia)
parathyroid hormone-related protein (hypercalcaemia)
renin
ACTH
What is paraneoplastic hepatic dysfunction syndrome?
liver dysfunction - cholestasis and hepatosplenomegaly - caused by renal cell carcinoma
Left sided varicocoele may suggest the presence of what malignancy?
RCC
Due to compression of the renal vein between the abdominal aorta and the superior mesenteric artery (nutcracker angle)
How may renal cell carcinoma be managed?
for confined disease a partial or total nephrectomy depending on the tumour size
- patients with a T1 tumour (i.e. < 7cm in size) are typically offered a partial nephrectomy
alpha-interferon and interleukin-2 can reduce tumour size and also treat patients with metatases
receptor tyrosine kinase inhibitors (e.g. sorafenib, sunitinib)
Exposure to Aflatoxin (produced by Aspergillus) can cause which cancer to develop?
Liver - (hepatocellular carcinoma)
Exposure to Aniline dyes can cause which cancer to develop?
Bladder (transitional cell carcinoma)
Exposure to Asbestos can cause which cancer to develop?
Mesothelioma and bronchial carcinoma
Exposure to Nitrosamines can cause which cancer to develop?
Oesophageal and gastric cancer
Exposure to Vinyl Chloride can cause which cancer to develop?
Hepatic angiosarcoma
What are the most common tumours that metastasise to bone (in descending order)?
prostate
breast
lung
What are the most common sites of bone mets (in descending order)?
spine
pelvis
ribs
skull
long bones
Other than with bone pain, how may bone mets present?
pathological fractures
hypercalcaemia
raised ALP
Nausea and vomiting are common side-effects of chemotherapy. Risk factors for the development of symptoms include:
anxiety
age less than 50 years old
concurrent use of opioids
the type of chemotherapy used
How can risk of N+V due to chemotherapy be managed?
For patients at low-risk of symptoms then drugs such as metoclopramide may be used first-line. For high-risk patients then 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone
What is cyclophosphamide?
an alkylating agent used in the management of cancer and autoimmune conditions. It works by causing cross-linking of DNA
What are the ADRs of cyclophosphamide?
haemorrhagic cystitis: incidence reduced by the use of hydration and mesna
transitional cell carcinoma
myelosuppression
What is Mesna?
2-mercaptoethane sulfonate Na
a metabolite of cyclophosphamide called acrolein is toxic to urothelium
mesna binds to and inactivates acrolein helping to prevent haemorrhagic cystitis
What is Bleomycin? MOA? ADRs?
Cytotoxic antibiotic
Degrades preformed DNA
Lung fibrosis
What are Anthracyclines (e.g doxorubicin)? MOA? ADRs?
Cytotoxic antibiotics
Stabilizes DNA-topoisomerase II complex
Inhibits DNA & RNA synthesis
Cardiomyopathy
What is Methotrexate? MOA? ADRs?
Antimetabolite
Inhibits dihydrofolate reductase and thymidylate synthesis
Myelosuppression, mucositis, liver fibrosis, lung fibrosis
What is Fluorouracil (5-FU)? MOA? ADRs?
Antimetabolite
Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)
Myelosuppression, mucositis, dermatitis
What is 6-mercaptopurine? MOA? ADRs?
Antimetabolite
Purine analogue that is activated by HGPRTase, decreasing purine synthesis
Myelosuppression
What is Cytarabine? MOA? ADRs?
Antimetabolite
Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase
Myelosuppression, ataxia
How do Vincristine and Vinblastine work? ADRs?
Inhibits formation of microtubules
Vincristine: Peripheral neuropathy (reversible) , paralytic ileus
Vinblastine: myelosuppression
How does Docetaxel work? ADRs?
Prevents microtubule depolymerisation & disassembly, decreasing free tubulin
Neutropaenia
How does Irinotecan work? ADRs?
Inhibits topoisomerase I which prevents relaxation of supercoiled DNA
Myelosuppression
How does Cisplatin work? ADRs?
Causes cross-linking in DNA
Ototoxicity, peripheral neuropathy, hypomagnesaemia
How does Hydroxyurea (hydroxycarbamide) work? ADRs?
Inhibits ribonucleotide reductase, decreasing DNA synthesis
Myelosuppression
What is Li-Fraumeni Syndrome?
Autosomal dominant genetic condition
Consists of germline mutations to p53 tumour suppressor gene
High incidence of malignancies particularly sarcomas and leukaemias
What are BRCA 1 and 2 mutations?
Carried on chromosome 17 (BRCA 1) and Chromosome 13 (BRCA 2)
Linked to developing breast cancer
Associated risk of developing ovarian cancer
BRCA2 mutation is associated with prostate cancer in men
What is Lynch syndrome?
Autosomal dominant condition
Patients develop colonic cancer and endometrial cancer at young age
High risk individuals may be identified using the Amsterdam criteria
What is Gardeners syndrome?
Mutation of APC gene located on chromosome 5
Autosomal dominant familial colorectal polyposis
Patients have multiple colonic polyps
How should metastatic disease of unknown origin be investigated initially ?
FBC, U&E, LFT, calcium, urinalysis, LDH
Chest X-ray
CT of chest, abdomen and pelvis
AFP and hCG
What more specific investigations can be done for mets of unknown origin?
Myeloma screen (if lytic bone lesions)
Endoscopy (directed towards symptoms)
PSA (men)
CA 125 (women with peritoneal malignancy or ascites)
Testicular US (in men with germ cell tumours)
Mammography (in women with clinical or pathological features compatible with breast cancer)
How may spinal mets present?
Unrelenting lumbar back pain
Any thoracic or cervical back pain
Worse with sneezing, coughing or straining
Nocturnal
Associated with tenderness
How should suspected spinal mets be investigated?
neurological features = spinal cord compression must be suspected and acted on promptly
no neurological features = a whole spine MRI should be completed within one week. The whole spine should be imaged as patients commonly present with multi-level disease.
What is Positron Emission Tomography (PET)? Uses?
form of nuclear imaging which uses fluorodeoxyglucose (FDG) as the radiotracer. This allows a 3D image of metabolic activity to be generated using glucose uptake as a proxy marker.
Uses:
evaluating primary and possible metastatic disease
