Oncology: Principles

• Basics: Cancer in the UK | Prevention and Screening | Suspected Cancer Referral | Diagnosis, Staging and Tumour Markers | Planning Treatment
• Treatments: Surgery and Radiotherapy | Chemotherapy | Chemotherapy Side Effects | Immunotherapy and Its Side Effects | Targeted Therapies | Hormone Therapies
• Special topics: Inherited Cancer Risk | Cancer of Unknown Primary | Cancer in Older People | Living With and Beyond Cancer
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🎗️ Oncology principles apply to every cancer: finding it early, staging it, deciding treatment intent in an MDT, and recognising and managing treatment side effects. Patients on cancer treatment often present first to GPs, emergency departments and medical teams - so every doctor needs to know the common toxicities. Specific cancers are covered in the organ chapters and the next two oncology chapters; oncological emergencies have their own chapter.
Your four questions for every patient: Could this be cancer - which pathway does the patient need? What is the stage, and is the intent curative or palliative? What treatment is the patient on, and could this problem be a side effect? What matters most to the patient, and are their wider needs being met?

Cancer in the UK

• About 1 in 2 people in the UK will develop cancer in their lifetime; there are around 400,000 new cases a year.
• Commonest cancers: Breast, prostate, lung and bowel - together over half of all cases.
• Biggest killers: Lung cancer, then bowel, prostate, breast and pancreas.
• Survival has doubled since the 1970s - about half of patients now survive 10 years or more, but it varies hugely by cancer type and stage.
• Stage at diagnosis matters most - early-stage cancers are far more curable. The NHS aims to diagnose 75% of cancers at stage 1 or 2.
• Inequalities: Outcomes are worse in deprived areas and in some ethnic groups, partly from later diagnosis.

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Prevention and Screening

About 4 in 10 cancers are preventable. The main risk factors:

• Smoking - the biggest single cause (lung, head and neck, bladder, pancreas, kidney, oesophagus, cervix and more).
• Excess weight - the second biggest (bowel, breast, endometrial, kidney, oesophageal, pancreas, liver).
• UV radiation - melanoma and skin cancers.
• Alcohol - mouth, throat, oesophagus, breast, liver, bowel.
• Infections - HPV (cervix, anus, oropharynx), hepatitis B and C (liver), H. pylori (stomach), EBV, HIV.
• Diet low in fibre and high in processed meat; inactivity.
• Occupational exposures (asbestos, radon).

Vaccines:

• HPV vaccine for all children at 12–13 (now a single dose), and for men who have sex with men up to 45.
• Hepatitis B vaccine in the childhood schedule.

NHS screening programmes (England):

💡 Clinical Pearl: Screening is for people without symptoms. Someone with symptoms needs a diagnostic referral, even if a recent screening test was normal.

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Suspected Cancer Referral

• NICE NG12 sets out symptoms that need an urgent suspected cancer referral or direct-access test. Patients should know why they are being referred.
• Faster Diagnosis Standard - cancer diagnosed or ruled out within 28 days of urgent referral.
• Key red flags (examples - see the organ chapters for details):
  • Dysphagia at any age - urgent OGD.
  • Rectal bleeding, change in bowel habit or iron deficiency - FIT, then referral if 10 µg/g or more.
  • Unexplained haemoptysis over 40; persistent cough, chest symptoms or weight loss in smokers over 40 - chest X-ray.
  • Breast lump over 30 - urgent referral.
  • Visible haematuria over 45 - urgent referral.
  • Raised PSA or abnormal prostate on examination - urgent referral.
  • Postmenopausal bleeding over 55.
  • Persistent bloating in women over 50 - CA125.
  • Jaundice over 40 - pancreatic cancer pathway.
  • Suspicious skin lesion (melanoma) - urgent referral.
  • Unexplained lymphadenopathy, bone pain, or new neurological deficits.
• Non-specific symptoms (weight loss, fatigue, vague abdominal pain, GP "gut feeling") - Rapid Diagnostic Centres.
• Safety-netting: Arrange review, explain what to watch for, and follow up results. Many cancers present after several consultations.
• Emergency presentation (about 1 in 5 cancers) carries worse survival.

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Diagnosis, Staging and Tumour Markers

• Tissue diagnosis - biopsy (core, excision, endoscopic, image-guided) or cytology:
  • Histology type and grade (how abnormal the cells look).
  • Immunohistochemistry (e.g. ER, PR, HER2 in breast cancer; PD-L1).
  • Molecular testing - EGFR, ALK, KRAS, BRAF, mismatch repair, BRCA - through the NHS Genomic Medicine Service. This increasingly decides treatment.
• Staging - how far the cancer has spread:
  • TNM - T (tumour size or depth), N (lymph nodes), M (metastases) - combined into stages I–IV.
  • Imaging: CT chest, abdomen and pelvis; MRI (rectum, brain, prostate, liver); PET-CT (lung, lymphoma, oesophagus, head and neck); bone scan; endoscopic ultrasound.
• Performance status (ECOG) - key for treatment decisions:
  • 0 - fully active.
  • 1 - restricted in strenuous activity, can do light work.
  • 2 - up and about over half the day, self-caring, can't work.
  • 3 - in bed or chair over half the day, limited self-care.
  • 4 - completely disabled, bedbound.
• Tumour markers - mostly for monitoring response and recurrence, not for screening:
  • PSA - prostate (also raised by infection, BPH, urinary retention, catheterisation).
  • CA125 - ovarian (also raised by endometriosis, fibroids, ascites from any cause, heart failure).
  • CEA - colorectal (also raised in smokers, IBD).
  • CA19-9 - pancreas and biliary (raised in biliary obstruction).
  • AFP - HCC and germ cell tumours.
  • hCG - germ cell tumours and gestational trophoblastic disease.
  • LDH - lymphoma, germ cell tumours, melanoma.
  • Calcitonin - medullary thyroid cancer.
  • Chromogranin A - neuroendocrine tumours.

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Planning Treatment

• Multidisciplinary team (MDT) - surgeons, oncologists, radiologists, pathologists, specialist nurses - reviews every new cancer and recommends options.
• Treatment intent:
  • Curative (radical) - aims to eradicate the cancer (surgery, radical radiotherapy or chemoradiotherapy).
  • Neoadjuvant - treatment before surgery to shrink the tumour (e.g. rectal, oesophageal, breast cancer).
  • Adjuvant - treatment after surgery to reduce the risk of recurrence.
  • Palliative (non-curative) - to control the cancer, extend life and relieve symptoms.
• Shared decisions - balance benefit, side effects, the patient's priorities, frailty and other illnesses. Not having anti-cancer treatment is a valid choice.
• Clinical nurse specialist - a named key worker for every patient.
• Holistic needs assessment - physical, emotional, practical, financial and spiritual needs.
• Clinical trials - offer where available.
• Prehabilitation - exercise, nutrition and psychological support before treatment improve outcomes.

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Surgery and Radiotherapy

Surgery - the main curative treatment for most solid tumours. Also used for:

• Diagnosis (biopsy).
• Staging (sentinel node biopsy).
• Reconstruction.
• Palliation (bypass, stents, fixation of fractures).
• Removal of isolated metastases (liver, lung).

Radiotherapy - ionising radiation damages cancer cell DNA:

• Types:
  • External beam - given in fractions over days to weeks.
  • Stereotactic (SABR) - high-precision, a few large doses (early lung cancer, brain and other metastases).
  • Brachytherapy - radioactive sources placed inside or next to the tumour (prostate, cervix).
  • Radioisotopes - radioiodine (thyroid), radium-223 (prostate bone metastases), lutetium-177 (NETs, prostate).
  • Proton beam - selected children's and skull base tumours.
  • Chemoradiotherapy - chemotherapy makes radiotherapy more effective (cervix, head and neck, anus, oesophagus, rectum, lung).
• Acute side effects (during treatment and for weeks after - depend on the area treated):
  • Fatigue.
  • Skin reactions (redness, peeling).
  • Mucositis (head and neck), oesophagitis (chest).
  • Diarrhoea and proctitis (pelvis); cystitis.
  • Nausea; hair loss in the treated area.
  • Radiation pneumonitis (1–6 months after chest radiotherapy - cough, breathlessness, fever; steroids).
• Late side effects (months to years):
  • Fibrosis; strictures; lymphoedema.
  • Infertility; early menopause.
  • Heart and vascular disease (chest).
  • Hypothyroidism (neck).
  • Dry mouth and dental decay (head and neck); osteoradionecrosis.
  • Bowel and bladder problems (pelvis).
  • Cognitive decline (brain).
  • Second cancers.
• Palliative radiotherapy:
  • Bone pain - often a single 8 Gy fraction relieves pain in most.
  • Spinal cord compression.
  • Bleeding (haemoptysis, haematuria, vaginal).
  • Brain metastases.
  • Obstruction (airway, SVC).

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Chemotherapy

How it works: Chemotherapy kills rapidly dividing cells, which is why it also affects the bone marrow, gut lining, hair follicles and gonads. It is given in cycles (e.g. every 2–3 weeks) to allow normal tissues to recover. Doses are based on body surface area (carboplatin on kidney function).

⚠️ Safety Pearl: Chemotherapy prescribing is a specialist task, with checked protocols. Never prescribe or continue oral anti-cancer drugs (e.g. capecitabine) without clear specialist guidance - dosing errors cause serious harm.

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Chemotherapy Side Effects

• Bone marrow suppression:
  • Neutrophils are lowest about 7–14 days after treatment (the "nadir").
  • Neutropenic sepsis - any patient on chemotherapy who is unwell or has a temperature of 38 °C or more needs IV antibiotics within 1 hour (see the Oncological Emergencies chapter). Patients should call the 24-hour acute oncology helpline.
  • Anaemia; thrombocytopenia.
  • G-CSF can prevent or shorten neutropenia.
• Nausea and vomiting:
  • Prevent according to how emetogenic the regimen is:
    • 5-HT3 antagonists (ondansetron).
    • Dexamethasone.
    • NK1 antagonists (aprepitant) for highly emetogenic drugs (cisplatin).
    • Olanzapine.
  • Metoclopramide for breakthrough symptoms.
  • Anticipatory nausea - lorazepam.
• Mucositis - mouth care, mouthwashes, pain relief; check for candida and herpes.
• Diarrhoea - loperamide; check for infection (C. difficile, neutropenic colitis); admit if severe or with fever. Immunotherapy colitis is different (see below).
• Hair loss - usually temporary; scalp cooling helps with some drugs.
• Fatigue - very common; exercise helps.
• Peripheral neuropathy - platinums, taxanes, vinca alkaloids, bortezomib; may need dose reduction; sometimes permanent.
• Fertility - offer sperm, egg or embryo storage before treatment. Chemotherapy is teratogenic - effective contraception during treatment.
• VTE - cancer and chemotherapy greatly increase risk.
• Extravasation - leakage of a vesicant drug (e.g. anthracyclines, vinca alkaloids) causes pain and tissue necrosis. Stop the infusion, aspirate, and follow the protocol (e.g. dexrazoxane for anthracyclines).
• Tumour lysis syndrome - see the Oncological Emergencies chapter.
• Organ toxicities - heart (anthracyclines, trastuzumab, 5-FU), lungs (bleomycin), kidneys (cisplatin), bladder (cyclophosphamide), hearing (cisplatin).
• "Chemo brain" - problems with memory and concentration.

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Immunotherapy and Its Side Effects

Immune checkpoint inhibitors release the "brakes" on T cells so they attack cancer. They have transformed melanoma, lung, kidney, bladder, head and neck and many other cancers.

• PD-1 inhibitors - pembrolizumab, nivolumab.
• PD-L1 inhibitors - atezolizumab, durvalumab.
• CTLA-4 inhibitors - ipilimumab (more toxic, especially combined with nivolumab).

Immune-related adverse events (irAEs) - the immune system can attack any organ, at any time (even months after stopping):

• General approach (graded by severity, CTCAE):
  • Grade 1 - continue with monitoring.
  • Grade 2 - hold treatment; oral steroids.
  • Grades 3–4 - stop; IV steroids; admit; specialist input.
• Taper steroids slowly (over at least 4–6 weeks); give PCP prophylaxis with prolonged high-dose steroids.
• Endocrine side effects are treated with hormone replacement - steroids are not needed for thyroid problems.
• Always ask whether a patient has had immunotherapy - and contact the acute oncology team.
• CAR-T cells and bispecific antibodies - cytokine release syndrome and neurotoxicity (see the Leukaemia, MPN and MDS chapter).

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Targeted Therapies

Targeted drugs block specific molecules that drive a cancer. They need biomarker testing first.

• EGFR inhibitors (EGFR-mutant lung cancer - osimertinib): Acne-like rash, diarrhoea, paronychia, ILD.
• ALK, ROS1, RET, KRAS G12C inhibitors (lung cancer): Variable side effects.
• Anti-VEGF drugs:
  • Bevacizumab, and TKIs such as sunitinib, pazopanib, cabozantinib, lenvatinib.
  • Hypertension, proteinuria, bleeding, bowel perforation, poor wound healing (stop before surgery), clots.
  • Hypothyroidism and hand–foot reactions (TKIs); liver toxicity (pazopanib).
• HER2-targeted drugs (breast, gastric): Trastuzumab - cardiotoxicity (echo every 3 months). Trastuzumab deruxtecan - ILD.
• BRAF and MEK inhibitors (BRAF-mutant melanoma, lung, thyroid): Fever, rash, skin cancers (BRAF alone), eye problems.
• PARP inhibitors (BRCA-mutant ovarian, breast, prostate and pancreatic cancer - olaparib, niraparib): Anaemia, nausea, fatigue; rare MDS and AML.
• CDK4/6 inhibitors (ER-positive breast cancer - palbociclib, ribociclib, abemaciclib): Neutropenia (usually without infection), ribociclib QT prolongation, abemaciclib diarrhoea.
• mTOR inhibitors (everolimus): Mouth ulcers, pneumonitis, high glucose and lipids.
• Antibody–drug conjugates - an antibody carries chemotherapy to cancer cells (e.g. trastuzumab deruxtecan, sacituzumab govitecan, enfortumab vedotin).
• Interactions: Many targeted tablets are broken down by CYP3A4 - check before adding drugs such as clarithromycin, azoles or St John's wort. Some need acid for absorption (avoid PPIs).

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Hormone Therapies

Breast cancer (ER-positive):

• Tamoxifen (pre- and postmenopausal):
  • Hot flushes.
  • VTE.
  • Endometrial cancer (investigate postmenopausal bleeding).
  • Cataracts.
  • It protects bone in postmenopausal women.
  • CYP2D6 inhibitors (fluoxetine, paroxetine) may reduce its effect - use other antidepressants (venlafaxine, citalopram).
• Aromatase inhibitors (anastrozole, letrozole, exemestane - postmenopausal, or premenopausal with ovarian suppression):
  • Joint pain.
  • Osteoporosis - DEXA, calcium and vitamin D; bisphosphonates.
  • Hot flushes; vaginal dryness.
• Ovarian suppression (goserelin) in premenopausal women.
• Fulvestrant - injections for advanced disease.
• Usually given for 5–10 years after early breast cancer.

Prostate cancer - androgen deprivation therapy (ADT):

• LHRH agonists (goserelin, leuprorelin):
  • These cause a testosterone "flare" in the first weeks - give an anti-androgen (bicalutamide) for about 3 weeks, starting before the first injection.
  • Especially important with spinal metastases (risk of cord compression) or urinary obstruction.
• LHRH antagonists (degarelix, relugolix) - no flare.
• Side effects of ADT:
  • Hot flushes; fatigue.
  • Loss of libido; erectile dysfunction.
  • Gynaecomastia.
  • Osteoporosis.
  • Weight gain, diabetes and cardiovascular risk.
  • Muscle loss; anaemia; mood and cognitive change.
• Newer hormonal drugs:
  • Abiraterone (with prednisolone) - hypertension, low potassium, fluid retention, liver toxicity.
  • Enzalutamide, apalutamide, darolutamide - fatigue, falls, seizures (rare), hypertension.
• Monitoring on ADT: BP, glucose, lipids, weight, bone health; exercise advice.

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Inherited Cancer Risk

• About 5–10% of cancers are due to a strongly inherited gene variant.
• Clues:
  • Several close relatives with the same or related cancers.
  • Young age at diagnosis.
  • More than one primary cancer in the same person.
  • Male breast cancer.
  • Ashkenazi Jewish ancestry (BRCA founder variants).
  • Specific tumour features (e.g. triple-negative breast cancer under 60, mismatch repair-deficient bowel cancer).
• Important syndromes:
  • BRCA1 and BRCA2 - breast, ovarian, prostate and pancreatic cancer.
  • Lynch syndrome - bowel, endometrial, ovarian, stomach, urinary tract.
  • Li–Fraumeni syndrome (TP53) - sarcomas, breast, brain, adrenal, leukaemia at young ages.
  • FAP - bowel polyposis.
  • MEN1 and MEN2; von Hippel–Lindau; PALB2; CDH1 (gastric and lobular breast).
• Testing: Through clinical genetics, or "mainstream" testing by the cancer team. Genetic testing of tumours can also reveal inherited variants.
• Managing high risk (e.g. NICE CG164 for familial breast cancer):
  • Enhanced screening (MRI, colonoscopy).
  • Risk-reducing surgery (mastectomy, removal of ovaries and tubes).
  • Chemoprevention (tamoxifen or anastrozole for women at moderate or high breast cancer risk; aspirin in Lynch syndrome).
  • Cascade testing of relatives.

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Cancer of Unknown Primary

• Malignancy of undefined primary origin (MUO) - metastatic cancer found without an obvious source. When a primary still isn't found after full investigation, it is called cancer of unknown primary (CUP).
• About 2–3% of cancers. Often presents late with liver, lung, bone or node metastases, or ascites.
• Initial tests (NICE CG104):
  • History and examination (breast, rectal, pelvic, testicular, skin).
  • FBC, U&E, LFTs, calcium, LDH, urinalysis.
  • CT chest, abdomen and pelvis.
  • Tumour markers if relevant (PSA in men, AFP and hCG for germ cell tumours, CA125 in women with ascites).
  • Biopsy with immunohistochemistry and molecular profiling.
• Don't miss treatable cancers:
  • Lymphoma.
  • Germ cell tumours (young men with midline nodes - check AFP and hCG).
  • Breast cancer (women with axillary nodes).
  • Prostate cancer (bone metastases, high PSA).
  • Ovarian cancer (peritoneal disease).
  • Neuroendocrine tumours.
  • Thyroid cancer.
• Management: Refer to the acute oncology or CUP team quickly. Balance investigation against the patient's fitness and wishes - not everyone needs every test. Treat by the most likely primary; prognosis is often poor.

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Cancer in Older People

• Over a third of cancers occur in people over 75. Age alone shouldn't decide treatment - fitness, frailty and wishes matter more.
• Geriatric assessment before major treatment:
  • Screening tools (e.g. G8) identify who needs a full comprehensive geriatric assessment.
  • Assess:
    • Function and mobility.
    • Falls.
    • Cognition (and delirium risk).
    • Mood.
    • Nutrition.
    • Other illnesses.
    • Polypharmacy.
    • Social support.
  • Chemotherapy toxicity tools (e.g. CARG) predict serious side effects.
• Benefits of assessment:
  • Reduces severe toxicity.
  • Improves treatment completion.
  • Picks up treatable problems (depression, malnutrition, falls risk).
• Practical points:
  • Reduced kidney function affects dosing.
  • Drug interactions with targeted drugs.
  • Higher risk of neutropenic sepsis (consider G-CSF).
  • Falls with neuropathy and hormone therapies.
  • Carer needs.
• Treatment can be adapted - shorter radiotherapy courses, lower-dose or single-agent chemotherapy, endocrine therapy instead of surgery in selected frail women with ER-positive breast cancer.
• Discuss goals - many older people prioritise independence and quality of life over length of life.

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Living With and Beyond Cancer

• About 3.5 million people in the UK are living with or after cancer.
• Late effects of treatment:
  • Heart - anthracyclines, trastuzumab, chest radiotherapy, ADT.
  • Second cancers - after radiotherapy and some chemotherapy.
  • Infertility, early menopause, sexual problems.
  • Bone loss - aromatase inhibitors, ADT, early menopause.
  • Peripheral neuropathy.
  • Lymphoedema after node surgery or radiotherapy.
  • Bowel and bladder problems after pelvic treatment.
  • Fatigue; cognitive problems.
  • Thyroid problems (neck radiotherapy, immunotherapy).
• Psychological effects: Fear of recurrence, anxiety, depression. Screen and support.
• Healthy lifestyle: Physical activity reduces fatigue and may reduce recurrence; stop smoking; healthy weight; limit alcohol.
• Follow-up: Often personalised stratified follow-up - patient-initiated, with clear guidance on which symptoms to report.
• Work and money: Return to work, financial support, travel insurance.
• Childhood cancer survivors need lifelong late-effects follow-up.

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Drug Reference Table

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Spot the Diagnosis

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Exam-style Scenarios

1. A 58-year-old on nivolumab for melanoma has 7 watery stools a day and abdominal pain.
Answer: Grade 3 immune-related colitis.

• Admit; stool cultures and C. difficile; contact acute oncology.
• Hold immunotherapy; IV methylprednisolone.
• Infliximab if no response in 48–72 hours; slow steroid taper.

2. A 70-year-old man with prostate cancer and spinal metastases is to start goserelin.
Answer: Risk of tumour flare.

• Start bicalutamide before the first injection and continue for about 3 weeks (or use a GnRH antagonist).
• Warn him to report back pain, leg weakness or urinary problems urgently.
• Monitor bone health, BP, glucose and lipids on ADT.

3. A woman on tamoxifen develops depression. Her GP wants to start fluoxetine.
Answer: Fluoxetine inhibits CYP2D6 and may reduce tamoxifen's effect.

• Use a different antidepressant (e.g. sertraline, citalopram or venlafaxine).

4. A 66-year-old has liver metastases on CT with no obvious primary. She is fit.
Answer: Malignancy of undefined primary origin.

• Refer to the acute oncology or CUP team.
• Breast and pelvic examination; CT chest, abdomen and pelvis; tumour markers (CA125, CA19-9, CEA, AFP).
• Liver biopsy with immunohistochemistry and molecular testing.

5. A 39-year-old woman has a mother with ovarian cancer at 48 and a sister with breast cancer at 36.
Answer: High risk of an inherited BRCA variant.

• Refer to clinical genetics for counselling and testing.
• If a carrier: MRI screening, discussion of risk-reducing surgery, and cascade testing of relatives.