19.5 — The Common Cancers, One by One

Four cancers — lung, breast, colorectal and prostate — account for around 40 percent of all cases.

And their outlooks differ enormously, which is the point of covering them individually rather than as a category.

Lung cancer

The leading cause of cancer death worldwide, and the one where prevention matters most.

Around 85 percent is caused by smoking. And the risk falls substantially after stopping — around half within 10 years — though it never returns fully to that of a never-smoker.

Two main types:

Non-small cell (around 85 percent) — adenocarcinoma, squamous, and large cell.

And adenocarcinoma is the commonest type in never-smokers, which matters because lung cancer in a non-smoker is frequently not considered.

Small cell (around 15 percent) — aggressive, almost always in smokers, frequently disseminated at diagnosis, initially very responsive to chemotherapy and then relapsing.

Symptoms: persistent cough or a change in a chronic cough, coughing blood, breathlessness, chest pain, weight loss, recurrent chest infections.

And frequently the presentation is from spread or from a paraneoplastic syndrome (Chapter 19.3) — a hoarse voice from recurrent laryngeal nerve involvement (Chapter 3.6), a seizure from a brain metastasis, or low sodium.

What has changed, substantially:

Molecular subtyping. Around 30 to 50 percent of adenocarcinomas in never-smokers carry a targetable driver mutation — EGFR, ALK, ROS1 and others — and the matching drugs produce far better responses than chemotherapy (Chapter 19.2).

Immunotherapy, which has produced long-term survival in a subset of patients with advanced disease.

And screening. Low-dose CT screening in high-risk smokers and ex-smokers reduces lung cancer mortality by around 20 percent, established in the NLST and NELSON trials. Programmes are being introduced in several countries, and it is the first effective lung cancer screening after decades of failed attempts with chest X-ray.

Five-year survival remains around 20 percent overall — driven by late presentation — and over 60 percent for stage I disease. Which is exactly what screening addresses.

Breast cancer

The commonest cancer in women worldwide, and one of the success stories.

Five-year survival now exceeds 85 percent in most high-income countries, and over 95 percent for early-stage disease.

Risk factors: age; female sex — though around 1 percent of cases occur in men; early menarche and late menopause, both increasing lifetime oestrogen exposure; not having children, or later first pregnancy; not breastfeeding; HRT; alcohol; obesity after menopause; and family history and BRCA mutations.

And the protective factors are the mirror image: pregnancy, breastfeeding, and physical activity.

Presentation: a lump — usually painless, hard and irregular; skin dimpling or puckering; nipple retraction or change in direction; bloody or clear discharge from one duct; a persistent rash on the nipple; and axillary lymph nodes (Chapter 15.3).

And the great majority of breast lumps are benign. Triple assessment — examination, imaging and needle sampling — establishes which quickly.

Subtypes determine treatment entirely (Chapter 19.4): hormone-receptor status, HER2 status, and triple-negative disease.

Treatment combines surgery — and breast-conserving surgery with radiotherapy gives equivalent survival to mastectomy for suitable tumours, which was a major finding — radiotherapy, hormonal treatment for 5 to 10 years, chemotherapy where indicated, and HER2-targeted therapy.

Screening — mammography, typically from 50, reduces breast cancer mortality by around 20 percent.

And it also produces overdiagnosis — detecting cancers that would never have caused harm (Chapter 16.1). The honest position is that screening saves lives and that some women are treated for cancers that would never have troubled them, and that the balance is a genuine judgement rather than a settled fact. Informed choice, with the actual numbers, is the right approach.

Colorectal cancer

Third commonest, and among the most preventable.

Because it almost always arises from a polyp — an adenoma — that takes 10 to 15 years to become malignant.

Which is why screening does something unusual: it prevents cancer rather than only detecting it. Removing a polyp prevents the cancer it would have become.

Screening reduces colorectal cancer mortality by around 15 to 30 percent, and reduces incidence as well — which is a stronger claim than any other screening programme can make.

Methods: faecal immunochemical testing (FIT) every 1 to 2 years, and colonoscopy every 10 years. Both work; uptake determines which performs better in practice.

Risk factors: age; family history; inflammatory bowel disease; Lynch syndrome and familial adenomatous polyposis; obesity; physical inactivity; smoking; alcohol; processed meat; and low fibre.

Symptoms: a persistent change in bowel habit, particularly looser and more frequent; rectal bleeding; abdominal pain; unexplained iron deficiency anaemia; and weight loss (Chapter 9.7).

And iron deficiency anaemia in a man or a postmenopausal woman means investigating the bowel (Chapter 7.1).

Treatment: surgery, with chemotherapy for node-positive disease, and radiotherapy for rectal cancer.

And a notable feature: liver metastases can be cured. Surgical removal of limited liver deposits produces five-year survival of around 40 to 50 percent, which is why isolated liver metastases are assessed for resection rather than assumed incurable (Chapter 19.3).

Rising incidence in people under 50 is a genuine and unexplained trend in several countries, and it has led to lowering the screening start age in some.

Prostate cancer

Commonest cancer in men in many countries, and the one where the diagnostic question is hardest (Chapter 15.1).

Because most men who have it die of something else. Post-mortem studies find it in around 30 percent of men over 50 and 70 percent over 80.

So the challenge is distinguishing the cancers that matter from those that do not.

Symptoms are usually absent in early disease. Urinary symptoms are far more often from benign enlargement (Chapter 10.5). Bone pain can be the presenting feature of advanced disease.

PSA screening is genuinely contested, and the reason is overdiagnosis and overtreatment rather than the test being useless.

What has improved the situation substantially:

MRI before biopsy — identifying who needs one and targeting it, which reduces unnecessary biopsies and reduces detection of insignificant cancers.

Active surveillance — monitoring low-risk cancers with PSA, MRI and repeat biopsy rather than treating. It is now standard for low-risk disease, and it resolves much of the overtreatment problem.

Treatment for significant disease: surgery, radiotherapy, hormonal treatment — androgen deprivation, exploiting the dependence on testosterone (Chapter 12.6) — and newer agents in advanced disease.

Side effects are the central trade-off: incontinence and erectile dysfunction after surgery or radiotherapy, and the metabolic and quality-of-life effects of hormonal treatment.

Five-year survival exceeds 95 percent for localised disease.

Skin cancer

Chapter 14.5, and the essentials.

Basal cell carcinoma — commonest cancer of all, essentially never metastasises, cured by excision.

Squamous cell carcinoma — can spread, higher risk on lip and ear and in immunosuppression.

Melanoma — responsible for most skin cancer deaths.

And early melanoma has over 95 percent five-year survival while advanced melanoma had, until a decade ago, under 10 percent.

That gap is why ABCDE and the ugly duckling sign are worth knowing.

And the change in advanced disease is the largest in modern oncology (Chapter 19.7).

The blood cancers

Leukaemia — of the blood-forming cells.

Acute lymphoblastic leukaemia — mainly children. Cure rates now over 90 percent, from under 10 percent in the 1960s. One of the outstanding achievements of modern medicine, achieved through combination chemotherapy protocols refined over decades of clinical trials.

Acute myeloid leukaemia — mainly adults, harder, with cure rates around 35 to 40 percent under 60.

Chronic myeloid leukaemia — the BCR-ABL story (Chapter 2.7). Median survival from around five years to near-normal, on a daily tablet.

Chronic lymphocytic leukaemia — often indolent, frequently found incidentally, and many patients never need treatment.

Lymphoma — of lymphoid tissue.

Hodgkin lymphoma — cure rates above 85 percent, and over 90 percent in early stage. A cancer that primarily affects young adults and is usually curable.

Non-Hodgkin lymphoma — a large family ranging from indolent to highly aggressive. And counter-intuitively, the aggressive ones are frequently curable and the indolent ones are not — because chemotherapy targets dividing cells.

Myeloma — of plasma cells. Bone pain, fractures, anaemia, kidney impairment and high calcium. Not curable, and survival has improved dramatically — from around 2 to 3 years to over 7 to 10 with modern combinations.

Others worth knowing

Pancreatic — the most difficult, with five-year survival around 10 percent. Late presentation, because symptoms are vague until the tumour obstructs the bile duct (Chapter 9.5). Smoking is the main modifiable risk factor.

Ovarian — vague symptoms — bloating, early fullness, pelvic discomfort, urinary frequency — which is why it is diagnosed late. Persistent new symptoms of that kind in a woman over 50 warrant investigation. Screening has not been shown to reduce mortality.

Cervical — almost entirely preventable by HPV vaccination and screening (Chapter 15.13), and on course for elimination.

Endometrial — presents early with postmenopausal bleeding, which is why outcomes are relatively good. Any bleeding after menopause requires investigation.

Bladder — painless visible blood in the urine is the classic presentation, and it always warrants investigation. Smoking is the main risk factor.

Kidney — increasingly found incidentally on scans done for other reasons.

Oesophageal — progressive difficulty swallowing, solids before liquids (Chapter 9.1). Risk factors: reflux and Barrett's for one type; smoking and alcohol for the other.

Stomach — falling incidence, from refrigeration and H. pylori reduction (Chapter 9.2).

Liver — mainly from hepatitis B, hepatitis C and cirrhosis, and increasingly from fatty liver disease. Preventable by vaccination and by curing hepatitis C (Chapter 17.10).

Brain tumours — headache worse in the morning, seizures, focal deficits, personality change. Glioblastoma remains among the most difficult cancers, and molecular classification has improved prognostication and treatment selection.

Thyroid — usually excellent prognosis, and the overdiagnosis problem in Chapter 12.3.

The symptoms that warrant checking

A consolidated list, and none of them usually means cancer.

A new lump anywhere.Unexplained weight loss.A change in bowel habit lasting more than a few weeks.Blood — in stool, urine, sputum, or vaginal bleeding after menopause or between periods.A persistent cough or hoarse voice beyond three weeks.Difficulty swallowing.A mole that is changing.A sore that does not heal.Unexplained night sweats.Unexplained persistent pain.And unexplained fatigue with any of the above.

The great majority have benign explanations. The purpose of checking is that the small minority that do not are far more treatable when found early, and the difference between stage I and stage IV is frequently the difference between cure and management.

What the next page fixes

Chapter 19.6 covers screening — which programmes work, which do not, and how to think about being offered a test for a disease you do not have.