19.7 — Cancer Treatment

In 2010, a person with metastatic melanoma had a median survival of around six to nine months, and essentially nothing worked.

Today, a substantial proportion of those patients are alive five and ten years later, and a meaningful number appear to be cured.

That change came from releasing a brake on the immune system, and it is the largest single advance in cancer treatment in this century.

Surgery

Still the most likely to cure, and around half of all cancers cured are cured by surgery alone.

And its direction has been toward less.

Breast-conserving surgery with radiotherapy gives equivalent survival to mastectomy for suitable tumours — established by long-term trials, and a substantial reduction in what patients undergo.

Sentinel node biopsy rather than full node clearance (Chapter 7.8).

Laparoscopic and robotic surgery — smaller incisions, faster recovery, equivalent oncological outcomes for many procedures.

Organ preservation — bladder, larynx and limb-preserving approaches replacing removal in selected cases.

Surgery also has non-curative roles: relieving obstruction, controlling bleeding, and stabilising bones at risk of fracture.

Radiotherapy

Ionising radiation damaging DNA, so that cells die when they next attempt to divide (Chapter 1.7).

Around half of all cancer patients receive it.

Why it is given in many small fractions rather than one large dose: normal tissue repairs DNA damage between sessions better than tumour tissue does, so fractionating widens the gap between killing the tumour and killing the patient.

Modern techniques have substantially reduced collateral damage:

Intensity-modulated radiotherapy — shaping the dose to the tumour.

Stereotactic radiotherapy — very high doses to a small precisely defined target in a few sessions. Used for brain metastases and for small lung tumours, with results approaching surgery in some settings.

Proton therapy — protons deposit most of their energy at a defined depth and then stop, rather than continuing through. Which spares tissue beyond the target — particularly valuable in children and in tumours near critical structures. Its benefit over modern photon therapy in adults is more contested than the marketing suggests.

Brachytherapy — a radioactive source placed inside or against the tumour.

Side effects are largely local and depend on what is in the field: skin reactions, mucositis, diarrhoea, fatigue. Fatigue is near-universal, cumulative, and consistently underestimated.

Late effects — fibrosis, second cancers years later, and effects on growth in children — are the reason paediatric radiotherapy is minimised.

Chemotherapy

Drugs that kill dividing cells (Chapter 1.7), and its side effect profile follows entirely from that.

Hair loss, mucositis, nausea and diarrhoea, and low blood counts — because hair follicles, gut lining and bone marrow are the fastest-dividing normal tissues.

And marrow suppression is usually what limits the dose.

Classes: alkylating agents; platinum drugs; antimetabolites; taxanes and vinca alkaloids, which act on microtubules (Chapter 1.5); and topoisomerase inhibitors.

Given in cycles — allowing normal tissue to recover between doses.

And in combinations — different mechanisms, non-overlapping toxicities, and reduced resistance. The principle that produced the cures in childhood leukaemia and Hodgkin lymphoma.

What has genuinely improved the experience:

Antiemetics. Modern combinations control nausea in the large majority, where it was previously the symptom patients dreaded most and a common reason for stopping treatment.

Growth factors to shorten the period of low neutrophils.

Scalp cooling to reduce hair loss (Chapter 14.3).

And better selection. Gene expression tests identify people who will not benefit and can safely avoid it (Chapter 19.4) — thousands each year.

Neutropenic sepsis remains the main danger (Chapter 17.11). Fever on chemotherapy is an emergency: antibiotics within the hour, before any results. Every patient is given a card and a number to call, and it is one of the most important pieces of information they receive.

Hormonal therapy

For cancers that depend on hormones.

Breast — tamoxifen blocks the oestrogen receptor; aromatase inhibitors block oestrogen production (Chapter 12.6). Taken for 5 to 10 years, and the extended duration reduces late recurrence.

Prostate — androgen deprivation, by injection or by newer oral agents blocking the receptor or its synthesis.

Effective, well tolerated relative to chemotherapy, and with their own consequences — menopausal symptoms and bone loss in one case, and metabolic and quality-of-life effects in the other.

Targeted therapy

Drugs designed against a specific molecular abnormality (Chapter 19.2).

Small molecule inhibitors — usually oral, ending in -inib. Imatinib, erlotinib, palbociclib.

Monoclonal antibodies — injected, ending in -mab. Trastuzumab, rituximab, bevacizumab (Chapter 13.3).

Antibody–drug conjugates — an antibody carrying a chemotherapy payload, delivering it to cells displaying the target and largely sparing others. These have produced substantial gains in breast, bladder and lung cancer, and they are among the most active areas of development.

PARP inhibitors — synthetic lethality in BRCA-mutant cancers (Chapter 2.5).

The requirement is a target, which is why molecular testing now precedes treatment decisions.

And the limitation is resistance, which emerges predictably because the tumour is an evolving population (Chapter 19.1).

Immunotherapy

And this is where the largest change has come.

Checkpoint inhibitors — blocking the "off switches" on T cells that tumours exploit (Chapter 19.2).

They do not attack the tumour. They release a response that was already present and being suppressed.

Which explains their two most distinctive features.

Responses can be extraordinarily durable. Unlike chemotherapy, where the effect ends when the drug stops, an immune response has memory (Chapter 13.5). A proportion of responders remain in remission years after stopping treatment, which is why the word "cure" is being used cautiously about metastatic disease for the first time.

And the side effects are autoimmune. Releasing the brakes releases them everywhere — colitis, hepatitis, pneumonitis, thyroid and pituitary dysfunction, skin reactions, and occasionally type 1 diabetes or myocarditis.

These are managed with steroids and, importantly, they need to be recognised. A patient on immunotherapy with new diarrhoea has immune colitis until proven otherwise, and treating it as an infection wastes critical time.

Where they work best: melanoma, non-small cell lung cancer, kidney, bladder, head and neck, Hodgkin lymphoma, and any tumour with mismatch repair deficiency (Chapter 2.2).

Where they work poorly: "cold" tumours with few mutations and little immune infiltration — pancreatic and prostate cancer among them.

CAR-T cell therapy — a patient's own T cells are removed, genetically engineered to carry a receptor recognising their cancer, expanded, and returned.

Remarkable results in some blood cancers — complete response rates around 50 to 90 percent in refractory leukaemias and lymphomas, in patients who had exhausted everything else.

Its problems: cytokine release syndrome — a massive inflammatory response, treatable with a specific antibody; neurological toxicity; the manufacturing time; the cost; and limited success so far in solid tumours, which is the current frontier.

Cancer vaccines — therapeutic rather than preventive, and individualised mRNA vaccines based on a patient's own tumour mutations are in trials with encouraging early results in melanoma.

Bispecific antibodies — gripping a T cell with one arm and a cancer cell with the other, dragging them together (Chapter 13.3).

Bone marrow transplantation

High-dose treatment destroying the marrow, followed by stem cell rescue.

Autologous — the patient's own cells, allowing higher doses.

Allogeneic — donor cells, and the therapeutic effect comes substantially from the donor immune system attacking residual cancer — the graft-versus-leukaemia effect (Chapter 13.8).

Which is why some graft-versus-host disease is associated with lower relapse rates, and why the balance is so delicate.

Supportive and palliative care

And this deserves emphasis, because the evidence is stronger than its reputation.

Early palliative care alongside active treatment improved quality of life, reduced depression — and, in a landmark trial in metastatic lung cancer, improved survival.

Patients receiving early palliative care lived around two to three months longer than those receiving standard oncology care alone, despite receiving less aggressive treatment at the end of life.

Which reframes it entirely. Palliative care is not what happens when treatment stops. It is symptom control, communication and support delivered alongside treatment, and referring early is a clinical decision rather than an admission of defeat.

Pain control — the majority of cancer pain can be controlled, using a stepped approach from simple analgesia to opioids, plus adjuvants for neuropathic pain (Chapter 11.13).

And the fear of opioid addiction in cancer pain is largely misplaced, and undertreatment of cancer pain remains common — particularly in low-income countries where opioid availability is restricted.

Clinical trials

Worth explaining, because a substantial proportion of patients could join one and do not know it.

Phase 1 — safety and dose, usually in patients who have exhausted standard options. Phase 2 — does it work? Phase 3 — is it better than current standard treatment?

And the common misconception is that trial participants risk receiving no treatment. Placebo-only arms are rare in cancer. The comparison is almost always the current best standard treatment, with the new agent added or substituted.

Trial participants generally do at least as well as those receiving standard care, partly from the treatment and partly from the intensity of monitoring.

Asking whether there is a trial is a reasonable question at every stage.

What treatment cannot do

And this belongs in a chapter about treatment.

Some cancers remain very difficult — pancreatic, glioblastoma, and several others.

Resistance is near-universal in advanced disease with single-agent targeted treatment.

Cost and access are substantial barriers, and the gap between what exists and what is available differs enormously by country.

And there is a point at which further anti-cancer treatment causes more harm than benefit. Recognising it and saying so plainly is part of good care, and the evidence is that patients want that conversation earlier than they usually get it.

What the next page fixes

Chapter 19.8 closes this Part with the questions patients actually ask — about prognosis, about living with it, and about what happens afterwards.