Cancer Treatment Modalities

Cancer therapy is delivered across three main pillars — surgery, radiation, and systemic therapy — often combined in multimodal regimens.

Surgery remains the cornerstone of solid tumour treatment. Curative-intent surgery aims to remove the primary tumour with clear margins (R0 resection — no residual tumour microscopically). Positive margins (R1 = microscopic residual, R2 = gross residual) significantly increase local recurrence risk. Margins are cancer-specific: 1 cm wide local excision suffices for thin melanoma; total mesorectal excision with circumferential radial margins is critical in rectal cancer. Palliative surgery relieves symptoms without curative intent — for example, colonic stenting for obstruction or mastectomy for ulcerating tumour. Sentinel lymph node biopsy (SLNB), developed in the 1990s, maps the first-draining (sentinel) node via peritumoral injection of blue dye or radiocolloid. If the sentinel node is tumour-free, formal nodal clearance is avoided, reducing lymphoedema risk.

Radiation therapy (RT) delivers ionising radiation to cause DNA double-strand breaks, predominantly killing rapidly dividing tumour cells. External beam RT (EBRT) is delivered via linear accelerator (LINAC) using photon or proton beams. Stereotactic radiosurgery (SRS, e.g., Gamma Knife, CyberKnife) delivers ablative dose to small targets in 1–5 fractions, used in brain metastases and early lung cancer. Brachytherapy places sealed radioactive sources directly within or adjacent to tumour — used in cervical cancer (intracavitary) and prostate cancer (permanent seed implants). Common side effects: fatigue, mucositis, dermatitis (skin within field), and late effects including fibrosis, secondary malignancy, and organ-specific damage (pneumonitis, proctitis, neurocognitive effects).

Chemotherapy exploits the cell cycle to preferentially kill dividing cells. Cell cycle phases: G0 (quiescent), G1 (growth, RNA/protein synthesis), S (DNA synthesis), G2 (further growth, repair), M (mitosis). Alkylating agents (cyclophosphamide, cisplatin, carboplatin) cross-link DNA strands, blocking replication — phase-nonspecific. Antimetabolites (methotrexate, 5-fluorouracil, gemcitabine) are structural analogues that inhibit nucleotide synthesis or incorporate into DNA/RNA — S-phase specific. Taxanes (paclitaxel, docetaxel) stabilise microtubules, blocking mitotic spindle disassembly — M-phase specific. Vinca alkaloids (vincristine, vinblastine) bind tubulin and prevent polymerisation, also blocking M phase.

Targeted therapies exploit specific oncogenic drivers. Imatinib (Gleevec) inhibits the BCR-ABL tyrosine kinase produced by the Philadelphia chromosome in CML — the prototype of targeted therapy, transforming CML from a fatal disease to one manageable chronically. Trastuzumab (Herceptin) is a monoclonal antibody targeting HER2 receptor in HER2-amplified breast cancer (approximately 15–20% of cases), improving survival dramatically. BRAF inhibitors (vemurafenib, dabrafenib) target the BRAF V600E mutation present in ~50% of cutaneous melanomas; combined with MEK inhibitors (trametinib) to delay resistance.