OncologyTier 2Topic

Processes of - metastatic spread

Definition

Metastasis - the spread of malignant cells from a primary tumour to establish growth at a distant site - is the process responsible for the great majority of cancer deaths, not the primary tumour itself in most solid cancers
The propensity and pattern of metastasis varies substantially by tumour type, reflecting both mechanical factors (venous drainage) and biological "seed and soil" compatibility between tumour cells and the target organ

The invasion-metastasis cascade: local invasion through the basement membrane -> intravasation into blood/lymphatic vessels -> survival in circulation (most circulating tumour cells die here - a major bottleneck) -> extravasation at a distant site -> colonisation (establishing a growing deposit, often the hardest step, with many cells remaining as dormant micrometastases for years before growing)
Epithelial-mesenchymal transition (EMT) - epithelial tumour cells downregulate cell-adhesion proteins (e.g. E-cadherin) and adopt a more motile, invasive mesenchymal phenotype to begin the invasion process - often partially reversed (mesenchymal-epithelial transition) once the cell establishes itself at the distant site

Route predicts pattern: haematogenous spread follows venous drainage (colorectal cancer -> portal vein -> liver; most systemic tumours -> vena cava -> lungs first); lymphatic spread follows regional lymph node drainage chains (the basis of sentinel lymph node biopsy); transcoelomic spread seeds directly across a body cavity (ovarian cancer -> peritoneal surfaces)
The "seed and soil" hypothesis explains organ-specific metastatic patterns beyond simple mechanical/anatomical drainage (e.g. breast cancer's specific propensity for bone, brain, and liver) - the target organ's microenvironment must be receptive, not just anatomically reachable

Understanding the dominant spread route for a given cancer directs staging investigations (sentinel node biopsy for lymphatic-spread cancers, liver imaging for portal-drained GI cancers) and, increasingly, targeted therapy against specific steps of the cascade

Sentinel lymph node biopsy (breast cancer, melanoma), organ-specific metastatic patterns (bone/brain/liver in breast cancer; liver in colorectal cancer; lung in most cancers via haematogenous spread), dormancy and late recurrence

Dormant micrometastases can remain clinically silent for years to decades before reactivating and growing - the biological basis for late recurrence seen in some cancers (e.g. oestrogen receptor-positive breast cancer, which can recur 10-20 years after apparently successful initial treatment) long after the patient is considered clinically cured

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