Why does metastasis prefer some organs?

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The main points of this article:

• Metastasis is a multi-step cascade; not every cell that enters the circulation seeds and grows.
• Seed–soil (Paget): the cell (seed) + the organ microenvironment (soil).
• Anatomic route (Ewing): blood/lymph flow sets the path; both views are read together.
• Colon → liver: the portal vein is an anatomic filter; distal rectum systemic drainage can raise lung tropism.
• In suitable patients surgery is central to local control; distant follow-up follows known organ tendencies.

The metastatic cascade (step by step)

As in the left panel of the schematic, spread is often told in these steps:

• Local invasion: Cells leave the primary tumor, breach surrounding stroma and basement membrane.
• Intravasation: Cells enter blood or lymph vessels as circulating tumor cells (CTCs).
• Survival in circulation: They resist shear stress and immune clearance while traveling.
• Extravasation: They exit capillary beds of distant organs into tissue.
• Colonization and growth: In a receptive microenvironment, angiogenesis can turn micro-foci into clinical masses.

Sources: Fidler 2003; Hanahan & Weinberg 2011.

The seed and soil hypothesis

Why spread tends toward certain organs — not purely at random — is explained by two classic views:

• Seed–soil (Stephen Paget, 1889): The cancer cell is the seed; the target organ microenvironment is the soil. The seed grows only where the soil supports it.
• Anatomic / hemodynamic route (James Ewing, 1920): The direction of blood and lymph flow largely sets the path.

Modern oncology keeps both: anatomy dictates the route of traffic; the microenvironment dictates survival and outgrowth.

Common organ tendencies (examples)

These are clinically familiar tendencies — not every patient’s map:

• Breast — bone, lung, liver, brain
• Prostate — bone
• Lung — brain, bone, adrenal gland
• Colon / pancreas — liver, peritoneum
• Colorectal overall — liver, lung

Colon → liver: the portal vein route

Venous blood returning from the intestines is filtered by the liver via the portal vein before joining the systemic circulation. That anatomic pathway helps carry colorectal cancer cells to the liver first — a tendency, not a certainty. Distal rectum exception: lower rectal drainage also reaches the systemic vena cava; so lung metastases are discussed more often in distal rectal cancers than in proximal colon disease. Regional lymph nodes (N) and distant organ metastasis (M) are usually separate staging categories.

Sources: Fidler 2003; Hanahan 2011 / 2022.

Garden and seed analogy

Wind (blood flow) carries the seed; the seed sprouts only in a receptive garden (soil). Removing the primary tumor with clear margins supports local control; distant-organ follow-up uses imaging guided by known tropism. Clear margins do not automatically zero distant risk — and “surgery is pointless because metastasis is possible” is also wrong.

Is surgery enough? When are distant foci discussed?

For many patients, surgical control of the primary is the foundation of a plan that aims to eliminate disease. Surgery alone does not zero distant risk. A small number of distant foci (oligometastasis) may, in selected patients, be treated with surgery or other local therapies. The decision depends on tumor type, number and site of foci, overall condition, and the team.

• Removing the primary is often the main path to local control.
• Follow-up plans follow the primary tumor’s known spread tendencies.
• Selected distant foci may be treated locally; not every metastasis is operated.

What science knows

Points that are firmly accepted:

• Metastasis is multi-step; most circulating cells do not seed.
• Organ tropism matches clinical observation; pure randomness is overstated.
• Seed–soil and anatomic route are read together.
• In colorectal tumors the portal vein partly explains liver tropism.
• Regional nodes and distant organ metastasis are usually separate in staging.

Not yet settled (do not overstate)

These claims are overstated or not generalizable to every patient:

• Saying every tumor has one universal “preference gene” is overstated.
• Saying “it will definitely go to that organ” is overstated.
• Saying the portal route means every colorectal patient gets liver metastasis is overstated.
• Saying “metastasis means never a curative plan” is overstated; selected local therapy may be discussed.