Understanding the process of cancer metastasis

Throughout my career in oncology, I thought I was communicating difficult concepts to patients and families relatively well.  Recently, my wife and I visited our daughter in Salt Lake City over Thanksgiving.  Catherine is an extremely accomplished blogger and video broadcaster.  So when she commented on my blogs, I paid attention.  Her (constructive) criticism was my use of some medical terminology which she didn’t understand.  More surprising to me was the example she cited:  “metastasis.”   Like others I recalled in the past, she had trouble pronouncing the word.

My wife, Dee Dee, is a psychotherapist with training in psycho-oncology and hypnotherapy.  She is adept in psychosocial support for patients and families.  So when she spoke, I listened.  Hearing the above, her input was that many patients and family members have little understanding of what cancer is.  Since the ability to spread (metastasize) from the organ where cancer started to another organ or region of the body is what defines cancer (malignancy), and a benign growth does not have this capability, metastasis deserves further comment.

Cancerous cells can spread by one of three routes:

  1. By direct extension locally to adjacent structures.
  2. To regional lymph nodes that drain the primary organ.
  3. To sites distant from the original growth, implying spread through the bloodstream.

Using breast cancer as an example, fibro-adenoma is a benign growth that appears as a smooth, round lump felt on breast examination or visualized on mammography.  Contrast this with ductal carcinoma-in-situ (DCIS), which is malignant but is confined to the tubes connecting milk glands to the nipple which has not invaded into the surrounding breast yet.  DCIS usually presents with tiny calcium spots on mammograms, not an actual lump.  Finally, infiltrating (invasive) ductal carcinoma (IDC) appears as a breast lump usually hard and irregular that can spread by all three routes listed above.

The mainstay of treatment for over seven decades was the radical mastectomy as championed by William Halsted at Johns Hopkins in the 1890’s.  This procedure was based on the theory that breast cancer spread locally and to regional lymph nodes, mostly in the axilla (armpit), before it invaded into the bloodstream and spread to distant sites far from the breast itself.  Therefore, if the entire cancer was removed surgically with wide margins of normal tissue before the last event occurred, patients should be cured.  Likelihood of cure was also increased if lymph nodes were not involved yet.  In my training years, it was not uncommon for a woman to feel a lump, call her physician who admitted her to hospital that night for surgery the following morning, telling her that if she woke up without a breast she’d know she had cancer.

Analysis of 7 decades of experience with radical surgery revealed if a woman experienced a long remission she possibly did not need such a disfiguring operation; and conversely, if the disease had already spread through the bloodstream the procedure would be of no benefit.  To test these concepts, Dr. Bernard Fisher of the University of Pittsburgh, started a clinical trial comparing radical mastectomy with simple mastectomy or lumpectomy + radiation therapy.  Since benefits of all 3 procedures proved to be essentially equal, there was no need for radical procedures.  Also, whether or not regional lymph nodes were involved with metastases proved important in estimating prognosis.  If nodes were free of disease, 5 year disease free survival was 80%; if nodes contained metastases, this figure fell by about 30%.

But the question arose:  “If Halsted’s theory as to how breast cancer spread (first to lymph nodes, then to the systemic circulation) was correct, why weren’t 100% of women with node negative disease cured?”  This lead to the notion that some breast cancers have already metastasized at the time of diagnosis, and benefit could only be obtained by treating with something that permeated every organ in the body, i.e., chemotherapy, used as an “adjuvant” (to give a boost) to loco-regional treatments.

In conclusion, one of the reasons Halsted’s attempt to cure breast cancer with radical surgery failed was an incomplete understanding of the process of metastasis.  No amount of local therapy, be it surgery or radiation therapy or both would cure a patient whose malignant cells had bypassed regional lymph nodes and gained access to the systemic circulation.

Richard Just is an oncologist who blogs at @JustOncology.

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