In today’s article, we continue our focus on the tumors of epithelial origin, carcinomas. In the previous article, we discussed invasion of the cells through the basement membrane, declaring themselves as malignant, and the prevalence as well of the pathologic diagnosis of carcinoma-in-situ (CIS), a benign and relatively good diagnosis.
Today, we will go to the opposite extreme, metastasis. Metastasis is the spread of the cancer from the primary site of origin to another site, sometimes quite distant: for example a breast cancer cell spreading to the liver or bone to form a tumor there. The term comes from the Greek word for displacement.
The metastasis (or met, for short) is composed of cells from the original breast cancer and thus, in most respects, behaves in a similar fashion to the breast cancer in terms of response to therapeutic agents, and looks like breast cancer under a microscope. It is a common error to refer to a metastasis as a cancer of the organ in which it is located, e.g., to call a liver “met” a liver cancer, but if the met arose in the breast and metastasized to the liver, it is breast cancer that has metastasized, not a liver cancer.
Metastatic spread can occur in one of three ways. The tumor cells may gain access to the bloodstream (when they invade into the connective tissue where the blood vessels and lymphatics are) and then be carried to distant sites where they can settle and form new tumors.
Alternatively, they can also spread via the lymphatic system, a localized system of vessels that surround each organ and act as a sort of sewage system for each organ. If this lymphatic spread remains localized, it can frequently be resected and cured, but lymphatic spread can also reach more generalized pathways and lead to distant lymphatic spread.
A third way in which metastasis may occur is by simple migration of tumor cells along local membranes and surfaces. This occurs frequently in ovarian cancer, where ovarian cancer cells are shed into the pelvis and create tumors there, without necessarily having gained access to the bloodstream or lymphatic system. Occasionally, such localized metastases may be successfully treated with local measures and treatments.
Metastasis is important because it is responsible for probably 90% of the deaths stemming from solid tumors—carcinomas and sarcomas (bone and soft-tissue). Unfortunately for most of these tumors with metastatic cancer—most, not all—cure is not usually possible. Various treatments—usually systemic therapies like chemotherapy, hormonal therapy and immunotherapy—can provide significant and even dramatic life prolongation for most such cancers, but cures are very infrequent. Recently, surgical approaches have been able to treat some patients with limited metastatic colorectal cancer with curative results. Likewise, radiotherapy has a role to play for limited metastatic disease.
For patients diagnosed with localized nonmetastatic cancers, the goal of therapy is to eradicate the cancer before metastasis can occur. The backbone of such treatment is localized therapy with surgery and/or radiotherapy, but the recent trend has been to supplement these treatments with the addition of systemic treatment so as to improve the probability that metastasis will not develop later.
Fortunately, the large majority of patients with carcinomas are diagnosed with nonmetastatic cancer; the increased use of early detection has ameliorated these statistics. For breast cancer, for example, only about 5-6% are diagnosed as stage IV, the designation for metastatic disease. Approximately 20% of colorectal cancer is stage IV at diagnosis. For prostate cancer, the figure is about 4%. It should be borne in mind that these are just the figures at the initial time of diagnosis—unfortunately, the majority of metastases are detected subsequent to the initial diagnosis.
A popular model to describe the process of metastasis was promulgated in 1928 by Stephen Paget and called the “Seed and Soil” theory. It attempts to explain the non-random distribution of metastases.
Each cancer tends to metastasize in a certain pattern—prostate cancer preferentially metastasizes to bone, sarcomas to lung, colorectal cancer to liver, and so on. These patterns are not exclusive—tumors can and do metastasize elsewhere but have a predilection for these sites and this is thought to stem from either the pattern of the anatomical blood and lymphatic pathways that carry the tumor cells, or from characteristics of the cancer cells and the organ site that predispose them to be more “fertile” in certain locations, to use an agricultural analogy.
It is also clear that the primary tumor releases many cancer cells into the bloodstream along the way (“seeds”), but that only a very few ultimately do find “fertile” soil and establish metastatic tumors. New technology has enabled us to identify so-called circulating tumor cells (CTCs) in the blood of patients with cancer, and this information is slowly being incorporated into clinical practice.
In the book of Tehillim, we read, “So teach the number of our days so we shall acquire a heart of wisdom.” (90:12) I don’t know if it is good to know how long you will live, but it is naturally a common inquiry among cancer patients—the answer to that query is primarily dependent, again focusing on carcinomas, on the likelihood of metastasis. We will address this question in the next installment of Thoughts on Cancer.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
