63 WHAT IS CANCER?
John A. Ridge M.D., Ph.D.

1. What is a neoplasm?

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A neoplasm is a new growth of tissue (tumor) in which cells grow progressively under conditions that do not prompt the growth of normal cells. A malignant neoplasm (cancer) is composed of cells that invade other tissues and spread.

2. What kinds of cancers are there?

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Malignant tumors of epithelial (surface tissue) cells are carcinomas. Malignant tumors of mesenchymal (connective tissue) cells are sarcomas. Carcinomas and sarcomas are solid tumors. Hematologic malignancies, such as leukemia, are liquid tumors of mesenchymal origin.

3. What about skin cancers?

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Most basal cell and squamous skin cancers are life-threatening only if neglected. They occur in tremendous numbers and are seldom fatal with proper treatment. Although the general principles of cancer management apply to skin cancers, they usually are not considered in the same class with other solid tumors.

4. Why is cancer bad for you?

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There is no simple answer. The replacement of normal tissue by tumor eventually causes organ dysfunction. If a tumor outgrows its blood supply and becomes necrotic, local inflammation ensues. Often obstruction (with compromise of the lumen) of the gastrointestinal tract, bile ducts, or airway develops as the tumor grows. Occasionally the cancer bleeds (but life-threatening bleeding is rare). Nerve invasion or inflammation typically cause pain, which may be excruciating. Cancers also may elaborate humoral factors (e.g., gastrin) that cause symptoms.

5. Are all cancers life-threatening?

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Cancer is a fatal disease. It is uncommon for a patient with an untreated cancer to die of something else. Currently more than 50% of patients with cancer in the United States are cured.

6. How do cancers start?

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No one knows, but cells begin to grow under circumstances when they should not. They stop responding to antigrowth signals, promote their own blood supplies, are seemingly able to replicate endlessly, and do not undergo programmed cell death (apoptosis).

7. Is this process the same for all cancers?

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No, the order in which these changes take place seems to vary among types of cancer and even between individual tumors with the same histologic type. Occasionally, a single mutation alone causes cancer, but many genetic alterations are usually involved.

8. Do all cancers spread?

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About 25% of patients with solid tumors have detectable metastases at the time of diagnosis. Fewer than 50% of the remainder develop metastases during the course of treatment. At diagnosis, a cancer is usually at least 1 cm in diameter (and often much larger), containing millions of cells. It is surprising that metastases have not occurred in all patients at the time of diagnosis.

9. How does cancer spread?

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Most cancer cells that enter the bloodstream or lymphatics do not cause metastases. Only rare malignant cells actually survive to cause distant tumor implants by recruiting new blood vessels. Many cells do not seem to come to rest in tissues conducive to their growth. Perhaps others are extirpated by the immune system.

10. Does this process have an effect on how surgeons treat patients with cancer?

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Operations to treat benign conditions are designed to remove as little tissue as possible while creating a new and desirable physiologic or anatomic state. Cancer operations, on the other hand, are designed to remove as much tissue as possible while leaving the patient with acceptable function. Cancer operations typically remove the primary tumor as well as the lymph nodes draining the primary site. Surgical resection is the single most effective treatment for solid tumors.

11. Why are lymph nodes removed during cancer operations?

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More than 100 years ago, William S. Halsted (if you don’t know the answer to any historical question posed on rounds, you should always guess “Halsted”) appreciated that tumor recurrence on the chest wall after mastectomy was related to tumor in remaining lymph nodes. Halsted believed that cancer of the breast spread in an orderly fashion (or perhaps even contiguously) from the primary tumor to regional lymph nodes and eventually to distant sites. He popularized en bloc dissection of the breast with axillary lymph nodes for treatment of breast cancer. Conceptually, this approach was adopted for surgical treatment of most solid tumors.

12. What is a sentinel lymph node?

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Sentinel lymph nodes are the first stop for tumor cells metastasizing through lymphatics from the primary tumor. Often there is more than one sentinel node, even for a small tumor. If no tumor is present in a sentinel lymph node, it is unlikely that tumor is present in any of the other nodes. Sentinel lymph node mapping has been used for cancers of many organs (including the skin, breast, colon, thyroid, and head and neck neoplasms). Careful evaluation of sentinel lymph nodes has proven reliable in the staging of melanoma. It will probably prove equally successful in managing breast cancer and head and neck tumors, sparing many patients far more morbid lymphadenectomies (lymph node dissections).

13. Do solid tumors spread in an orderly way?

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Not necessarily. Another view of breast cancer behavior became popular by the 1970s. Bernard Fisher postulated that cancer is widespread at its inception. He stated that “breast cancer is a systemic disease … and that variations in effective local regional treatment are unlikely to effect survival substantially.”

14. How do these different models of cancer affect treatment?

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Surgeons who believe that tumors spread in an orderly way tend to perform complete lymph node dissections in concert with resection of the primary tumor. They generally believe that lymphadenectomy will cure some patients who have lymph node involvement without distant metastases and that local recurrence is a preventable cause of death. Surgeons who believe that lymph node metastases are simply markers for systemic disease are usually far less aggressive in performing lymph node dissections because (in their view) removal of lymph nodes that contain tumor will not cure patients who probably already have metastatic disease.

15. Do we know which model is correct?

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Both are probably inadequate. Some solid tumors (e.g., squamous cancer of the head and neck, colon cancer) often have no distant disease, even when they have lymph node metastases. Their spread seems to be an orderly process. Other solid tumors (e.g., oat cell lung cancer and prostate cancer) often metastasize widely even when they are small. For such cancers, lymph node involvement is a reliable sign of metastases. Sarcomas seldom metastasize to the lymph nodes, but patients may develop distant metastases limited to the lungs alone. Remarkably, such patients sometimes are cured by resection of the distant lung lesions.

16. How else can solid tumors be treated with curative intent?

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Instead of surgical removal of the primary tumor and appropriate lymph nodes, the entire area may be treated with curative radiation. Some types of cancer are more responsive to radiation than others. The side effects of curative radiation treatment are formidable. Similar to those of surgery, they must be explained to the patient. When radiation kills cancer, it injures adjacent normal tissues. The damage to normal tissues continues over the course of the patient’s life. Although radiotherapists are getting better at directing their beams, the tolerance of nearby tissues to radiation remains the limiting factor in treatment of cancers with radiation alone.
KEY POINTS: WHAT IS CANCER?

1. A neoplasm is a new growth of tissue in which cells grow progressively under conditions that do not prompt the growth of normal cells.
2. Malignant tumors of epithelial cells are carcinomas.
3. Malignant tumors of mesenchymal cells are sarcomas.
4. About 25% of patients with solid tumors have detectable metastases at the time of diagnosis.
5. Tumor-infiltrating lymphocytes are lymphoid cells that infiltrate solid tumors and appear reactive to autologous tumor antigens.

17. What is adjuvant therapy?

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Adjuvant means “assisting or aiding,” but we use this term to mean assisting after surgical or radiotherapeutic control of the primary tumor. Adjuvant chemotherapy is of documented benefit in the treatment of breast cancer, colorectal cancer, stomach cancer, pancreatic cancer, and ovarian and testicular tumors. Adjuvant radiation therapy is effective in reducing the risk of tumor recurrence around the surgical site. It is often used in treating patients with rectal, breast, head and neck, and stomach cancers as well as sarcomas. Conceptually, both surgery and radiation are local/regional therapies. Although chemotherapy is obviously a systemic treatment, it may help sensitize tumors to radiation. The term “neoadjuvant” doesn’t really mean anything, but it is often used to describe preoperative chemotherapy or radiotherapy (which might more accurately be described as “induction” treatment).

18. What cancer treatments are available in addition to surgery, radiation therapy, and cytotoxic chemotherapy?

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Hormonal manipulation has been used for decades to slow the growth of some tumors. Stimulation of the patient’s immune system to combat cancer is potentially promising. This approach may involve vaccines, training of T cells, or enhancement of the immune response. New types of anticancer agents include drugs that interfere with tumor angiogenesis, antibodies and other drugs that interfere with growth factor receptors, other sorts of drugs that alter intracellular signaling, and drugs that restore cell cycle control. The limitation of all of these approaches resides in our inability to specify a target unique to cancer cells. Hence, treatments damage the rest of the patient, with potentially fatal toxicity.

19. Does the body fight cancer on its own?

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Certainly. Some scientists believe that early cancers are regularly extirpated by the immune system (as we “catch” cancer every day) and that clinical cancers reflect a breakdown in immune surveillance. Immunocompromised patients with transplants or AIDS develop cancers with frightening frequency. Thus, rejection and sepsis are no longer the most common causes of death among kidney transplant patients-it’s cancer. “Spontaneous remissions” of melanoma and renal cell carcinoma do occur and must be immunologically mediated. Indeed, these are the tumors that initially seemed to respond well to “adoptive immunotherapy” and interleukin-2.

20. What is a tumor-infiltrating lymphocyte (TIL)?

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TILs are lymphoid cells that infiltrate solid tumors and appear reactive to autologous tumor antigens. Compared with circulating lymphocytes, TILs more aggressively target cancer.

21. What are palliative treatments?

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Palliative means “affording relief but not curing.”

22. Give some examples of palliative procedures.

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Resection of the primary tumor in the face of distant metastases may be performed to treat bleeding or obstruction. Procedures to bypass intestinal or biliary obstruction in patients with unresectable cancer are common. Tracheotomies are created for patients who are unable to breathe because of upper airway obstruction, and feeding tubes may permit enteral nutrition in patients who cannot eat. Removal of isolated brain metastases often improves the patient’s quality of life. Many patients with functioning endocrine tumors benefit from reduction in tumor mass.

23. What is cytoreductive surgery?

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Cytoreductive (”debulking”) procedures are designed to decrease tumor burden. Simply reducing tumor bulk is seldom sufficient to prolong survival. For cytoreductive surgery to be beneficial, the nonsurgical (adjunctive) therapy must be highly effective-such as radiation for glioblastoma or chemotherapy for ovarian cancer.