VII.

Treatment

The traditional means of treating cancer have been surgery, radiation, and chemotherapy. However, revolutionary treatments are now under development and researchers are using laboratory discoveries to design drugs that will exploit specific biological processes in cancer.

A.

Surgery

The principal approach to curing cancer is to remove all the malignant cells by a surgical operation. In the past this meant the removal of all of the involved tissue and as much potentially involved tissue as possible, including adjacent tissues and lymph nodes. For some tumours, notably cancer of the breast, this radical degree of surgery (see mastectomy) is not always necessary.

Refinements in surgical techniques, improved knowledge of physiology, advances in anaesthesia, ready availability of blood products, and potent antibiotics have permitted less extensive surgery with more rapid recovery and less resulting disability. Many cancers, though, are at too advanced a stage at the time of diagnosis to be eradicated by surgery. If local extension involves neighbouring tissues that cannot be sacrificed, or if distant metastases are already present, surgery will not cure the cancer. Even when it is clear that surgical cure is not possible, however, surgery may help to relieve symptoms, such as obstruction, or to reduce the size of the tumour in an effort to improve the patient’s response to subsequent radiotherapy or chemotherapy.

B.

Radiation Therapy

Ionizing radiation, which may be either electromagnetic or particulate, is destructive to tissue. Electromagnetic radiation includes gamma rays, which are emitted by radioactive decay, and X-rays, which are produced when a beam of electrons strikes a heavy-metal target. Particulate radiation includes beams of electrons, protons, neutrons, alpha particles (helium nuclei), and negative pi mesons (pions).

Tumours vary greatly in their sensitivity to radiation. A “sensitive” tumour is one that is more sensitive than surrounding normal tissues. When such a tumour is readily accessible—a superficial tumour, for example, or one in an organ like the uterus, into which a radiation source can be introduced—it may be curable by radiation therapy. Because of its relatively sparing effect on normal tissues, radiation is useful when a tumour cannot be removed because surgery would damage vital adjacent tissue, or because it has begun to infiltrate adjacent structures that cannot be sacrificed. Radiation therapy is also extremely useful for palliation (temporary relief), especially of metastatic tumours.

Radiation can also be a valuable adjunct to surgery. Pre-operative radiation may rapidly sterilize the tumour cells and prevent them from seeding at surgery. It may also shrink the tumour and make surgery easier, or shrink an inoperable tumour so that it becomes operable. In other tumours, post-operative radiation is used.

A major risk of radiation therapy, however, is that the application of high doses to a cancerous organ can damage adjacent organs where there are no tumour cells. In 2001 doctors in Italy treated a cancer by removing an entire organ (a liver), administering radiotherapy, and then re-implanting the organ back into the body. Although a year later the liver was still functioning normally, the procedure is many years away from becoming a widely available option.

C.

Chemotherapy

Chemotherapy is the use of drugs in the treatment of cancer. Since a drug is distributed throughout the body by the bloodstream, chemotherapy is prescribed for tumours that have spread beyond the area accessible by surgery or radiotherapy. A number of different types of anti-cancer drugs are used, but nearly all work by interfering with DNA synthesis or function. Rapidly dividing cells are therefore more sensitive to chemotherapy.

C.1.

Cell Sensitivity

Cancers have a larger proportion of dividing cells than do normal tissues, in which stem, or replenishing, cells are dormant. This means that normal cells are more resistant to drug effect than the cancer cells, which proliferate rapidly. The most rapidly proliferating normal cells are in the bone marrow and the lining of the gastrointestinal tract. These are the most sensitive normal areas likely to be affected by chemotherapy and therefore constitute the sites of toxicity that will limit the tolerable dose of most drugs.

Therefore, to be effectively treated, a tumour must have a sensitivity greater than that of the most sensitive normal tissue. Some tumours may be many times more sensitive, but many are only slightly more sensitive. Fortunately, the normal bone marrow cells can divide faster than malignant cells and thus recover more rapidly. This permits a repeat cycle of the drug before the tumour has regrown to any great extent. Repeated cycles can steadily deplete a tumour before resistance occurs.

Some tumours are so sensitive to chemotherapy that a chemotherapeutic cure is possible in a high percentage: uterine cancer; acute lymphoblastic leukaemia, especially in children; Hodgkin’s disease; testicular carcinoma; and several childhood cancers are examples. These cancers have often already spread at the time of diagnosis and cannot be treated by other means. However, other advanced cancers respond well to chemotherapy and can be controlled for a long time, so chemotherapy is commonly used for palliation.

C.2.

Toxicity and Resistance

The two major problems limiting the usefulness of chemotherapy are toxicity and resistance. Techniques that avoid or control toxicity and reduce the risk of resistance have steadily improved. It is important to begin treatment as early as possible, to use the optimal dose of the drug, and to repeat cycles as quickly as possible, while giving the patient a chance to recover somewhat from toxicity.

The use of multiple drugs is effective. Combination chemotherapy employs several drugs (often three to six at a time), each of which is effective as a single agent. The drugs used have different mechanisms of action, making cross-resistance less likely, and different types of toxicity, so that each may be given at optimal dose without causing fatal additive toxicity.

C.3.

Chemotherapy with Other Treatments

High doses of chemotherapy can be given if a bone marrow transplant or bone marrow or stem cell rescue is part of the treatment regime. This is most often used in leukaemia treatment, but there are trials under way in other cancers.

Chemotherapy may also be used with surgery or radiation as combined modality therapy. It is often used as an adjuvant, or helper, when surgery is the primary therapy. As such it is usually given after surgery. This type of therapy has greatly increased the cure rate of breast cancer. The major purpose of chemotherapy as an adjuvant is to kill off micrometastases that may have been established before surgery.

Recently, chemotherapy has been used before surgery as a neo-adjuvant. This therapy has the same effect as adjuvant chemotherapy but may also shrink a tumour, making it more easily operable.

D.

Hormone Therapy

Many cancers arising from tissues that are hormone-dependent, such as the breast, prostate, endometrium (uterine lining), and thyroid, are responsive to hormone manipulation. This may consist of removing the source of the stimulating hormone or the administration of various hormones, antihormones, and hormone blockers, such as tamoxifen.

E.

Other Approaches

Several promising new approaches to the treatment of cancer are being taken. In one, biological agents known as biological response modifiers are used to modify the response of the body (particularly the immune system) to cancer. Another approach involves biological agents that stimulate certain cells, which can then attack the malignant cells. The best example is the use of interleukin-2 to stimulate the patient’s lymphokine-activated killer lymphocytes (LAK cells).

Research is also concerned with tumour-specific antigens, against which antibodies could be raised. These anti-tumour antibodies would be used to treat cancer either directly or by coupling to a chemotherapeutic agent. The antibody could identify the malignant cell and stick to it, thus delivering the drug directly to the target.

For example, a new drug under development blocks the enzyme that destroys the connective material between cells, which furthers the spread of the cancer. The drug thereby prevents cancer cells breaking away from the tumour and spreading to other parts of the body.

F.

Other New Approaches

Another growing area of research is gene therapy. This employs various methods to introduce genetic material into the cancer to make it more recognizable to the immune system. It can also make the cancer cells more sensitive to drug treatments, or it can place new genes into T-cells to make them more active. Specific types of human cells, such as breast and prostate cells, could be genetically modifed to determine which particular genetic changes cause cancer. Such knowledge could then be used to identify people at increased risk for certain cancers. Specialized drugs could be produced that will target specific genetic flaws linked to cancer.

Work is also under way to develop vaccines by removing cells from the patient and modifying them in the laboratory so that they secrete a protein that stimulates the immune system. The cells are irradiated to stop them dividing, and are then injected into the patient.

Even if cured, a cancer patient may be left with serious disabilities. Every effort must be made to achieve the maximum possible quality of life through rehabilitative techniques, including reconstructive surgery. For the patient who is not cured, palliative therapy may achieve comfort and good function for months or years. Pain can be a severe problem, as can depression, but both can be relieved today much more than in the past.