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Technology Assessment on Genetic Testing or Molecular Pathology Testing of Cancers with Unknown Primary Site to Determine Origin

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Cancer is one of the leading causes of death in the United States. The National Cancer Institute (NCI) estimates 1,596,670 new cases of cancer, excluding melanomas, will be diagnosed in 2011. Over half a million deaths in 2011 were expected to be attributed to cancer.

Cancer begins when the normal processes of cell division and death get interrupted and cells in a part of the body begin to grow uncontrollably. The abnormal cells multiply and interrupt normal function of the tissue. Hanahan and Weinberg suggest that malignant growth is a result of a series of genetic changes in cells, which cause the following six essential modifications in cell physiology: self-sufficiency in growth signals, inaccuracy in growth-inhibitory (antigrowth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.

Cancers are most commonly classified by the primary site of occurrence, but they are also secondarily grouped by the type of cell that the cancer is formed from. In this classification, a carcinoma is a cancer that begins in the epithelial cells that line the inside or outside of an organ. The two most common forms of carcinomas are squamous cell carcinomas and adenocarcinomas. Squamous cell cancers are formed by flat cells that resemble cells normally found on the surface of the skin or the linings of the throat, esophagus, lungs, anus, cervix, vagina, etc.; adenocarcinomas are cancers that develop from gland cells. Most cancers in the stomach and intestines are adenocarcinomas. The four most commonly occurring cancers in the United States—prostate cancer in men, breast cancer in women, lung cancer, and colorectal cancer—are all carcinomas. Cancer that develops from cells of the immune system found in the lymph nodes and other organs are called lymphomas; melanomas develop from cells that produce the skin’s tan; sarcomas develop from connective tissue cells that are usually present in tendons, ligaments, muscle, fat, bones, cartilage, and related tissue; and germ cell tumors develop in the testes for men or ovaries for women or in the parts of the body where these organs developed in the fetus.

In most cases, cancer cells form solid tumors. The diagnostic work-up in a patient newly diagnosed with cancer usually includes an assessment of the stage of the cancer. Cancer staging is a way to describe the severity of the disease. It also determines the treatment modality. Most tumors can be classified as Stage 0, Stage I, Stage II, Stage III, or Stage IV. Increasing stage denotes increasing severity, with Stage IV indicating that the cancer has spread to distant organs or metastasized.

The choice of a treatment for cancer varies with both the site of primary origin and the type of cancer. Most common cancer treatments consist of combinations of three components: (1) surgery to remove as much of the cancerous tissue as possible, (2) radiation to kill or slow the growth of cancerous tissue that cannot be accessed safely through surgery, and (3) tissue-specific chemotherapy to kill cancer tissue through a system-wide administration of “anticancer” drugs. Chemotherapy is always a part of the regimen when a patient has metastatic cancer (i.e., their disease has spread from the primary organ to a distant organ). Patients who are diagnosed as having Stage III or Stage IV cancer usually have metastatic cancer. There are curative treatments for some metastatic cancers; if a curative treatment is not available, it is still possible to treat the metastatic cancer and slow the progression of the cancer to increase survival or relieve symptoms and improve quality of life.

As the understanding of the molecular functioning of cancer cells increases, targeted therapies designed to attack specific characteristics of a cancer cell are being added to treatment regimens. Drugs used in these regimens are targeted to attack specific functions of cancer cells and leave healthy cells alone. Cancer cell type and primary site both affect the efficacy of targeted therapies. In order to design the most effective treatment regimen for a patient with metastatic cancer, it is therefore important to know the site of the primary tumor or at least the cancer cell type.

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