indiacancer.org - Carcinoma of Unknown Primary

Carcinoma Of Unknown Primary (CUP)

		What is Carcinoma Of Unknown Primary?
		How does CUP present?
		How is CUP detected?
		How is CUP treated?
		What are the side effects of treatment for CUP?
		What is the importance of follow up?

What is Carcinoma Of Unknown Primary?

When the site of the original cancer is unknown, but there is a detectable evidence of spread of a cancer, then the condition is known as carcinoma of unknown primary. This happens occasionally, in 2 - 4% of patients.

In reality, CUP is better defined or described by the places of metastasis.

How does CUP present?

	The possibilities as far as the presentation of CUP is concerned, are endless. The following is the most common way:
		A swollen lymph node(s) in the neck, armpit, groin, chest, or abdomen. (Lymph nodes are small bean-shaped structures, which act as stations for drainage of lymph, a clear watery fluid, which courses through out the body in transparent, thin tubes called lymph channels or lymphatics, from various organs).

How is CUP detected?

Besides performing a detailed examination after taking a detailed history, the doctor may order some specific investigations- A biopsy is the most important investigation as far as CUP is concerned, since it may give some clue as to the origin of the disease. A biopsy is the removal of a small piece of tissue to be sent for histopathological examination under the microscope in order to establish diagnosis of the tissue of origin.

Several imaging investigations may have to be performed as well, such as USG, CT, and MRI.

CUP is commonly found to originate from the lungs or pancreas, or less commonly, from the breast, rectum or prostate. So the focus of your clinician may be on these organ systems.

A triple'scopy is an investigation in which three forms of endoscopy are done in the same sitting on an outpatient basis.

Endoscopy is a procedure in which hollow tubes in various parts of the body are inspected directly by introducing self-illuminated, fiberoptic or stainless steel telescoping instruments called endoscopes.

The three different types of scopes which are used in triplescopy, are the direct laryngoscope, which is used to visualize the larynx or the voice box; bronchoscope, which is used to visualize the trachea and the bronchi which are the air pipe and its divisions, and esophagoscope, which is used to visualize the esophagus, which is the food pipe.

A posterior rhinoscopy may also be included in this investigation, which is inspection of the posterior wall and the roof of the nasopharynx (the top of the throat) and nose.

How is CUP treated?

Treatment options depend on where the cancer is found and what it looks like. You can group them into several categories:
	CUP found in the cervical lymph nodes.
	Poorly-differentiated carcinomas.
	Metastatic melanoma to a single nodal site. (For description of melanoma please see the page on melanoma).
	Isolated axillary metastasis (cancer that has spread to the nodes in the area of the armpit).
	Multiple involvement (Several areas have been involved).
	Inguinal nodal metastasis, where the cancer has spread to the nodes in the groin area.
The bastions of treatment are surgery, radiation, chemotherapy, and hormonal therapy. Surgery is still one of the most routine methods of treatment for CUP. The metastatic disease is removed along with a certain margin of healthy tissue around it. If there is spread to the lymph nodes in the neck, then a procedure called a radical neck dissection is done in which the lymph nodes and fibrofatty tissues and muscles along with the internal jugular vein, which is one of the main veins of the neck, are removed, leaving behind vital structures only. Nodes in the groin, if positive, are treated with a superficial groin dissection. If it has spread to the tissues surrounding the nodes in the groin, then the doctor may also have to do a block resection of the tissues involved. The alternative local therapy to surgery is radiation therapy. This involves the use of high energy, penetrative rays to destroy cancer cells. It affects cancer cells only in the zone treated. Radiation therapy is also employed for palliation i.e. control of symptoms alone in an advanced cancer. Radiation therapy can also be used in adjunct to surgery or chemotherapy, either before or after. Teletherapy or external radiation is given via a machine remote from the body while brachytherapy or internal radiation is given by implanting a radioactive source within the involved tissues. Patients may or may not require both modalities of radiation. Radiotherapy, after initial planning, usually takes just 5 to 10 minutes per day, 5 days a week for about 6 weeks. This time period is flexible depending upon the modality of radiation used. Besides local therapy, the best attempt to control cancer cells circulating in the body and lodged at places other than the unknown focus is by using systemic therapy (therapy which affects the entire systems of the body) which is in the form of injections or oral drugs. This form of treatment is called chemotherapy. This form of treatment is given in a cyclical manner (each set of drugs is repeated usually after every 3-4 weeks). Chemotherapy can also be used in combination with surgery, radiotherapy or both, either before or after. Hormonal therapy is a form of systemic therapy, which aims at cutting of the supply of hormones to the cancerous cells, in order to prevent their further propagation and replication. For newly diagnosed carcinomas of unknown primaries, the following protocols may be followed:
	If the cancer is found in the cervical or the neck lymph nodes, then one of the following options may be exercised:
		Surgery to remove the tonsils, which is a tonsillectomy.
		Radiation to the entire field.
		Primary radiation followed by surgery.
		Radical neck dissection as described above.
		Radical neck dissection followed by radiation therapy.
		If its a poorly-differentiated carcinoma (which is a very aggressive variant of carcinomas in which cells take on a fetal pattern) is noticed, then the treatment is usually multidrug chemotherapy.
Surgery or radiation have also been used for patients with neuroendocrine tumors, which have metastasized as poorly-differentiated forms. (Neuroendocrine tumors are those, which arise from the nervous system and the hormonal system or the endocrine system of the body.) If there is adenocarcinomatosis in the peritoneum, which is the sac in the abdomen which contains most of the organs, then the treatment is usually chemotherapy using multiple drugs. Metastasis to the armpit lymph nodes or the axillary lymph nodes usually arise from the breast or the lung. Special investigations including a mammography, which is a special x-ray for the breast, may be performed to locate undetected primary foci in the breast. If the mammography does reveal focus in the breast, then a mastectomy, which is a surgery to remove the breast along with an axillary dissection to remove the lymph nodes and fibrofatty tissue in the axilla, is performed. To this is added chemotherapy for breast cancer. In case no live focus is found in the breast, then just surgery to remove the lymph nodes is performed. If cancer is found in the inguinal or the groin nodes, then one of the following options may be entertained:
	Surgery to remove the cancer.
	Superficial groin dissection to remove the lymph nodes in the groin.
	Chemotherapy may become an add-on if some evidence is found of the type of cancer.
If the disease is a melanoma, which is a carcinoma arising from the pigment cells of the body, and it is present in a single nodal site, then the treatment would be surgery to remove the offending lymph nodes. If multiple sites are showing cancers without the primary being known then the therapy has to be systemic, either hormonal therapy for prostate cancer or chemotherapy and hormone therapy for breast cancer or chemotherapy for ovarian cancer. The best treatment is never known if the source of cancer is never detected. Recurrent CUP The treatment depends on what was the treatment given before and in which part of the body it has come back and what was the original etiology or the causative cancer.

What are the side effects of treatment for CUP?

	Unfortunately treatment for cancer does cause damage to the healthy tissues. Please ask the clinician about any possible side effects before any form of treatment commences. The effects of radiation depend upon the dose of radiation, the size of the area radiated, and the number and size of each fraction. The commonest side effect is extreme fatigue. Although bed rest is good, most radiotherapists advise the patient to be as mobile as possible. Another common problem is that of radiation dermatitis in which the skin covering the radiated area becomes red, dry, itchy, and may show signs of scaling off. This will slowly settle down after radiation ceases, but there may be a permanent 'bronzing' of the skin. It is important to note here that this skin problem is associated only with teletherapy or external radiation therapy. Radiation also may cause nausea and vomiting, diarrhea, urinary discomfort. There may also be a fall in the white blood cells, which are needed by humans to fight infection. Usually the radiotherapist can suggest the drugs and diet necessary to alleviate such problems. The various drugs in chemotherapy cause a varied spectrum of side effects. The severity and variability of these symptoms are very individualistic, changing from patient to patient. Some of the common side effects are:
		Skin rashes.
		Loss of hair.
		Diarrhea.
		Vomiting.
		Tingling and numbness in the fingers and toes.
		Hearing loss.
	Most are temporary and recede after therapy is over. Hair growth gradually starts after cessation of chemotherapy. The medical oncologist will usually be able to reduce the severity and spectrum of these side effects. The psychology of the patient is very important during therapy. Better psychologically prepared the patient is, better are his chances of having decreased side effects. The patient should drink large quantities of water while the therapy is in progress, and preferably avoid uncooked or raw food. Water should be filtered or boiled. Any relative or person who has any sort of infection such as common cold should be asked to desist from coming close to the patient.

What is the importance of follow up?

The importance of followup cannot be overemphasized. It is a fatal fallacy to assume on the patient's part that once the primary or the first phase of treatment is over, then he or she is cured. It must be stressed here that cancer has a notorious proclivity of coming back again and again. The only way to fight this is to pick up any problem when it is still early, so that it can be nipped in the bud. And the only way to do this is to follow up when the doctor calls you for the next visit. Each such visit will include a detailed history, a physical examination (including an internal i.e. a rectal or vaginal examination), a chest x-ray, an ultrasonography or a CT scan, and various other blood studies as indicated.