CUP syndrome is said to occur when metastasis (tumor colonization) of the organism has occurred and the primary tumor cannot be identified. Approximately two to five percent of cancer patients are affected by CUP syndrome, which in most cases has a lethal (i.e., fatal) course.
What is CUP syndrome?
Cancer of Unknown Primary (CUP) syndrome is the metastasis of the organism by daughter tumors (metastases) for which no tumor of origin can be located during diagnostic procedures. The majority of malignant (malignant) tumors develop metastases when tumor cells metastasize via the lymphatic system (lymphogenic metastasis) or the blood system (hematogenous metastasis). In lymphogenic metastasis, carcinoma cells enter the lymphatic system, infiltrate the tissue there with tumor cells, and form lymph node metastases. If, on the other hand, carcinoma cells penetrate the blood system via a destroyed vascular wall, they are carried by this system and can form distant metastases. If the initial site of this process cannot be identified, a CUP syndrome is present.
Causes
Several factors are thought to be behind a CUP syndrome. First, the primary tumor may be too small to be identified by conventional diagnostic techniques, which is attributed to faster division of metastatic cells combined with a higher potential for degeneration. On the other hand, the primary tumor may have already been decomposed by the organism after metastasis has occurred. A possible surgical removal (e.g., ablation of an intestinal polyp) must also be considered in a CUP syndrome. In the majority of cases of CUP syndrome (20 to 30 percent), metastasis originates from a lung carcinoma, and in about 15 to 25 percent, it originates from a pancreatic tumor (cancer of the pancreas). However, metastasis in CUP syndrome can also originate from tumors of other organs (liver, kidney, stomach, uterus, and others), although common cancers (colon, prostate, mammary gland) rarely cause CUP syndrome.
Symptoms, complaints, and signs
The complaints and symptoms of CUP syndrome can vary widely. They depend very much on the extent of metastasis and the exact primary tumor. A general prediction of the symptoms is therefore not possible. However, those affected suffer from the formation of metastases, which can usually form in regions of the body alone. This results in severe pain, nausea or vomiting. Coughing or severe headaches can also occur in CUP syndrome and have a negative impact on the patient’s quality of life. CUP syndrome always leads to premature death of the affected person and therefore to a significantly reduced life expectancy of the patient. As a rule, the patient suffers from severe movement restrictions and limitations in everyday life. Often, CUP syndrome is also associated with severe psychological symptoms, so that patients and their relatives also suffer from depression or other psychological upsets. Furthermore, CUP syndrome leads to a loss of consciousness or a comatose state. Since the syndrome itself cannot be treated causally, only symptomatic relief is provided. In most cases, only about twelve months remain for the affected person until a final death.
Diagnosis and course
Because CUP syndrome is present only when the primary tumor cannot be identified, localization of the initial focus assumes a special position. In addition to a physical examination, blood analysis (including for tumor markers), and saliva, stool, and urine examinations, the results of biopsy (removal and histologic analysis) of the metastatic tissue are most important in determining the presence of a CUP syndrome. Since metastases usually show the histological structure (fine tissue structure) of the initial tumor, conclusions about the primary tumor are possible here. Furthermore, the results are decisive with regard to the therapy of the CUP syndrome. In addition, imaging procedures (sonography, X-ray, MRI, CT) as well as endoscopic and nuclear medicine examination procedures are used for diagnosis. The course of a CUP syndrome depends on the underlying parent tumor, the degree of metastasis, and the general condition of the affected person.However, on average, life expectancy is expected to be 6-13 months, with only about 33 to 40 percent of those affected by CUP syndrome still alive after 12 months.
Complications
In most cases, CUP syndrome leads to the death of the patient. However, it cannot be predicted how much the life expectancy of the affected person will be reduced. The symptoms and complications also depend on the region and the type of tumor. Therefore, no universal statement is possible here either. The affected person generally feels ill and weak and suffers from fatigue. There is also severe pain, which can affect the entire body. Furthermore, there is nausea and vomiting and also headaches. The quality of life of the affected person is extremely limited and reduced by the CUP syndrome. In many cases, patients are dependent on a stay in the hospital and on the help of other people in their daily lives in order to still be able to do so for the most part. As a rule, the affected persons remain alive for another year. As a result of the symptoms, it is not uncommon for patients to suffer from psychological complaints and depression. The patient’s relatives may also suffer from these symptoms. Treatment of CUP syndrome is not possible in all cases. Here, the exact risks and chances depend on the cancer.
When should you go to the doctor?
In most cases, CUP syndrome is already detected during other examinations, so an additional diagnosis by a doctor is not necessary. If the metastases have already spread in the body, treatment is usually no longer possible, so only the symptoms of the tumor disease can be mitigated. Patients should then contact a doctor if they experience pain or other discomfort due to the tumor. This may include nausea or coughing. In many cases, the affected persons are dependent on an inpatient stay in a hospital and premature death occurs. Likewise, psychological treatment is often necessary, which can affect not only the sufferers but also their relatives. A psychologist can be consulted for this. The treatment of the symptoms depends strongly on the affected region and is carried out by a specialist. In most cases, the syndrome significantly reduces the patient’s life expectancy.
Treatment and therapy
In CUP syndrome, treatment approaches that are commonly used for cancer are usually recommended. These include surgical therapy, radiation therapy, hormone therapy, and chemotherapy. Therapeutic measures for CUP syndrome depend on the histologic findings of the biopsy, the degree of metastasis, the suspected primary tumor, and the general condition of the affected individual. If the metastasis is localized, surgical procedures and/or radiation therapy may be considered. If there are multiple metastases at different sites, chemotherapy is recommended in most cases. If the histologic findings point to a hormone-sensitive parent tumor, hormone therapy is used. If there is a strong suspicion of a primary tumor in the lung, colon, kidney or liver, tyrosine kinase inhibitors or antibodies may be used, although these so-called targeted molecular therapies are still being tested in scientific treatment studies in CUP syndrome. In addition, the symptoms accompanying the disease are always treated. If, for example, there is metastatic involvement of the bones, additional agents are used to strengthen the bones (bisphosphonates). If the metastasis is already very advanced or if the person affected by CUP syndrome has a poor constitutional condition, the therapeutic measures are aimed primarily at reducing symptoms, improving the quality of life, and preventing complications.
Outlook and prognosis
In most cases, CUP syndrome results in premature death of the patient. Because the tumor has already spread throughout the body and metastasis has occurred, the disease usually cannot be fully treated. Only the individual symptoms can be limited. Since the primary tumor cannot be identified in the process either, the prognosis in CUP syndrome is very poor. The treatment of the syndrome takes place with the help of various therapies.When chemotherapy is used, various side effects occur that can have a negative impact on the patient’s quality of life. Radiation therapy can also remove some tumors, but cannot completely cure the syndrome. The further course is thus very much dependent on the extent of the tumors and their position and for this reason cannot be universally predicted. If no treatment is given for CUP syndrome, the patient’s life expectancy will continue to be shortened enormously. Often, the syndrome also leads to severe psychological discomfort, which may also affect the patient’s relatives.
Prevention
CUP syndrome cannot be prevented by specific measures. However, in general, risk factors that may contribute to cancer should be avoided. These include an unhealthy lifestyle characterized by physical inactivity, an unbalanced diet, and excessive alcohol and/or nicotine consumption.
Follow-up
In CUP syndrome, medical follow-up depends on the individual patient’s health status. Often, follow-up is based on symptoms, as causative therapy is usually not possible. In case of causative treatment, a 3-month follow-up is performed in the first two years after recovery. Thereafter, six-monthly check-ups are performed, focusing on physical examinations. Psychological follow-up is not usually provided. After the fifth year, the examinations are discontinued, provided that no recurrences have been detected in the patient. In addition to medical follow-up, the patient himself must take some measures to ensure a full recovery. Above all, it is important to keep a diary of complaints in which all unusual signs of the disease and any side effects of the prescribed medication are noted. Although no major health problems should occur after completion of treatment, detailed documentation helps to identify any symptoms and thus also to diagnose recurrences promptly. Follow-up care may also include vocational rehabilitation and establishing new hobbies and friendships. If the patient is receiving palliative care, therapeutic measures must be taken to work through the fears and concerns associated with the diagnosis. Talk therapy can relieve the psyche and thereby also increase the patient’s quality of life.
What you can do yourself
The diagnosis of CUP syndrome brings challenges for the patient’s usual everyday life and his or her own psyche. First, affected persons make out with their environment, last with themselves. The environment includes relatives and friends. Together with them, it must be clarified to what extent they will help with necessary care at home. There is also the question of how accessible the sanitary facilities at home are. Aids such as walking aids must be purchased and must be usable in the home. Financial aspects in particular need to be considered. Any additional payments can be a burden. Supplementing ambulatory care services can be taken up, if familiar care achievements can furnish only partly or not at all. Self-reflection is often the most difficult part. Patients themselves know exactly what is important to them. Close relatives can be as much a help as a burden. It should be noted: the psychological impact of a diagnosis of CUP syndrome is comparatively great because doctors do not find a known primary tumor. The accompanying despair can be discussed in self-help groups. Some patients deal with feelings such as fear by working creatively. Pictures or sculptures, as well as literary texts, allow the situation to be processed. It is also advisable to consult psychosocial cancer counseling centers. They can be found in many German cities. They work free of charge or for a small fee.
