The CUP syndrome (carcinoma unknown primary).

Summary o 1. Ten per cent of adenocarcinomas present without a detectable primary. Cancer unknown primary is a clinical state in which a metastatic deposit is more apparent than its primary. 2. Cancers without a known primary may develop because o (a) metastases may occur during a prolonged clinically silent period of a neoplasm, (b) the primary neoplasm may be small or undergo actual regression, or (c) the primary may exhibit an unusual pattern of progression resulting in early dissemination. 3. Cancers of unknown primary exhibit atypical behavior. o (a) CUP primaries often originate in organs other than the expected pattern of known primaries and originate below the diaphragm 75% of the time. The most common source is pancreas, followed by cancer of the liver and stomach. (b) Twenty-five per cent of CUP cancers originate above the diaphragm. The most common sources in this location are cancers of lung and thyroid. Breast cancer is a rare cause of cancer unknown primary. 4. Cancers of unknown primary metastasize in a pattern other than that of known primaries from the same organs. 5. The philosophy of management of CUP cancers should reflect the recognition that tumors that present with metastases are incurable and that a prolonged effort devoted toward diagnosis may detract from the quality of life. Therefore, a plan of diagnostic efficiency is essential. Careful physical examination, simple bedside and laboratory investigations supplemented selectively with studies of those organs found to be abnormal by these inexpensive screening procedures is appropriate. 6. Effective palliation and, at times, prolongation and survival are achieved with aggressive treatment of breast cancer, ovarian cancer, cancer of the prostate and possibly cancer of thyroid and gastric origin. Identification of these particular neoplasms may be of particular value. 7. Initial treatment should be directed at palliation of complications of the metastases which may include pain, respiratory distress, spinal cord compression and superior vena cava syndrome. 8. If the primary is found treatment should consist of that appropriate for the particular neoplasm. To date, there is no evidence that such cancers which present with metastases are as responsive to chemotherapy, or other modalities of treatment, as are those cancers that present in a more standard manner. 9. If the primary is not found it can be treated with combination chemotherapy which should include Adriamycin, as well as conceivably 5-fluorouracil and/or Mitomycin-C. Most early studies used 5-fluorouracil as a predominating agent. However, recent investigations suggest that more aggressive treatment may increase the response rate and quality and provide more effective palliation and a more durable life. This remains to be confirmed. 10. If available, patients with carcinoma unknown primary should be entered in prospective clinical trials in an effort to determine more effective treatments for this disease. This may depend on the knowledge of predominating metastatic sites, as well as the status of hormonal receptors. 11. Recognition of the atypical features of cancer unknown primary and its consideration as a syndrome may permit earlier palliation of symptoms, shorter hospitalization and an improved quality of life for these patients who require multidisciplinary and comforting support.