Integrating the time factor into the definition of metastasis of unknown origin.

Patients with cancer of unknown primary site are common, representing 5%10% of all cancer patients (7). Combination chemotherapy, often used with surgery or radiation therapy, has proved to be potentially curative for several metastatic tumors of known primary site. Likewise, some patients with metastasis of unknown origin (MUO) also have responsive neoplasms and could be treated successfully (2,3). There is no doubt that, unless the primary tumor is promptly diagnosed and treated, most of these cases will have a rapid downhill course. Therefore, time is also an important factor in the workup and management of these patients. In infectious diseases, fever of unknown origin (FUO) is defined as an illness of more than 3 weeks' duration, documented fevers above 38.3 *C (101 *F) on several occasions, and the lack of a specific diagnosis after 1 week of inpatient investigation (4). This definition has been updated by Petersdorf (5) who suggested "One week of intelligent and intensive investigation, which, in most patients, could be conducted on an outpatient basis. However, a minimum temperature of 38.3 °C and 3 weeks of fever is necessary for the diagnosis of FUO." Most physicians send the patients with cancer of unknown primary site to the major referral centers with diagnostic and therapeutic facilities. Unlike the diagnostic procedures in infectious diseases, the work-up in oncology patients is somewhat more complicated and time consuming. We propose that the time factor should also be integrated into the definition of MUO. Accordingly, MUO may be defined as the presence of metastatic illness with an unknown primary site after 2 weeks of intensive investigation at a center with good diagnostic facilities. Those who deal with cancer should never forget that the elapsed time without diagnosis and delay in therapy may worsen the prognosis in these patients.