A diagnostic strategy for identifying the primary origins of SMUP during the initial visit should be established with consideration of various characteristics of examination strategies. The types of examination strategies and their order in terms of efficacy should be determined based on the incidence of a specific type of cancer, extent of invasiveness, and time required for and ability and cost of the method.
In this study, lung cancer was most commonly associated with metastatic bone tumor, followed by malignant lymphoma; prostate, breast, and kidney cancer; and multiple myeloma. In patients with known or unknown primary origin at the time of bone metastasis diagnosis, the breast, lung, prostate, and kidney were the common primary origins[9, 10]. In patients with SMUP during the initial visit, the common primary origins were the lung, plasma cells, prostate, lymph nodes, kidney, breast, and liver[11, 12]. Whether cancer metastasizes at an early or late stage is based on the type of cancer. However, the lung, breast, prostate, and kidney were the frequent primary origins of skeletal metastases. Myeloma and lymphoma might not be included in the statistics, and hematological cancer was one of the most common primary origins.
The screening methods used differ based on the type of cancer. For lung cancer, low-grade helical CT scan is recommended[13, 14]. Mammography is used for the screening of breast cancer, and palpation is included in the diagnostic work-up examinations[15, 16]. Prostate cancer is usually assessed via blood test, including PSA with or without digital rectal examination[16, 17]. Paraprotein and sIL-2 R are important diagnostic markers for myeloma and malignant lymphoma, respectively[18, 19]. In this study, physical examination was useful for the diagnosis of breast cancer, and blood testing was effective for the detection of malignant lymphoma, prostate cancer, and multiple myeloma. Moreover, thoracoabdominal CT scan was effective for the diagnosis of different types of cancer, particularly lung, breast, and liver cancer. PET-CT scan and metastatic lesion biopsy were useful for the identification of most types of cancer. By contrast, the detection rate of chest radiography was <50% even in lung cancer. In screening for the primary origin of SMUP, thoracoabdominal CT scans were found to be effective particularly in the diagnosis of patients with lung, hepatocellular, renal cell, and pancreatic carcinomas. Moreover, an elevation serum AFP or PSA level is relatively specific to hepatocellular or prostate carcinoma[12].
Using our strategy modified based on a previous literature[8], physical examination, blood test, chest radiography, and thoracoabdominal CT scan were effective in identifying lesions in 41 (65%) of 63 patients with SMUP during the initial visit. In a previous report, in approximately 53.3% of patients, the primary origin of SMUP was diagnosed via common examinations, such as medical history taking, physical examinations, chest radiography, blood test, and whole-body CT scan[11]. The examinations included in the first half of the diagnostic strategy are less invasive and have fewer side effects and are useful for the diagnosis of common primary origins. For example, palpitation for breast cancer, blood test for prostate and hematological cancers, and CT scan for lung and breast cancers are extremely useful examinations. Meanwhile, the efficacy of chest radiography may be limited. However, it was effective in evaluating the patients’ general condition. Therefore, if CT scan could be performed quickly, radiography might be omitted from this strategy. PET-CT scan was found to be a useful method in identifying the primary origin of SMUP[20, 21]. In few cases, PET-CT scan was effective for diagnosis of advanced-stage gastric cancer, which is not detected on CT scan. Furthermore, the diagnostic ability of PET-CT scan (60.0%) was higher than that of CT scan (38.6%). However, CT scan was effective in detecting common primary cancers. That is, in more than 50% of cases, the primary origins of SMUP were identified during the initial visit via common examinations, including CT scan. In addition, PET-CT scan is more expensive and time-consuming than CT scan. The primary origin of an SMUP could be identified more quickly with the use of CT scan than PET-CT scan[22]. Moreover, CT scan might be more useful than PET-CT scan in detecting the primary origin of SMUP from a comprehensive perspective.
This study had several limitations. First, the number of patients in this study was relatively lower than that in other recent studies. Hence, a statistical analysis was not performed. However, we believe that the results were accurate even though only few patients were included. Next, data on the period from the initial visit to the diagnosis of the primary origin and prognosis of patients with SMUP were not included. The overall survival rate in patients with metastatic bone tumors was correlated with the presence of SRE and spinal metastases, performance status, number of metastases, and primary sites[11, 22]. Moreover, it is challenging to identify a study showing the period between the day of initial visit and date of diagnosis of the primary origin and the relationship between the period required for diagnosis and prognosis. Whether this strategy saves the period required for diagnosing the primary origin of SMUP and whether early diagnosis of the primary origin improves patient prognosis are of great concern. Hence, these issues should be addressed in the future.