Diagnostic Approach to Bone Metastasis of Unknown Origin: a Systematic Review

BACKGROUND Among all MBD cases, 3% have an unidentified origin and are commonly misdiagnosed. On average, nearly 75% of MBD cases with an unknown origin take four months to diagnose. This difficulty in identifying the primary cancer limits the treatment of skeletal metastases to palliative measures, negatively impacting a patient's prognosis. The purpose of this systematic review is to evaluate the current diagnostic work-up approaches available for MBD. METHODS This systematic review was carried out according to the guidelines of the (PRISMA) 2020 Statement, including studies with a population of interest of MBD with unknown primary origin. We excluded studies with non-English language and MBD cases with known origin. The intervention of the diagnostic approach was the primary outcome. The authors searched three electronic medical databases. Individual reviewers performed quality and risk of bias assessments. RESULTS All ten articles were cohort studies, with the median age of the subjects ranging from 55.6 to 65.2 years. The most frequently recommended supporting examination was biopsy, with a detection rate of 38.2%, followed by chest X-ray and CT scan, both with a detection rate of 26.7%. Overall, the detection rate of the primary lesion from individual examinations ranged from 2.8% to 38.2%, highlighting the difficulty of diagnosis when relying solely on a single examination. CONCLUSIONS Biopsy is crucial in identifying the primary lesion of metastatic bone disease with an unknown origin, with a detection rate of 38.2%, making it the most frequently recommended examination. However, this review has several limitations. A few assumptions were made in the synthesis of numerical data.