PT - JOURNAL ARTICLE AU - Sivakumaran, Tharani AU - Cardin, Anthony AU - Callahan, Jason AU - Wong, Hui-li AU - Tothill, Richard W. AU - Hicks, Rodney J. AU - Mileshkin, Linda R. TI - Evaluating the Utility of <sup>18</sup>F-FDG PET/CT in Cancer of Unknown Primary AID - 10.2967/jnumed.123.267274 DP - 2024 Oct 01 TA - Journal of Nuclear Medicine PG - 1557--1563 VI - 65 IP - 10 4099 - http://jnm.snmjournals.org/content/65/10/1557.short 4100 - http://jnm.snmjournals.org/content/65/10/1557.full SO - J Nucl Med2024 Oct 01; 65 AB - Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumors for which standardized diagnostic work-up fails to identify the primary site. We aimed to describe the Peter MacCallum Cancer Centre experience with 18F-FDG PET/CT in extracervical CUP with respect to detection of a primary site and its impact on management. A secondary aim was to compare overall survival (OS) in patients with and without a detected primary site. Methods: CUP patients treated between 2014 and 2020 were identified from medical oncology clinics and 18F-FDG PET/CT records. Information collated from electronic medical records included the suspected primary site and treatment details before and after 18F-FDG PET/CT. Clinicopathologic details and genomic analysis were used to determine the clinically suspected primary site and compared against 2 independent masked reads of 18F-FDG PET/CT images by nuclear medicine specialists to determine sensitivity, specificity, accuracy, and the rate of detection of the primary site. Results: We identified 147 patients, 65% of whom had undergone molecular profiling. The median age at diagnosis was 61 y (range, 20–84 y), and the median follow-up time was 74 mo (range, 26–83 mo). Eighty-two percent were classified as having an unfavorable CUP subtype as per international guidelines.18F-FDG PET/CT demonstrated a primary site detection rate of 41%, resulted in a change in management in 22%, and identified previously occult disease sites in 37%. Median OS was 16.8 mo for all patients and 104.7 and 12.1 mo for favorable and unfavorable CUP subtypes, respectively (P &lt; 0.0001). Median OS in CUP patients when using 18F-FDG PET/CT, clinicopathologic, and genomic information was 19.8 and 8.5 mo when a primary site was detected and not detected, respectively (P = 0.016). Multivariable analysis of survival adjusted for age and sex remained significant for identification of a potential primary site (P &lt; 0.001), a favorable CUP (P &lt; 0.001), and an Eastern Cooperative Oncology Group status of 1 or less (P &lt; 0.001). Conclusion: 18F-FDG PET/CT plays a complementary role in CUP diagnostic work-up and was able to determine the likely primary site in 41% of cases. OS is improved with primary site identification, demonstrating the value of access to diagnostic 18F-FDG PET/CT for CUP patients.