Cancer of Unknown Primary Site

This open label, non-randomized, multi-center, pragmatic study aims to establish whether patients with rare tumors can benefit from matched molecular therapy as dictated by their next-generation sequencing (NGS) results.

This study aims to evaluate the diagnostic efficacy, therapeutic assessment, prognostic analysis, and impact on clinical treatment decisions of 18F-FAPI PET/CT in patients with cancer of unknown primary.

The goal of this clinical trial is to improve diagnosis and treatment strategies for patients with Cancer of Unknown Primary (CUP) by using advanced molecular profiling to identify the likely tumor origin and guide therapy. The main questions it aims to answer are: Can comprehensive molecular profiling help determine the origin of CUP tumors? Does identifying the tumor origin improve treatment choices and survival outcomes compared to historical data? Participants will: * Undergo a new biopsy to collect tumor tissue for advanced analyses. * Provide blood samples for circulating tumor DNA (cfDNA/ctDNA) analyses. * Provide a fecal sample for microbiome analysis. * Have their tumor tissue analyzed using: Methylation profiling and comprehensive gene panel testing. * Have the results reviewed in a specialized CUP molecular MDT meeting to determine the likely tumor origin and guide treatment. * Have their tumor tissue samples biobanked for further exploratory whole genome sequencing (WGS) and RNA sequencing.