Effect of national multidisciplinary tumor boards on diagnostic stratification and therapeutic management in cancers of unknown primary.

e13666 Background: With the increasing complexity of current diagnostic investigations, the integration of clinical, pathological and genomic characteristics is crucial for the management of patients (pts) with cancers of unknown primary (CUP). A national multidisciplinary tumor board (NatCUPMTB) was created in July 2020 in France to discuss the diagnostic and therapeutic management of CUP pts. The objective of this study was to evaluate the diagnostic, prognostic and therapeutic impact of NatCUPMTB after 30 months of activity. Methods: This was a multicenter retrospective study with prospective follow-up. All pts discussed at least once in the NatCUPMTB between July 2020 and January 2023 were included. Pts and tumors characteristics, pathological and genomic analyses including WGS, WES and RNAseq performed on the two PFGM2025 (French Genomic Medecine Plan 2025) national large-scale sequencing platforms, NatCUPMTB conclusions, and follow-up were collected. Results: 151 pts were included. The median age at diagnosis was 58 yo, 55% were female, and the median number of metastatic sites at diagnosis was 2. The median time between diagnosis and first MTB presentation was 4 months (1-20). At the time of analysis, NatCUPMTB conclusions and long-term follow up were available for 92 pts. MTB investigations enabled to identify a likely primary origin in 53/92 (58%) pts, the most frequent being renal carcinoma (N=9) cholangiocarcinoma (N=6) and lung carcinoma (N=6). For 16/53 (30%) pts, MTB diagnoses were based on the combination of clinical, pathological and genomic investigations. NatCUPMTB recommended a personalized therapeutic strategy in 54/92 patients (59%). After a median follow-up of 11.2 months, the median overall survival (OS) was 17.4 months from diagnosis and 10.1 months from the 1 st MTB presentation. Pts for which the MTB had a diagnostic impact had increased OS from 1 st MTB presentation compared to pts with no diagnostic orientation (14.5 vs 4.4 months, p=0.0007). Moreover, pts having received a treatment following MTB recommendation (based on likely origin or targetable alteration) had increased OS from 1 st MTB presentation compared to pts having received other treatments (14.5 vs 4.4 months, p=0.003). Conclusions: NatCUPMTB provides significant diagnostic and therapeutic benefit in pts with CUP. Early presentation of pts at NatCUPMTB as soon as CUP diagnosis is suspected should be recommended.