# Management and survival of patients with cancer of unknown primary discussed by a French national multidisciplinary tumour board: a retrospective analysis

## TL;DR

A French national tumor board improved cancer care and survival for patients with unknown primary tumors by using molecular data to guide treatment decisions.

## Contribution

Demonstrates the feasibility and survival benefit of multidisciplinary tumor board-guided molecular treatments for cancers of unknown primary in real-world clinical practice.

## Key findings

- Molecular profiling identified a putative tissue of origin in 70% of patients.
- Patients receiving MTB-oriented treatment had significantly better survival (18.6 months) compared to empiric treatment (11.0 months).
- 61% of patients received treatment based on MTB recommendations, with 74.5% following those recommendations closely.

## Abstract

Recent clinical trials have shown that molecularly-guided treatments can improve survival in patients with cancers of unknown primary (CUP). However, the feasibility and clinical benefit of these treatments for CUP in a real-life setting remain uncertain. In France, a national multidisciplinary tumour board dedicated to patients with CUP (CUP MTB) was created in 2020, with the aims of coordinating pathological and molecular diagnostic analyses and providing a centralised expertise for therapeutic orientation. This study aimed at evaluating the diagnostic and therapeutic impact of the CUP MTB on patients with CUP in a national real-life setting.

Patient and tumour characteristics, treatments and outcomes are collected prospectively. This study reports the diagnostic and therapeutic impact of all patients discussed in CUP_MTB between July 2020 and December 2023. The diagnostic impact was defined as the identification of a putative tissue of origin, and the initiation of a MTB–oriented treatment. Overall survival was estimated using the Kaplan–Meier method, and hazard ratios were calculated using Cox proportional hazard models.

A total of 246 CUP patients were referred to CUP_MTB (124 females and 122 men); 187 (76%) underwent pathological and molecular characterizations as recommended by the MTB. Tumour profiling enabled the identification of a putative tissue of origin (TOO) in 130/187 (70%) patients. The most frequent TOO were gastrointestinal (n = 29; 22%), lung (n = 22; 17%), breast (n = 21; 16%), and kidney (n = 19; 15%). 149 (61%) patients received a treatment based on MTB recommendation. 111/149 (74.5%) patients received MTB-oriented treatment, including systemic treatment oriented towards the putative TOO (n = 95, 63.8%), or treatment directed towards a targetable molecular alteration (n = 16, 10.7%). 38 (25.5%) patients for whom no MTB-oriented treatment could be recommended were treated with empiric treatment according to international guidelines. The median overall survival of patients treated with MTB-oriented treatment was 18.6 (IQR = 12.0) months, compared to 11.0 (IQR = 10.5) months in patients with empiric treatment (HR = 0.61, 95% CI 0.38–0.98, p = 0.04).

Integration of clinical, pathological and molecular data within an expert MTB is feasible in a real-life setting, enables access to molecularly guided treatments and improves survival for a large proportion of CUP patients. Our findings highlight the benefits of dedicated MTB and reference centres to improve the management of CUP.

10.13039/501100010463Institut Curie and the 2025 French Genomic Medicine Initiative.