174P - Frequency and prognostic value of circulating tumor cells in cancer of unknown primary

Background

Cancer of unknown primary (CUP) is defined as a primary metastatic malignancy, where the primary tumor remains elusive in spite of a comprehensive diagnostic workup. Patients with CUP have a poor prognosis, making the need for the development of novel therapeutic and prognostic tools urgent. The frequency and prognostic value of circulating tumor cells (CTCs), which are considered to be the source of metastasis, has not yet been systematically evaluated in CUP.

Methods

92 patients with a confirmed diagnosis of CUP according to the ESMO guidelines, who presented to our clinic between 07/2021 and 03/2023 provided blood samples for CTC enumeration using CellSearch® methodology. CTC counts were correlated with demographic, clinical and molecular data generated by comprehensive genomic profiling of tumor tissue.

Results

CTCs were detected in 35% of all patients. The highest CTC frequency was observed among patients with unfavorable CUP (18/53, 34%), while patients with single-site/oligometastatic CUP harbored the lowest CTC frequency (4/28, 14%). Disease burden and the number of affected organs had no significant effect on the CTC detection rate (P=0.251 and P=0.805). CDKN2A alterations were slightly more common in CTC-negative patients (P=0.086). High CTC levels (5 CTCs/7.5 ml) predicted for adverse overall survival (OS) compared to negative or low counts (median 74 vs. 19 months; Log-rank P=0.002; HR 3.73; 95% CI 1.54-9.00). Progression-free survival was also affected by CTC status, the effect did not, however, reach statistical significance (median 7.4 vs 3.6 months, Log-rank P=0.1). CTC dynamics over the course of the disease were prognostic for OS, with patients that were either consistently CTC-negative or turned negative during treatment demonstrating the best prognosis.

Conclusions

The number of CTCs is a predictor of survival in patients with CUP. Measurement of CTCs provides a useful prognostic tool in the management of these patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

German Cancer Research Center.

Disclosure

A. Stenzinger: Financial Interests, Personal, Advisory Board: Aignostics, AstraZeneca, Janssen, Bayer, Seattle Genetics, Pfizer, MSD, Eli Lilly, Illumina, Thermo Fisher, Amgen; Financial Interests, Institutional, Advisory Board: BMS, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: Roche, Incyte; Financial Interests, Institutional, Research Grant: Bayer, Chugai, BMS, Incyte. K. Pantel: Financial Interests, Personal, Advisory Board: Menarini/Silicon Biosystems. All other authors have declared no conflicts of interest.