Unfavorable carcinoma of unknown primary with a gastrointestinal profile: a retrospective study

• Published in: ESMO open Vol. 9; no. 8; p. 103662
• Main Authors: Guidi, L., Valenza, C., Battaiotto, E., Trapani, D., Ghioni, M.C., Crimini, E., Boscolo Bielo, L., Venetis, K., Belli, C., Bottiglieri, L., Gervaso, L., Cella, C.A., Ciardiello, D., Spada, F., Benini, L., Adorisio, R., Mane, E., Fazio, N., Guerini Rocco, E., Curigliano, G., Zampino, M.G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2024; Elsevier
• Subjects: biomarkers; carcinoma of unknown primary; gastrointestinal profile; Original Research; unfavorable CUPs; unfavorable CUPs; carcinoma of unknown primary; gastrointestinal profile; biomarkers
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2024.103662

Carcinoma of unknown primary (CUP) with a gastrointestinal profile is categorized by the European Society of Medical Oncology (ESMO) guidelines into favorable and unfavorable subsets. Favorable CUPs benefit from site-specific chemotherapy (CT), while the optimal treatment for unfavorable CUPs is still undefined.
We conducted a single-center retrospective study to describe outcomes of patients with CUP with a gastrointestinal profile referred to our center from January 2000 to August 2023. Favorable CUPs were defined as CK7−/CK20+/CDX2+ by immunohistochemistry, according to the ESMO definition; all other cases were considered unfavorable. The main endpoint was the progression-free survival (PFS) of first-line CT for advanced disease in all patients and in the unfavorable group.
A total of 56 patients were included, of whom 46 (82%) had unfavorable CUPs. After a median follow-up of 43.9 months, the median overall survival (mOS) was 11.8 months [95% confidence interval (CI) 8.3-15.3 months]. At univariate analysis, the presence of peritoneal metastases and residual tumor after primary surgery were associated with a shorter OS. The median PFS (mPFS) was 6.1 months (95% CI 3.6-8.7 months). In the unfavorable CUP subgroup, the mOS was 12.6 months (95% CI 8.7-16.5 months), the mPFS was 6.1 months (95% CI 3.5-8.9 months) and none of the CT regimens used showed to portend better PFS. The most relevant altered genes included: KRAS (9/29; 31%), BRAF (1/26; 4%), NRAS (1/25; 4%), TP53 (9/23; 39%).
CUPs with a gastrointestinal profile are characterized by poor prognosis and the absence of biomarker for treatment personalization. No CT regimen was superior in terms of PFS in patients with unfavorable CUPs.
•ESMO guidelines classify CUPs with a gastrointestinal profile into favorable and unfavorable subsets.•No CT was superior in terms of PFS in patients with unfavorable CUPs.•Peritoneal metastases were associated with a shorter OS.•Prognostic and predictive molecular determinants are missing.