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CUP Molecular Profiling — SCE Medical Oncology MCQ

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HardCancer of Unknown PrimaryCUP Molecular ProfilingSCE Medical Oncology

A 60-year-old man presents to the CUP clinic with adenocarcinoma of unknown primary. Comprehensive molecular profiling reveals a tissue-of-origin prediction of pancreaticobiliary origin with high confidence. Should he be treated with a pancreaticobiliary-specific regimen rather than empiric CUP chemotherapy?

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Correct answer: C — Molecular profiling-guided, site-specific therapy is an evolving approach — the CUPISCO trial is evaluating this, and selected patients with high-confidence tissue-of-origin predictions may benefit from site-specific therapy

The CUPISCO trial is a prospective randomised trial evaluating molecular profiling-guided site-specific therapy versus empiric platinum-doublet chemotherapy for CUP. Early results suggest improved outcomes with targeted therapy when a high-confidence tissue-of-origin prediction is available. Molecular classifiers (CancerTYPE ID, CUP-AI) achieve >85% accuracy in predicting tissue of origin. While not yet standard of care, this approach is increasingly used in clinical practice for CUP with actionable molecular targets.

Reference: ESMO 2024 CUP Guidelines; CUPISCO trial; Fizazi et al JCO 2019