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CUP Prostate Origin — SCE Medical Oncology MCQ

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EasyCancer of Unknown PrimaryCUP Prostate OriginSCE Medical Oncology

A 55-year-old man presents with bone metastases from an unknown primary. PSA is markedly elevated at 450 ng/mL. IHC on bone biopsy shows PSA+, NKX3.1+. What is the management?

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Correct answer: D — Treat as metastatic prostate cancer with ADT ± novel hormonal agent — markedly elevated PSA and NKX3.1 positivity is diagnostic of prostate origin regardless of whether a prostate primary is identified on imaging

Markedly elevated PSA (>20 ng/mL) with NKX3.1 and/or PSA immunohistochemical positivity on biopsy is virtually pathognomonic for prostate cancer origin. This represents a 'favourable CUP subset' that should be treated with standard prostate cancer protocols (ADT + ARPI or chemotherapy depending on disease volume) rather than empiric CUP chemotherapy. MRI of the prostate may be performed but should not delay treatment initiation. Response to ADT confirms the diagnosis.

Reference: NICE NG36 CUP; ESMO 2024 CUP and Prostate Cancer Guidelines