Cancer of Unknown Primary Site

Cancer of Unknown Primary Site (CUP) presents unique challenges due to the unidentified origin of metastasis, complicating treatment decisions. Key aspects of its management include:

1. Diagnostic Workup:

• Baseline Evaluation: Involves a comprehensive approach with patient history, physical exams, lab tests, and contrast-enhanced CT scans (chest, abdomen, pelvis) to locate the primary site.

• Pathological Analysis: Immunophenotyping (e.g., immunohistochemistry) remains central, but molecular profiling (e.g., gene expression, next-gen sequencing) is increasingly integrated to predict tissue of origin and identify targetable mutations (e.g., EGFR, ALK, BRCA).

2. Treatment Strategies:

• Site-Specific Therapy: Guided by suspected primary site (e.g., treating as lung cancer if molecular markers suggest it).

• Empirical Chemotherapy: Platinum-based regimens (e.g., carboplatin/paclitaxel) are commonly used for their broad efficacy.

• Targeted Therapy/Immunotherapy: Emerging role for molecularly guided treatments (e.g., PARP inhibitors for BRCA mutations, checkpoint inhibitors for high tumor mutational burden).

3. Prognosis and Research:

• Outcomes remain poor (median survival: 6–12 months), underscoring the need for clinical trials.

• Molecular profiling may improve prognosis in subsets (e.g., HPV-associated squamous cell CUP), but broader validation is needed.

4. Decision-Making:

• Treatment choice depends on clinical-pathologic correlation, molecular findings, and patient fitness. Multidisciplinary input is critical.

Future Directions: Enhanced genomic profiling, liquid biopsies, and trials exploring immunotherapy or targeted agents may refine CUP management.