Ten-Year Experience in the Treatment of Cancers of Unknown Primary from Poland: From Overall Survival to Factors Influencing Response in the Prepersonalization Era

<b>Background:</b> Cancer of unknown primary represents 3-5% of all cancer cases. This study aimed to identify the clinical and pathological factors affecting survival in these patients before the introduction of next-generation sequencing in modern molecular diagnostics. <b>Methods:</b> A retrospective cross-sectional observational study involving 149 patients with CUP at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, was conducted between 2006 and 2016. Clinical records were analyzed to gather demographic, clinical, and pathological data. Statistical analyses, including the Kaplan-Meier method, estimated overall survival (OS), and Cox proportional hazards modeling, were used to identify significant clinical factors associated with survival. <b>Results:</b> The mean age was 59 years, and 57% of the patients were male. Most patients (59.44%) had an ECOG of 0-1. The most common metastatic sites were the lymph nodes (63.64%), liver (41.26%), bones (23.78) and lungs (21.68%). The median overall survival for the cohort was 7.1 months, with notable survival disparities based on several clinical and laboratory factors. Multivariate analysis revealed that ECOG score >1 (HR = 1.69, 95% CI: 1.10-2.60, <i>p</i> = 0.016), elevated ALP (HR = 1.81, 95% CI: 1.20-2.74, <i>p</i> = 0.005), elevated calcium level (HR = 2.08, 95% CI: 1.05-4.13, <i>p</i> = 0.037), and NLR ≥2.61 (HR = 2.55, 95% CI: 1.67-3.89, <i>p</i> < 0.001) were independent predictors of poorer survival. Elevated LDH showed a consistent trend toward poorer survival but did not reach significance in the fully adjusted model (HR = 1.50, 95% CI: 0.99-2.27, <i>p</i> = 0.054). <b>Conclusions:</b> This study provides insights into the survival and prognostic factors influencing CUP patients, assisting clinicians in treatment eligibility assessments and guiding future investigations.