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

## TL;DR

This study examines survival factors in cancer patients whose original tumor site is unknown, using clinical data from before modern molecular testing.

## Contribution

The study identifies clinical and laboratory factors that predict survival in cancer of unknown primary patients before molecular diagnostics were common.

## Key findings

- General health status, blood tests, and inflammation markers strongly influence survival in cancer of unknown primary patients.
- ECOG score, elevated ALP, calcium levels, and NLR are independent predictors of poorer survival.
- The median overall survival was 7.1 months with significant disparities based on clinical factors.

## Abstract

Cancer of unknown primary is a rare and challenging condition in which the cancer has already spread, but its original site cannot be identified. Despite advances in cancer diagnostics, the survival of these patients has remained poor for many years. In this study, we analyzed real-world clinical data from patients treated before modern molecular testing was widely available, in order to identify simple clinical and laboratory factors that influence survival at the time of diagnosis. We found that general health status, routine blood test results, and markers of inflammation were strongly associated with patient outcomes. These findings highlight that widely available clinical information can help estimate prognosis and support treatment decisions early in the disease course. Our results provide a useful reference point for clinicians and researchers and may serve as a baseline for comparison with outcomes in the current era of molecularly guided therapies.

Background: 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. Methods: 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. Results: 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, p = 0.016), elevated ALP (HR = 1.81, 95% CI: 1.20–2.74, p = 0.005), elevated calcium level (HR = 2.08, 95% CI: 1.05–4.13, p = 0.037), and NLR ≥2.61 (HR = 2.55, 95% CI: 1.67–3.89, p < 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, p = 0.054). Conclusions: This study provides insights into the survival and prognostic factors influencing CUP patients, assisting clinicians in treatment eligibility assessments and guiding future investigations.