Advances in cancer treatments, including immunotherapies, targeted therapies, and antibody-drug conjugates, have improved overall survival (OS) rates for patients with advanced cancers. However, accurately estimating life expectancy at baseline remains a significant challenge. These patients often have limited treatment options, making precise prognostic tools crucial for patient selection and guiding treatment decisions. There is a pressing need to develop reliable biomarkers that can predict OS at baseline, helping to refine life expectancy estimates and improve clinical outcomes.

Baseline tumor burden has emerged as a key prognostic marker for OS in cancer patients [1,2]. It represents the total amount of cancer in the body and can be measured through imaging, LB, or by quantifying tumor-derived markers [1,3]. Early identification of patients with higher tumor burden may help improve patient stratification at baseline and optimize treatment decisions.

CT tumor burden, represented by total tumor volume (TTV), provides a comprehensive assessment of tumor load, taking into account both the size and number of lesions, using computed tomography (CT). Several studies have demonstrated the prognostic value of TTV for OS in solid tumors [[4], [5], [6], [7]].

In parallel, liquid biopsy (LB) provides a comprehensive analysis of tumors. Specifically, the analysis of circulating tumor DNA (ctDNA), has transformed cancer care by providing a non-invasive method for tracking tumor dynamics [8]. ctDNA, shed by tumor cells, carries tumor-specific mutations and offers real-time insights into tumor status [9]. The proportion of ctDNA in the bloodstream, referred to as tumor fraction (TF), serves as a dynamic marker of tumor activity and can vary widely among patients [[10], [11], [12]], which makes ctDNA a valuable tool for monitoring disease progression and OS outcomes. Despite the individual utility of ctDNA and TTV, no study has directly compared their combined prognostic value in patients with metastatic solid tumors at baseline.

The purpose of this study was to explore whether combining liquid biopsy ctDNA and TTV (representing CT tumor burden) provides a more refined prognostic tool at baseline for patients with metastatic solid tumors, compared to using either liquid biopsy or TTV alone, to improve life expectancy predictions.