Pretreatment 18F-FDG PET/CT Radiomics for Predicting Response to First-Line Targeted Therapy Plus Immunotherapy in Metastatic Renal Cell Carcinoma

Patients with metastatic renal cell carcinoma may have different responses to first-line treatment combining a tyrosine kinase inhibitor with an immune checkpoint inhibitor. Differences may also occur among the primary renal tumor and metastatic lesions within the same patient. Pretreatment 18F-FDG PET/CT provides whole-body information about tumor glucose metabolism, while radiomics can extract quantitative imaging features that may reflect tumor heterogeneity.

This is a single-center retrospective observational cohort study using existing clinical, pathological, treatment, follow-up, and pretreatment 18F-FDG PET/CT data. Eligible patients had pathologically confirmed metastatic renal cell carcinoma, underwent 18F-FDG PET/CT before starting first-line TKI plus ICI therapy, had at least one measurable lesion according to RECIST version 1.1, and had adequate treatment-response and follow-up information. The study did not assign treatment or alter routine clinical care.

Primary renal tumors and eligible metastatic lesions are segmented separately on pretreatment PET/CT images. Conventional metabolic parameters and radiomic features are extracted from each lesion. For patients with multiple metastatic lesions, lesion-level features are aggregated to generate patient-level variables. Primary-tumor, metastatic-lesion, and combined multi-lesion radiomics models are developed. Clinical and metabolic variables are also evaluated, and a combined prediction model is constructed. Patients are divided into training and internal validation cohorts for model development and evaluation.

The primary outcome is treatment response assessed approximately 12 weeks after treatment initiation according to RECIST version 1.1. Complete response and partial response are classified as responder status, while stable disease and progressive disease are classified as non-responder status. Progression-free survival is also evaluated to explore whether the prediction model is associated with longer-term treatment benefit.

Inclusion criteria

• Pathologically confirmed metastatic renal cell carcinoma.
• Pretreatment 18F-FDG PET/CT performed before initiation of first-line systemic therapy.
• Receipt of first-line tyrosine kinase inhibitor plus immune checkpoint inhibitor combination therapy.
• At least one measurable lesion according to RECIST version 1.1.
• Available clinicopathological, imaging, treatment response, and follow-up data.

Exclusion criteria

• Receipt of systemic anticancer therapy before the pretreatment 18F-FDG PET/CT examination.
• An interval of more than 1 month between pretreatment PET/CT and initiation of first-line systemic therapy.
• Unavailable treatment response assessment or follow-up data.
• Incomplete key clinicopathological or imaging information.
• PET/CT image quality inadequate for lesion segmentation or radiomics analysis.