Objective <p>Interim ¹⁸F-FDG PET/CT (iPET/CT) imaging demonstrates potential in assessing the early therapeutic response in lymphoma. Nevertheless, the prognostic significance of interim PET-CT in diffuse large B-cell lymphoma (DLBCL) remains controversial. This study aimed to evaluate whether semi-quantitative PET/CT metabolic parameters and other metrics could enhance the prognostic value of interim PET/CT in DLBCL patients exhibiting partial metabolic remission (PMR).</p> Methods <p>A retrospective analysis was performed from January 2018 to December 2023, focusing on patients with DLBCL who achieved PMR on interim PET-CT. Patient demographics, clinical characteristics, and semi-quantitative PET/CT metabolic parameters were extracted from the medical records. Multivariate analyses were conducted to identify the risk factors associated with failure to achieve complete metabolic remission (CMR) at the end of treatment (EOT). Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cut-off values for continuous predictive variables. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods, and risk factors were evaluated using Cox regression models.</p> Results <p>In a cohort consisting of 80 newly diagnosed DLBCL cases that exhibited PMR on interim PET scans, 50 cases ultimately achieved CMR, while the remaining 30 cases still had positive PET findings at EOT. Analysis revealed that the interim lesion-to-liver maximum standardized uptake value ratio (RLL) and bone marrow involvement were independent prognostic factors for positive PET-CT outcomes at EOT. Notably, an interim RLL threshold greater than 1.66 emerged as a reliable predictor with a sensitivity of 73.3% and a specificity of 72.0%. Additionally, the International Prognostic Index (IPI) and interim RLL were identified as independent prognostic indicators for both progression-free survival (PFS) and overall survival (OS).</p> Conclusion <p>Our study revealed that within the cohort of DLBCL patients exhibiting PMR on interim PET scans, an interim RLL greater than 1.66 and bone marrow involvement emerged as independent risk factors for positive PET results at the end of treatment. Additionally, the IPI and interim RLL were identified as independent prognostic markers for both progression-free survival and overall survival. The integration of clinical characteristics with semi-quantitative PET/CT parameters has the potential to enhance the prognostic role of interim PET/CT exhibiting PMR in DLBCL cases.</p>