Total Lesion Glycolysis (TLG) on 18F-FDG PET/CT as a Potential Predictor of Pathological Complete Response in Locally Advanced Rectal Cancer After Total Neoadjuvant Therapy: A Retrospective Study

<b>Background:</b> The accurate prediction of pathological complete response (pCR) following total neoadjuvant therapy (TNT) is crucial for optimising treatment protocols in locally advanced rectal cancer (LARC). Although conventional imaging techniques such as MRI show limitations in assessing treatment response, metabolic imaging utilising 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) provides distinctive information by quantifying tumour glycolytic activity. This study investigates the predictive value of sequential 18F-FDG PET-CT parameters, focusing on Total Lesion Glycolysis (TLG), in predicting pCR after TNT. <b>Methods:</b> We conducted a retrospective analysis of 33 LARC patients (T3-4/N0-1) treated with TNT (neoadjuvant-chemoradiation followed by consolidation FOLFOX chemotherapy). Sequential PET-CT scans were performed at baseline, interim (after 4 cycles of FOLFOX), and post-TNT. Metabolic parameters, including maximum standardised uptake value (SUVmax) and TLG, were measured. Receiver operating characteristic (ROC) analysis assessed the predictive performance of these parameters for pCR. <b>Results:</b> The pCR rate was 21.2% (7/33). Post-TNT TLG ≤ 10 demonstrated excellent predictive accuracy for pCR (AUC 0.887, 92.3% sensitivity, 85.7% specificity, and 96.0% PPV), outperforming SUVmax (AUC 0.843). Interim TLG ≤ 10 also showed a strong predictive value (AUC 0.824, 100% sensitivity, and 71.4% specificity). <b>Conclusions:</b> TLG may serve as a reliable metabolic biomarker for predicting pathologic complete response (pCR) after total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC). Its inclusion in clinical decision-making could improve patient selection for organ preservation strategies, thereby reducing the need for unnecessary surgeries in the future. However, given that the study is based on a small retrospective design, the findings should be interpreted with caution and used alongside other decision-making tools until more comprehensive data are collected from larger studies.