Evaluation of pre-treatment F-18 FDG PET/CT according to Mandard classification in locally advanced rectal cancer patients undergoing neoadjuvant chemoradiotherapy

Abstract

Background: This study primarily aimed to assess whether baseline [(18)F] fluorodeoxyglucose (FDG) PET/CT metabolic parameters-including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)-can predict tumor regression grade (TRG) and survival in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT). In addition, secondary analyses were performed to identify other clinical and pathological variables associated with treatment response and prognosis.

Methods: This retrospective study included patients diagnosed with LARC who underwent nCRT followed by surgical resection between 2014 and 2023. Pre-treatment staging with F-18 FDG PET/CT was performed for all patients. Postoperative pathological response was assessed using the TRG system. Patients were categorized into two groups: complete responders (TRG1) and incomplete responders (TRG2-5). Demographic characteristics, PET/CT metabolic parameters (SUVmax, MTV, TLG), Carcinoembryonic antigen (CEA), Carbohydrate antigen 19 - 9 (CA19-9), and histopathological features (perforation, lymphovascular invasion [LVI], and perineural invasion [PNI]) were compared between the groups. Statistical analyses included chi-square tests, Mann-Whitney U tests, logistic regression models with odds ratios (ORs), and Kaplan-Meier survival analysis.

Results: A total of 151 patients were included. A statistically significant difference was found between TRG1 and TRG2-5 groups regarding family history (p = 0.034), CEA at diagnosis (p = 0.002), Ca19.9 after radiotherapy (p = 0.045), and presence of concurrent chemotherapy (CC) (p = 0.004). Significant differences were also observed in postoperative pathological features, including perforation (p = 0.045), LVI (p = 0.023), PNI (p = 0.031), and post-operative CEA levels (p = 0.001). In terms of outcomes, TRG1 was associated with better survival (p = 0.001), longer disease-free survival (p = 0.001), and overall survival (p = 0.001). Logistic regression identified independent predictors of complete response (TRG1): family history (OR: 5.08, p = 0.027), post-RT CEA (OR: 0.61, p = 0.015), post-op CEA (OR: 1.13, p = 0.012), perforation (OR: 20.93, p = 0.033), LVI (OR: 0.33, p = 0.042), and PNI (OR: 0.49, p = 0.045). Kaplan-Meier analysis demonstrated significantly longer overall survival in patients with TRG1 compared to TRG2-5 (log-rank p = 0.001). Similarly, disease-free survival was significantly better in the TRG1 group (log-rank p = 0.001). In the multivariate Cox regression model, TRG1 (HR: 0.41; 95% CI: 0.26-0.66; p = 0.001), CC (HR: 0.62; 95% CI: 0.39-0.98; p = 0.039), and absence of perforation (HR: 0.51; 95% CI: 0.28-0.95; p = 0.034) were found to be independent predictors of improved survival.

Conclusions: Baseline F-18 FDG PET/CT parameters, including SUVmax, MTV, and TLG, were not predictive of TRG or survival in patients with LARC undergoing neoadjuvant chemoradiotherapy. However, clinical and pathological variables such as family history, post-treatment CEA levels, perforation, lymphovascular invasion, and perineural invasion were significantly associated with TRG1. TRG1, histopathological subtype, perforation, and CC were also found to be independent predictors of survival. These findings suggest that while FDG-PET/CT may have limited utility in predicting treatment response, certain clinical and pathological features remain critical for outcome assessment.

Keywords: (18F) FDG PET/CT; Locally advanced rectal cancer; Mandard classification; Neoadjuvant chemoradiotherapy.

Fig. 1

A Pre-treatment axial F-18 FDG PET/CT image of a patient with TRG1 (complete pathological response). The primary lesion in the rectum shows moderate FDG uptake (SUVmax: 12.3; MTV: 18 mL; TLG: 156). B Pre-treatment axial F-18 FDG PET/CT image of a patient with TRG5 (poor response). The lesion demonstrates intense FDG uptake (SUVmax: 22.7; MTV: 38 mL; TLG: 435)”

Fig. 2

Forest plot of multivariate Cox regression analysis for overall survival. Hazard ratios (HR) and 95% confidence intervals (CI) are shown for independent predictors

Fig. 3

Kaplan–Meier curves for overall and disease-free survival according to tumor regression grade (TRG)