FDG-PET as a tool to predict pelvic lymph node involvement in patients with muscle-invasive bladder cancer

This study evaluated the ability of fluoro-deoxy-glucose positron emission tomography (FDG-PET) to predict pelvic lymph node involvement (LNI) in neoadjuvant trials for muscle-invasive bladder cancer (MIBC). Results indicate comparable accuracy to computed tomography (CT) scans, while FDG-PET had a lower prediction ability than CT in the presacral LN region and in patients with variant histology pre-therapy. However, a pre-therapy FDG uptake was a significant predictor of pathological LNI in pre-therapy CT-negative patients and was associated with event-free and overall survival.

Standard computed tomography (CT) imaging exhibits low sensitivity and specificity in predicting pathological pelvic lymph node involvement (LNI) in patients with muscle-invasive bladder cancer (MIBC). Despite reported limitations of FDG-PET in MIBC according to major guidelines (ASCO, NCNN, and EAU), previous findings from the PURE-01 trial suggested a potential application for FDG-PET in excluding specific patients (T2-4N0M0 with pelvic LN uptake) from neoadjuvant trials involving immune-checkpoint inhibitors (ICI). This study aimed to expand on these insights, investigating the applicability of FDG-PET across a broader range of experimental therapies for MIBC.

Methods

This study collected the data of patients with clinical stage T2-4N0-1M0 MIBC included in past and ongoing neoadjuvant trials, including single agent or combination of ICIs, ICI+chemotherapy, standard chemotherapy and sacituzumab govitecan. All patients had predominant urothelial carcinoma histology and were staged with standard thorax-abdomen CT scan and with PET/CT scan during screening and after treatment, before radical cystectomy. PET/CT images were evaluated qualitatively for increased or abnormal areas of FDG uptake with corresponding anatomic alterations in CT slices. All patients underwent templated pelvic lymph node dissection (LND) with packeted node submission. Multivariable logistic regression analyses and Cox regression analyses were performed for pathological pelvic LNI prediction, event-free survival (EFS) and overall survival (OS).

Results

This study included 149 patients (298 PET scans). Of those, 112 patients (75.2%) received ICI, 26 (17.4%) ICI plus chemotherapy, and 11 (7.4%) the remaining therapies. Twenty patients (13%) and sixteen patients (11%) had PET+ pre- and post-therapy, respectively. FDG-PET and CT scans demonstrated comparable accuracy in predicting LNI pre- (85.3% vs. 86.7%) and post-therapy (86.7% vs. 84.6%). The combination of the two procedures did not improve the accuracy (87.3% pre-therapy and 88.7% post-therapy). No differences in accuracy were detected between PET and CT for common, external, internal iliac, and obturator fossa LN. However, PET showed lower accuracy in predicting presacral LNI compared to CT, both pre-therapy (76.6% vs. 88.8% with PET and CT, respectively) and post-therapy (75.8% vs. 86.6%) and in patients with variant histology pre-therapy (84.3% vs. 90.9%). In a multivariate analysis, a pre-therapy FDG uptake significantly predicted a pathological LNI in the pre-therapy CT-negative T2-4N0M0 cohort (AUC: 0.84). No significant differences were found depending on the type of treatment (immunotherapy vs. other; OR[95%CI]:0.5[0.17-1.47;p= 0.2). In the pre-therapy CT negative cohort, variations in 36-month EFS and OS were observed based on the positivity or negativity of pre-therapy PET. Notably, patients displaying pre-therapy negative CT scans but positive PET results experienced lower EFS and OS rates.

Conclusions

Despite the higher sensitivity of pre- and post-therapy with FDG-PET, there was no difference in accuracy between CT and PET to detect pelvic LNI in patients with MIBC. FDG-PET had a lower prediction ability of LNI than CT in the presacral LN region (pre-and post-treatment) and in patients with variant histology (pre-therapy). A pre-therapy FDG uptake was a significant predictor of pathological LNI in pre-therapy CT-negative patients in multivariate analysis, and was associated with EFS and OS. This information should be critically considered for patient selection in neoadjuvant therapy trials.

Reference

Cigliola A, Basile G, Mercinelli C, et al. Utility of fluoro-deoxy-glucose positron emission tomography (FDG-PET) to predict a pelvic lymph node involvement (LNI) in patients (pts) with muscle-invasive bladder cancer (MIBC) enrolled in neoadjuvant therapy trials. Presented at ASCO GU; Abstract 527.