Introduction:

18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (PET/CT) was reported to have limited utility in clinical N0 patients (pts) with muscle-invasive bladder carcinoma (MIBC) who received neoadjuvant chemotherapy and radical cystectomy (RC) or RC alone (Dason, AUA19). Early findings from the PURE-01 study (pembrolizumab before RC in cT2-3bN0M0 MIBC) reported pathologic complete responses (pT0) in 42% of patients. Herewith we present a secondary analysis aimed at evaluating the role of PET/CT imaging in lymph node involvement assessment.

Methods:

In the PURE-01 study (NCT02736266), 3 courses of 200 mg pembrolizumab, every 3 weeks, were administered prior to RC. Adverse events (AE) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) classification, version 5.0. 

The patients were assessed with standard thorax-abdomen CT scan and with PET/CT scan during screening and after treatment, before RC. PET/CT scan was performed according to European guidelines. Images were acquired from the base of skull to mid-thigh. Imaging review and analysis was performed by two experienced nuclear medicine physicians blinded to clinical information. PET/CT images were evaluated qualitatively for increased or abnormal areas of FDG uptake with corresponding anatomic alterations in CT slices. Semiquantitative and volumetric analysis was performed. For each patient with nodal increased uptake in abdomino-pelvic area, the maximum standardized uptake value (SUVmax) and the short-axis size of the most intense lymph node were recorded.

All pts underwent templated pelvic lymph node dissection (LND) with packeted node submission. 

PET/TC diagnostic ability was assessed using sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy.

Results:

From 02/17 to 06/2019, 114 pts were enrolled ad treated. 11 pts received additional chemotherapy post-pembrolizumab and were excluded from the analyses, resulting in 103 total evaluable pts, accounting for a total of 206 PET/TC scans. Six pts (5.8%) had positive nodes at baseline PET/CT: mean SUVmax=2.75; mean short axis: 6.2 mm. Eight pts (7.8%) had positive nodes at PET/CT post-pembrolizumab: mean SUVmax=4.21; mean short axis: 7.2mm. The rate of pathologic lymph node positive (pN+) disease was 15.5% (16 pts). The performance of post-pembrolizumab PET/CT in predicting pN+ disease is indicated in the Table. Considering pre-treatment PET/CT scan, 4/6 pts (66.7%) showing baseline FDG uptake revealed as pN+ vs 12/97 (12.4%) with no baseline FDG uptakes (p=0.005). A total of 39 pts (37.9%) developed inflammatory FDG-uptakes post-pembrolizumab in several target organs/regions: top 5 sites were thyroid (N=21, 61.8%), stomach and mediastinum (13 pts each, 12.6%), lung (N=10, 9.7%), other lymph nodes (N=4, 3.9%). These changes were clinically evident (signs/symptoms or laboratory changes) in 15 pts (38.5%).

Conclusion:

In clinically N0 pts with MIBC, the features of PET/CT in response assessment post-pembrolizumab recapitulated those after chemotherapy, resulting in limited clinical utility.

However, PET/CT scan may be useful to exclude the few pts who show any nodal FDG-uptake pre-treatment from single-agent checkpoint inhibitor trials, thus refining the conventional CT-scan based screening procedures. Three cycles of pembrolizumab determined profound inflammatory changes, whose long-term impact on safety is still to be determined.

Funding: MERCK