The PURE-01 study (NCT02736266) was a trial testing single-agent neoadjuvant immunotherapy with pembrolizumab in MIBC. Updated results of this trial showed a pathologic complete response rate of 37%.2 An imaging biomarker program focused on staging and response evaluation was included in the PURE-01 trial. The evaluation of the role of PET/CT to predict LNI, which is presented in this study,3 represented one of the objectives of this project.
Patients enrolled in PURE-01 were staged with PET/CT scan, contrast-enhanced thorax-abdomen CT scan, and bladder multiparametric MRI during screening and after 3 cycles of pembrolizumab, before radical cystectomy (RC) plus extended pelvic lymph node dissection. Since the PURE-01 trial enrolled patients with clinical stage (c) T2-4aN0M0, the role of PET/CT in predicting LNI was assessed in a population with cN0 disease at traditional imaging techniques. Lymph nodes were judged suspicious for malignancy whenever an increased uptake was found irrespective of the size on CT scan.
A total of 108 patients and 105 patients had evaluable baseline and post-pembrolizumab scans, respectively. In total, 14% showed pathologic lymph nodes (pN+) on RC.
After images were reviewed, 7 patients (6.5%) revealed a baseline FDG uptake consistent with clinically positive lymph nodes (cN+) (mean SUVmax 2.6; mean short axis 6 mm), while after pembrolizumab 8 patients had cN+ disease (mean SUVmax 3.9; mean short axis 7 mm).
Considering pretreatment PET/CT, 4 of 7 patients (57%) with baseline FDG uptake had pN+ vs. 11 of 101 (11%) with no uptakes. Both pre- and post-pembrolizumab PET/CT significantly predicted LNI at univariate analyses. However, the sensitivity to detect LNI was 27% and 37.5% for pre- and post-pembrolizumab PET/CT.
PET-CT showed high specificity (97% and 98% for pre- and post-therapy PET/CT, respectively), and false-positive rate of post pembrolizumab scans was low. This was an unexpected result since it is known that immune stimulation can lead to inflammatory reactions and lymphoid tissue can be particularly affected.
Our results suggest that considering the low sensitivity, PET/CT may not be useful to routinely stage patients with cN0 MIBC. However, in the context of clinical trials, due to its high specificity, PET-CT could increase our ability to select patients for neoadjuvant single-agent immune checkpoint inhibitors by excluding a few more patients (approximately 7%) with suspicious cN+, for whom more aggressive treatment may be needed. Validation of our results in larger datasets is needed.
Written by: Laura Marandino, Antonella Capozza, Marco Bandini, Daniele Raggi, Elena Farè, Filippo Pederzoli, Andrea Gallina, Umberto Capitanio, Marco Bianchi, Giorgio Gandaglia, Nicola Fossati, Maurizio Colecchia, Patrizia Giannatempo, Gianluca Serafini, Barbara Padovano, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Alessandra Alessi, Andrea Necchi
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Department of Nuclear Medicine - PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Unit of Urology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy., Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Unit of Urology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
- Dason S, Wong NC, Donahue TF, et al. Utility of Routine Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography in Identifying Pathological Lymph Node Metastases at Radical Cystectomy. J Urol. 2020;204(2):254-259. doi:10.1097/JU.0000000000001006
- Necchi A, Raggi D, Gallina A, et al. Updated Results of PURE-01 with Preliminary Activity of Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Carcinoma with Variant Histologies. Eur Urol. 2020;77(4):439-446. doi:10.1016/j.eururo.2019.10.026
- Marandino L, Capozza A, Bandini M, et al. [18F]Fluoro-Deoxy-Glucose positron emission tomography to evaluate lymph node involvement in patients with muscle-invasive bladder cancer receiving neoadjuvant pembrolizumab [published online ahead of print, 2020 Oct 15]. Urol Oncol. 2020;S1078-1439(20)30472-5. doi:10.1016/j.urolonc.2020.09.035