Main Session
Sep 28
SS 08 - GU 2: Bladder and Post-Prostatectomy Radiation

146 - Early Detection of Metastatic Progression by Circulating Tumor DNA in Patients Undergoing Bladder-Preserving Trimodality Therapy

04:45pm - 04:55pm PT
Room 24

Presenter(s)

Dekuang Zhao, DO, PhD Headshot
Dekuang Zhao, DO, PhD - Moffitt Cancer Center, Tampa, FL

D. Zhao1,2, V. M. Khatri1,3, J. Y. Nakashima1,2, J. S. Chadha4, M. S. Chatwal4, J. Zhang4, F. Ionescu4, J. Linscott4, R. Li4, M. Poch4, W. J. Sexton4, A. Yu4, P. Spiess4, L. W. Zemp4, S. M. Gilbert4, B. Manley4, V. Yin5, R. Jain4,6, J. F. Torres-Roca2, P. A. S. Johnstone2, K. Yamoah2, and G. D. Grass2; 1University of South Florida, Tampa, FL, 2Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 3H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 4Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 5Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 6Department of Genitourinary Oncology, Weill Cornell Medicine, New York City, NY

Purpose/Objective(s):

Radical cystectomy (RC) and trimodality therapy (TMT) are efficacious treatment options for muscle invasive bladder cancer (MIBC). Novel and sensitive methods for post-treatment surveillance are needed to detect disease recurrence. This study is to test the clinical value of circulating tumor DNA (ctDNA) for early detection of disease recurrence in post-TMT setting.

Materials/Methods:

We performed a retrospective ctDNA analysis in 42 MIBC patients treated with TMT at Moffitt Cancer Center. Patients were stratified as post-TMT ctDNA (+) or ctDNA (-) and assessed for metastasis-free survival (MFS) and recurrence-free survival (RFS) using the Kaplan-Meier method.

Results:

At a median follow-up of 448 days (range: 100-1555) after TMT, 6 patients (14.3%) were ctDNA (+) and 36 patients (85.7%) were ctDNA (-). 5 of 6 patients in the ctDNA (+) group developed radiographic evidence of metastasis. However, all 36 patients in the ctDNA (-) group remained free of metastasis. Plasma ctDNA positivity correctly identified all patients with metastatic progression with 100% sensitivity and 97.3% specificity. Furthermore, ctDNA-based detection of metastatic progression preceded clinical detection of metastasis with a median lead time of 57 days and a maximal lead time of 139 days. A ctDNA (+) status was associated with worse MFS (p<0.0001) and RFS (p=0.0005). In univariable analysis, ctDNA (+) status was the only predictor for worse RFS (HR 6.36, 95% CI: 1.93-20.96, p=0.0024).

Conclusion:

Plasma ctDNA is a potential biomarker for early detection of metastatic progression in patients undergoing TMT. Our hypothesis generating findings provide the basis for larger clinical studies to evaluate the utility of plasma ctDNA-guided patient surveillance following TMT.