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Prospective evaluation of circulating tumor DNA (ctDNA) in detecting early progression on immune checkpoint inhibitors in patients with advanced genitourinary cancers

Introduction and objective

Immune checkpoint inhibitors (ICI) are approved for the treatment of advanced genitourinary (GU) malignancies. Tumor response to ICI is largely based on conventional scans with known limitations. Signatera is a commercially available personalized and tumor-informed mPCR NGS-based circulating tumor DNA (ctDNA) test (Natera Inc., Austin, TX) that is optimized to monitor tumor status in patient’s blood sample. In this pilot study, we investigate the serial ctDNA detection rate and the concordance of serial ctDNA changes with radiographic response rate of advanced GU patients undergoing ICI treatment. We hypothesize that serial ctDNA testing can accurately predict tumor response to immunotherapy compared with conventional scans.


We prospectively enrolled consecutive advanced GU cancer patients treated with an ICI-based regimen or monotherapy for at least 12 weeks, without evidence of disease progression, available ctDNA test result(s) and CT scans. To monitor ctDNA, patient blood was collected at the time of study entry and every 6-8 weeks until progressive disease occurred and/or until 2 years. Overall response rate (ORR) was assessed. We present the preliminary results after a median follow up of 7.5 months.


Twelve patients [median age 68 (49-81), 75% renal cell, 17% urothelial cancer and 8% prostate cancer] had at least one ctDNA test result at the time of data cut-off. Tumors were more frequently PD-L1 negative (90%), one patient had microsatellite instability with a median tumor mutational burden of 6 (range 3-25) mut/Mb. Patients were on ICI [25% monotherapy, 33% ICI/ICI, 42% ICI/other) for a median of 6.5 months prior to first ctDNA test. Patients had a median number of 5 (range 1-6) ctDNA tests. The table summarizes the ctDNA and overall response rate of the study cohort. Detection rate was 50% and in all cases except one, ctDNA changes were concordant with ORR. One patient had progressive disease in scans with an initial decline in ctDNA, that later increased. At time of data cut-off, 50% discontinued ICI due to disease progression (33%), no evidence of disease (17%) or adverse reactions (8%).


In this pilot study, ctDNA was frequently detected in advanced GU tumors and serial changes in ctDNA were concordant with staging scans to monitor disease response to ICIs.

Source of Funding

This study was supported by Natera, Inc