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BCAN TT 2022: Relationship of Circulating Tumor DNA in Patients with Muscle Invasive Bladder Cancer to Pathologic Staging and Disease Prognosis

(UroToday.com) Dr. Benjamin Miron, MD is a urologic oncology fellow at the Fox Chase Cancer Center in Philadelphia, PA. He is the recipient of the 2021 BCAN Young Investigator Award for his research focused on the role of ctDNA as a marker of pathologic response in patients with muscle invasive bladder cancer being treated with cisplatin-based neoadjuvant chemotherapy.


Complete pathologic response (ypT0N0) after neoadjuvant chemotherapy has strong prognostic implications, with 5-year cancer-specific survival up to 95%. A compelling argument for bladder preservation in such patients can be made, but defining a complete clinical response with modern staging techniques (CT/MRI and biopsy) is notoriously unreliable.

A prospective clinical trial at Fox Chase Cancer Center used systematic endoscopic evaluation (SEE) to assess pathologic response after cisplatin-based neoadjuvant chemotherapy. Notably, half of residual MIBC lesions would have been missed by this systematic post-treatment biopsy protocol, which was attributable to subclinical submucosal tumors.

Circulating tumor DNA (ctDNA) represents a non-invasive biomarker capable of detecting minimal residual disease after therapy in a number of solid cancer states, correlating with poor prognosis and disease recurrence. This technique can be performed in a tissue informed manner whereby the primary tumor is initially sequenced to inform specific mutation targets, or using a tissue agnostic approach which utilizes a ubiquitous tumor signature to detect mutations. 

Prior work has established ctDNA as a prognostic marker at three specific time points- at baseline, prior to cystectomy, and after cystectomy. The primary aim of this study was to correlate undetectable ctDNA prior to cystectomy with pathologic complete response (pCR) rates. Patients at Fox Chase Cancer Center with MIBC and high risk NMIBC undergoing radical cystectomy had pre-operative ctDNA assays collected. The primary endpoint was associated with pCR, with secondary endpoints including characterization of ctDNA with tumor sequencing results and correlation with survival. 

Thus far, specimens have been prospectively collected from 38 patients with MIBC and 17 patients with high-risk NMIBC, and we eagerly await further analysis which is pending. Further work will define the role of ctDNA as a predictive biomarker after systemic therapy to inform bladder preservation. The investigators also plan to investigate the biology of ctDNA shedding tumors. The addition of this biomarker to contemporary staging modalities, including imaging and repeat biopsy, will further improve our ability to detect occult residual invasive disease and triage, such patients, for appropriate definitive radical cystectomy rather than bladder preservation.

Presented by: Dr. Benjamin Miron, MD, a urologic oncology fellow at the Fox Chase Cancer Center in Philadelphia, PA

Written by: Patrick Hensley, MD, Urologic Oncologist at the University of Kentucky (@pjhensley11) with Ashish Kamat, MD, Urologic Oncologist at MD Anderson Cancer Center (@UroDocAsh) during the 2022 Bladder Cancer Advocacy Network Think Tank (#BCANTT22) Wednesday Aug 3 – Friday Aug 5, 2022 

References:

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