# Blood-based monitoring of bladder-sparing trimodality therapy for muscle-invasive bladder cancer

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $597,080

## Abstract

PROJECT SUMMARY/ABSTRACT
Although radical cystectomy is often recommended for muscle-invasive bladder cancer (MIBC), a well-tolerated
alternative called bladder-sparing trimodality therapy (TMT), consisting of chemoradiation therapy (CRT) follow-
ing transurethral resection of bladder tumor (TURBT), has equivalent long-term outcomes to cystectomy while
preserving the patient’s native bladder. However, 20-30% of patients treated with TMT require a salvage cystec-
tomy due to recurrent disease, and there is an unmet need for molecular biomarkers to precisely identify appro-
priate candidates and to monitor for recurrences after therapy. We recently developed methods for the microflu-
idic isolation and molecular characterization of circulating tumor cells (CTCs) from blood, which have potential
as non-invasive, serial “liquid biopsies” to predict and monitor therapeutic responses. Our long-term goal is to
develop predictive molecular biomarkers that can precisely guide the individualized care of patients with bladder
cancer. The overall objectives of this application are to (i) optimize CTC and tumor molecular signatures for the
prediction of therapeutic responses and longitudinal monitoring of patients treated with TMT, and (ii) to elucidate
molecular mechanisms of treatment resistance based on the evolution of CTC and tumor molecular profiles after
CRT. Our central hypothesis is that CTC molecular signatures, in combination with tumor molecular profiles, can
predict and monitor therapeutic responses after bladder preservation therapy in patients with MIBC. The rationale
for this project is that the development of molecular biomarkers will enable the tailored selection of therapy and
accurate monitoring of treatment response for MIBC patients. The central hypothesis will be tested by pursuing
three specific aims: 1) Identify pretreatment CTC molecular signatures that, combined with tumor molecular
profiles, correlate with prognosis after TMT; 2) Identify CTC molecular signatures to monitor for early detection
of recurrence after TMT; and 3) Evaluate dynamic changes in CTC and tumor molecular profiles before and after
TMT to elucidate mechanisms of therapeutic resistance. In the first aim, we will optimize pretreatment CTC and
tumor predictive signatures in MIBC patients undergoing TMT, followed by validation in MIBC patients enrolled
in the SWOG/NRG 1806 clinical trial. In the second aim, we will optimize a CTC RNA signature for early detection
of recurrence after TMT in a cohort of MIBC patients, followed by validation in patients enrolled in SWOG/NRG
1806. In the third aim, we will analyze CTC and tumor transcriptional profiles collected longitudinally from TMT
patients who develop recurrent disease to identify molecular signatures associated with therapeutic resistance.
The research proposed in this application is innovative because it will develop novel molecular assays based on
the microfluidic isolation and RNA expression profiling of CTCs i...

## Key facts

- **NIH application ID:** 10366341
- **Project number:** 1R01CA259007-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** David T. Miyamoto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $597,080
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366341

## Citation

> US National Institutes of Health, RePORTER application 10366341, Blood-based monitoring of bladder-sparing trimodality therapy for muscle-invasive bladder cancer (1R01CA259007-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10366341. Licensed CC0.

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