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Updated: Jun 27, 2025
07:48
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
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Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer
Andrew T Lenis1,2, Karissa Whiting3, Vignesh Ravichandran4
1Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY.
JCO Precision Oncology
|May 1, 2024
Summary
Patients with chemotherapy-resistant bladder cancer may avoid adjuvant therapy if their disease is organ-confined and lacks lymphovascular invasion (LVI). Genomic analysis reveals therapeutic targets for this poor-prognosis group.
Area of Science:
- Uro-oncology
- Medical genomics
- Cancer treatment
Background:
- Muscle-invasive bladder cancer (MIBC) after neoadjuvant chemotherapy (NAC) and radical cystectomy presents a poor prognosis.
- Adjuvant therapy data for these patients remain conflicting, necessitating further investigation.
- Understanding the genomic landscape of chemotherapy-resistant bladder cancer is crucial for guiding management and clinical trials.
Purpose of the Study:
- To evaluate the natural history of chemotherapy-resistant bladder cancer.
- To analyze the genomic landscape of chemotherapy-resistant bladder cancer.
- To inform patient management and clinical trial design for MIBC patients with residual disease.
Main Methods:
- Retrospective analysis of MIBC patients treated with NAC and cystectomy (2001-2019).
- Kaplan-Meier and Cox proportional hazards models assessed recurrence-free survival (RFS).
- Targeted exome sequencing analyzed genomic alterations in post-NAC specimens.
Main Results:
- Lymphovascular invasion (LVI) was the strongest predictor of RFS (HR, 2.15).
- Patients with ypT2N0 disease without LVI showed prolonged RFS (70% at 5 years).
- Chemotherapy-resistant tumors had fewer DNA damage response gene alterations than chemotherapy-naïve tumors (15% vs. 29%; P=.021).
- CDKN2A/B alterations correlated with shorter RFS; PIK3CA alterations with LVI.
Conclusions:
- Organ-confined disease without LVI may allow for close observation without adjuvant therapy in chemotherapy-resistant bladder cancer.
- The genomic profile of chemotherapy-resistant tumors resembles that of chemotherapy-naïve tumors.
- Targeted therapies offer potential adjuvant treatment opportunities for chemotherapy-resistant bladder cancer.
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