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Trimodality Therapy - Bladder Cancer

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Embracing Trimodal Therapy as a Viable Alternative to Radical Cystectomy

Leslie Ballas | May 16, 2024

For years, the standard treatment for muscle-invasive bladder cancer (MIBC) was radical cystectomy (RC), preceded by neoadjuvant cisplatin-based chemotherapy (NAC), if tolerable. Currently, the National Comprehensive Cancer Center (NCCN) has two category 1 recommendations for patients with cT2-T4aN0 MIBC: NAC followed by cystectomy, and trimodal therapy (TMT).1

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Leslie BallasLeslie Ballas, MD, Dr. Ballas is a Radiation Oncologist at Cedars Sinai Medical Center in Los Angeles, California who specializes in the treatment of genitourinary cancers. Dr. Ballas is both a clinician and clinical investigator studying bladder preservation with Trimodality Therapy (TMT), the use of adjuvant radiotherapy (RT) following cystectomy, and radiotherapy effects on bladder cancer patients.
Videos
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Clinical Conversations by Experts
Managing Radiation Toxicity After Trimodal Therapy for Bladder Cancer - Antoine Van Der Heijden & Neha Vapiwala
EV-PRIME Assesses Safety and Efficacy of Combined Systemic and Local Therapy in MIBC - Raj Satkunasivam
Tracking Circulating Tumor DNA in Patients Undergoing Chemoradiation for Bladder Cancer - Kent Mouw
Assessing Baseline Bladder Function for Patients Considering Trimodal Therapy - Comron Hassanzadeh
Examining Guidelines on Radiotherapy for Bladder Cancer with Carcinoma In Situ - Constance Huck
RNA and DNA Biomarkers in Trimodal Therapy for Bladder Cancer - Kent Mouw
Cost-Effectiveness Comparison of Bladder Preservation vs Radical Surgery - Daniel Joyce
The State of Bladder Preservation in High Grade Non-Muscle Invasive Bladder Cancer and Localized Muscle Invasive Bladder Cancer - Leslie Ballas, Parminder Singh & Mark Tyson
Safety of Combining Radiotherapy with Antibody Drug Conjugates in Advanced Urothelial Carcinoma - Neil Desai
Trimodality Therapy Preserves Bladder in High-Grade T1 Bladder Cancer Patients - Douglas Dahl
Quality of life after Trimodality Therapy - Kimberley Mak
Trimodal Therapy in Urothelial vs Non-Urothelial Bladder Cancer - Mario de Angelis
Bladder-Sparing Chemoradiation for Localized Bladder Cancer: Addressing the Unmet Need - Brent Rose
Pembrolizumab + Chemoradiation vs. Trimodality Therapy for Muscle-Invasive Bladder Cancer: The KEYNOTE-992 Trial - Neal Shore
Genomic Tumor Correlates of Response to Trimodal Therapy for Muscle-Invasive Bladder Cancer - Sophia Kamran
Bladder Cancer's Dual Approach: How Radiation and Immunotherapy Are Changing the Game, Discussion - Brian Baumann, Parminder Singh, & Scott Delacroix
Radiation Therapy for Local Recurrence and for Oligometastatic Bladder Cancer - Brian Baumann
Unraveling the Complexities of Treating Node Positive Bladder Cancer Presentation - Monika Joshi
A Clinical Exploration of Radiation and Trimodality Therapy in Bladder Cancer Presentation - Scott Delacroix
Radical Cystectomy Versus Trimodality Therapy for Muscle-Invasive Bladder Cancer: A Multi-Institutional Propensity Score Matched and Weighted Analysis - Jason Efstathiou & Alexandre Zlotta
Comparative Analysis of Radical Cystectomy and Trimodality Therapy for Muscle-Invasive Bladder Cancer, Journal Club – Rashid Sayyid & Zachary Klaassen
The Role of Bladder-Sparing Trimodality Therapy - Sophia Kamran
Comparative Effectiveness of Radical Cystectomy and Trimodality Therapy for Muscle-Invasive Bladder Cancer – Boris Gershman
Physician-Scientist Commentaries
Peer-reviewed Abstract Supplemental Commentaries
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radiation therapy can be an effective way to eliminate the need for radical surgery in bladder cancer patients. Trimodality therapy (TMT) is a bladder-preserving treatment that consists of maximal transurethral resection of bladder tumor (TURBT) followed by chemoradiation. Identifying biomarkers predicting tumor response to different treatments can enable selecting patients
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients with clinically node-positive (cN+) bladder cancer have a worse prognosis than patients without node involvement. Nevertheless, most treatments are more established in patients with node-negative bladder cancer. This includes favorable bladder-sparing protocols that consist of transurethral resection of bladder tumor followed by radical dose radiotherapy with a concurrent radiosensitizing agent.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radical cystectomy and Trimodality therapy, which combines transurethral resection of the bladder tumor (TURBT) and concurrent chemoradiation, are effective treatments for muscle-invasive bladder cancer (MIBC). A recent study investigated the outcomes of patients with MIBC who were eligible for both treatment options.
Written by Alexandre Zlotta MD & Jason Efstathiou MD
Radical cystectomy is widely used in muscle-invasive bladder cancer management, but even with improvements in surgical technique, it remains a major operation with significant morbidity, perioperative mortality, and quality of life-altering changes. Bladder preservation has been evaluated as a treatment for muscle-invasive bladder cancer since the 1980s
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Accurate staging of bladder cancer tumors is essential for guiding treatment decisions. The gold standard for diagnosis and staging is currently biopsy following transurethral resection of bladder tumor (TURBT) and cystoscopy. MRI and CT are imaging techniques that can be used for detection and staging, but challenges in determining
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Therapeutic blockade of PD-1, a receptor on T cells that inhibits tumor suppressive activity, has been highly effective in treating many different types of cancer. Pembrolizumab is a monoclonal antibody that targets PD-1. This type of treatment is particularly valuable for patients who are ineligible for chemotherapy, including patients with muscle-invasive bladder cancer (MIBC).
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine
Transurethral resection of bladder tumor (TURBT) is therapeutic in non-muscle invasive bladder cancer (NMIBC), but the role of repeat TURBT (reTURBT) in MIBC patients remains poorly understood. TURBT with concurrent radiotherapy and chemotherapy can contribute to bladder preservation.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Definitive treatment of muscle-invasive bladder cancer (MIBC) involves cystectomy or radiotherapy. The Bladder Cancer 2001 (BC2001) is a large bladder preservation trial comparing the efficacy of chemoradiotherapy with 5-fluorouracil (5FU) and mitomycin C (MMC) to radiotherapy alone.
Written by Bishoy M. Faltas
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
Systemic chemotherapy is the mainstay of treatment of metastatic bladder cancer. In a recent study, Fischer-Valuck et al. examined the role of local radiation therapy to the primary tumor in patients with metastatic bladder cancer treated with chemotherapy.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Patients who received prior pelvic radiation (XRT) for prostate cancer are at higher risk of developing secondary bladder cancers (SBCs). It was thought that radiation-induced SBCs would lead to a more aggressive phenotype and worse clinical outcomes than primary bladder cancers.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Radiation therapy is a cornerstone of bladder-sparing treatment regimens for patients with muscle-invasive bladder cancer (MIBC). However, a significant number of MIBCs are radioresistant. Components of tumor immune microenvironment (TIME)
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Two key methods to preserve tumor tissues in biobanks are broadly adopted: formalin-fixation and paraffin-embedding (FFPE) and optimal cutting-temperature compound (OCT)- embedding and subsequent freezing, of the tissue specimens. Multiple proteins can be quantified simultaneously from the same sample using mass spectrometry (MS).
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Bladder preservation therapy is a definitive treatment option for clinically localized bladder cancer.
Conference Coverage
Conference Highlights Written by Physician Scientists
Presented by Stephen Boorjian, MD; Janet Kukreja, MD, MPH; and Leslie Ballas, MD
The 2026 American Urologic Association (AUA) Annual Meeting was host to the annual AUA-International Bladder Cancer Group (IBCG) bladder cancer forum. Following a case presentation by Dr. Stephen Boorjian, Drs. Janet Kukreja and Leslie Ballas debated the timely topic of managing toxicities following radiation therapy within the context of trimodality therapy (TMT) for muscle-invasive bladder cancer (MIBC) – who and how?
Presented by Neha Vapiwala, MD, FASTRO
The 2026 European Association of Urology (EAU) annual meeting featured a rapid fire debate session on common problems and controversies in bladder cancer, moderated by Drs. Ashish Kamat and Arnulf Stenzl, and a presentation by Dr. Neha Vapiwala discussing radiation toxicity after trimodal therapy for muscle invasive bladder cancer and that radiation oncologists can and should take responsibility.
Presented by Antoine van der Heijden, MD, PhD
The 2026 European Association of Urology (EAU) annual meeting featured a rapid fire debate session on common problems and controversies in bladder cancer moderated by Drs. Ashish Kamat and Arnulf Stenzl, and a presentation by Dr. Antoine van der Heijden discussing radiation toxicity after trimodal therapy for muscle invasive bladder cancer and the role of the urologist in managing the consequences.
Presented by Gopakumar Iyer, MD
The 2024 American Society for Radiation Oncology (ASTRO) annual meeting held in Washington D.C., was host to the session Presidential Symposium: Innovations in Genitourinary Cancers: Session II - Bladder Preservation - A Modern Choice for Patients. Dr. Gopakumar Iyer discussed how to Integrate Novel Therapeutics with trimodal therapy (TMT).
Presented by Leslie Ballas, MD, FASTRO
The 2024 ASTRO annual meeting was host to the session Presidential Symposium: Innovations in Genitourinary Cancers: Session II - Bladder Preservation - A Modern Choice for Patients. Dr. Leslie Ballas opened this session with a talk titled: Bladder Preservation - A Modern Choice for Patients.
Presented by Kent Mouw, MD, PhD
The 2024 IBCN annual meeting included a session on advancements in circulating biomarkers, featuring a presentation by Dr. Kent Mouw discussing the correlation of ctDNA dynamics with clinical response in muscle-invasive bladder cancer patients undergoing trimodality therapy.
Presented by Brent Rose, MD
The 2024 ASCO annual meeting featured a session on optimizing treatment for your patient with urothelial cancer, and a presentation by Dr. Brent Rose discussing bladder sparing treatment strategies for localized urothelial cancer. Organ preservation is common in many other cancers, including laryngeal cancer, anal cancer, and rectal cancer.
Presented by Jason A. Efstathiou, MD, DPhil
(UroToday.com) The 2022 ASTRO annual meeting featured a session on bladder and kidney preservation, including a presentation by Dr. Jason Efstathiou discussing a multi-institutional matched comparison of radical cystectomy to trimodality therapy for muscle invasive bladder cancer. 
Presented by Alexandre Zlotta
(UroToday.com) Prior randomized controlled trials comparing bladder preservation to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) closed due to lack of accrual. None are foreseen in the near future. Thus, we aimed to compare trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to radical cystectomy (RC) in matched cohorts of patients with MIBC.
Presented by Sophia C. Kamran, MD
(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, Dr. Sophia Kamran presented in a session highlighting novel therapies in bladder cancer and their toxicities, discussing the role of bladder-sparing trimodality therapy with a focus on toxicity and functional outcomes.
Presented by Alexandre R. Zlotta, MD, PhD
(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focusing on urothelial carcinoma, Dr. Zlotta presented a comparison of radical cystectomy and trimodality therapy in the treatment of patients with muscle-invasive bladder cancer (MIBC) in a session focused on a Potpourri of Hot Topics in Urothelial Carcinoma.
Presented by Jason Efstathiou, MD, DPhil
The 2021 ASTRO Annual Meeting included a presentation by Dr. Jason Efstathiou discussing results of the NRG Oncology/RTOG 0926 trial. This trial assessed selective bladder preserving treatment by radiation therapy concurrent with radiosensitizing chemotherapy following a thorough restaging TURBT.
Presented by Richard Lee, MD, MBA, Urologist
(UroToday.com) In anticipation of the 2021 American Urological Association (AUA) Annual Meeting which is being held, in a delayed fashion, in September, the AUA hosted a “May Kick-Off Weekend” which highlighted a variety of important topics in both benign urology and urologic oncology. Saturday afternoon, Adam Feldman led a course entitled “Trimodality Therapy (TMT) for Management of Muscle Invasive Bladder Cancer” along with faculty Richard Lee and Jason Efstathiou.
Presented by Adam Feldman, MD, MPH, Urologist
(UroToday.com) In anticipation of the 2021 American Urological Association Annual Meeting which is being held, in a delayed fashion, in September, the AUA hosted a “May Kick-Off Weekend” which highlighted a variety of important topics in both benign urology and urologic oncology. Saturday afternoon, Adam Feldman led a course entitled “Trimodality Therapy for Management of Muscle Invasive Bladder Cancer” along with faculty Richard Lee and Jason Efstathiou.
Presented by Adam Feldman, MD, MPH, Urologist
(UroToday.com) In anticipation of the 2021 American Urological Association (AUA) Annual Meeting which is being held, in a delayed fashion, in September, the AUA hosted a “May Kick-Off Weekend” which highlighted a variety of important topics in both benign urology and urologic oncology. Saturday afternoon, Adam Feldman led a course entitled “Trimodality Therapy (TMT) for Management of Muscle Invasive Bladder Cancer” along with faculty Richard Lee and Jason Efstathiou.
Presented by Jason Efstathiou, MD, DPhil
(UroToday.com) In anticipation of the 2021 American Urological Association (AUA) Annual Meeting which is being held, in a delayed fashion, in September, the AUA hosted a “May Kick-Off Weekend” which highlighted a variety of important topics in both benign urology and urologic oncology. Saturday afternoon, Adam Feldman led a course entitled “Trimodality Therapy (TMT) for Management of Muscle Invasive Bladder Cancer” along with faculty Richard Lee and Jason Efstathiou.
Presented by Jason Efstathiou, MD, DPhil
(UroToday.com) In anticipation of the 2021 American Urological Association (AUA) Annual Meeting which is being held, in a delayed fashion, in September, the AUA hosted a “May Kick-Off Weekend” which highlighted a variety of important topics in both benign urology and urologic oncology. Saturday afternoon, Adam Feldman led a course entitled “Trimodality Therapy (TMT) for Management of Muscle Invasive Bladder Cancer” along with faculty Richard Lee and Jason Efstathiou.
Presented by Robert A. Huddart
Toronto, Ontario (UroToday.com) In this discussion, the topic of bladder preservation was presented by Dr. Huddart from the Royal Marsden NHS Foundation Trust in the United Kingdom. Muscle invasive bladder cancer, after diagnosis using TURBT, is usually treated with radical cystectomy with the option of neoadjuvant chemotherapy before surgery.