Neil Desai, MD, MHS, associate professor, director, Clinical Research, Department of Radiation Oncology, Dedman Family Scholar in Clinical Care, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the potential benefits and limitations of utilizing chemoradiation or triple modality therapy for bladder preservation in the upfront management of patients with locally advanced, nonmetastatic muscle-invasive bladder cancer (MIBC).

Determining whether bladder preservation is the optimal management strategy for patients with locally advanced, nonmetastatic MIBC can be challenging, especially when considering a patient's comorbidities and the extent of disease beyond the bladder, Desai begins. Accordingly, the decision to pursue bladder preservation in place of radical cystectomy necessitates a thorough discussion with patients concerning the importance of quality of life and the risks associated with this procedure.

 State of the Science Summit™, Desai expanded on a case study of locally advanced bladder cancer invading the cervix of a woman with comorbid renal dysfunction.

In this unconventional case, the patient had both a high risk of distant relapse and high comorbidity-related morbidity and mortality, Desai details. These conflicting priorities complicated the decision-making process, he explained.

Reserarch suggests that the standard management approach of cisplatin-based chemotherapy prior to cystectomy might not be suitable for patients who can tolerate neoadjuvant gemcitabine–and carboplatin-based chemotherapy despite their comorbidities, Desai reports. However, the patient had cervical cancer and cervical invasion in addition to bladder cancer. This feature indicates that the patient is a less optimal candidate for bladder preservation due to the challenges in monitoring outcomes when disease extends beyond the bladder, Desai says.

Ultimately, chemoradiation should be considered a reasonable initial therapy option for this patient, with the acknowledgment of potentially higher failure rates and increased morbidity compared with more localized cases, Desai states. The limitations of relying solely on imaging and cystoscopy for surveillance when disease involves areas beyond the bladder were also recognized, he adds. Overall this case study reinforces the importance of balancing the need for definitive treatment, which can alleviate local morbidity and reduce overall mortality risk, with the patient's ability to tolerate therapy, Desai concludes.

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Neil Desai, MD, discusses the potential benefits and limitations of utilizing chemoradiation or triple modality therapy for bladder preservation in the upfront management of patients with locally advanced, nonmetastatic muscle-invasive bladder cancer.

Dr Desai on the Benefits and Limitations of Bladder Preservation With Chemoradiation in MIBC

Neil Desai, MD, associate professor, radiation oncology, UT Southwestern Harold C. Simmons Comprehensive Cancer Center, discusses the investigation of immune checkpoint inhibitors with chemoradiation in urothelial cancer.

Patients with urothelial cancer have the risk of experiencing distant metastases and disease progression, and ongoing clinical trials are focusing on addressing these unmet needs with alternative approaches beyond radiation and chemotherapy, Desai explains. Various studies are exploring the addition of immune checkpoint inhibitors to chemoradiation, Desai adds, including the phase 3 SWOG 1806 trial (NCT03775265) investigating the addition of atezolizumab (Tecentriq) to standard chemoradiotherapy, Desai says.

Beneficial data have been observed in high-risk patients with urothelial cancer who received an adjuvant checkpoint inhibitor following cystectomy, Desai continues. Checkpoint inhibitors can address the risk of distant metastases in patients with urothelial cancer and potentially provide a survival benefit for these patients, Desai concludes.

Neil Desai, MD, discusses the investigation of immune checkpoint inhibitors with chemoradiation in urothelial cancer.


Dr. Desai on Immune Checkpoint Inhibitors with Chemoradiation in Urothelial Cancer

Neil Desai, MD, associate professor, radiation oncology, UT Southwestern Harold C. Simmons Comprehensive Cancer Center, discusses the ideal patient for bladder preservation in urothelial cancer.

There have been a substantial amount of research examining selection criteria for the ideal patient for bladder preservation, Desai says. These criteria include a smaller tumor size, the ability for surgeons to completely resect a tumor, the ability for patients to receive standard chemotherapy with concurrent radiation, and a lack of hydronephrosis, Desai explains.

When patients don’t meet some aspects of the selection criteria, it means they have a higher burden of disease, and bladder preservation may not provide as durable of control in patients with higher disease burden, Desai continues. It is important to differentiate selection criteria from eligibility, as patients not meeting the selection criteria could still be eligible for bladder preservation; rather, these patients have a higher risk of disease progression following preservation, Desai concludes.

Neil Desai, MD, discusses the ideal patient for bladder preservation in urothelial cancer.


Dr. Desai on the Ideal Patient for Bladder Preservation in Urothelial Cancer

Neil Desai, MD, associate professor, radiation oncology, UT Southwestern Harold C. Simmons Comprehensive Cancer Center, discusses the evolving standard of care in urothelial cancer.

The standard of care for muscle-invasive bladder cancer of urothelial origin has long been neoadjuvant cisplatin-based chemotherapy followed by a radical cystectomy, Desai explains. However, this treatment course is not the best option for all patients, Desai adds. Some patients with bladder cancer often have comorbidities, and given the difficult nature of a cystectomy, not all patients will be candidates, Desai adds.

The goal for all of these patients is to preserve the bladder and quality of life, and researchers are continuing to explore alternatives for patients who are not ideal candidates for cystectomy, Desai concludes.

Neil Desai, MD, discusses the evolving standard of care in urothelial cancer.


Dr. Desai on the Evolving Standard of Care in Urothelial Cancer

Neil Desai, MD, associate professor, radiation oncology, UT Southwestern Harold C. Simmons Comprehensive Cancer Center, discusses the variety of options available for patients with localized urothelial cancer who are ineligible for cisplatin-based chemoradiation.

Although cisplatin-based chemoradiation therapies such as those studied in the RTOG trials have been proven effective in many patients with urothelial cancer who are considering bladder preservation, they are not an option for elderly patients, patients with comorbidities such as renal issues, or those who are cisplatin ineligible for other reasons, Desai explains. Instead, regimens such as 5-FU and mitomycin C, which are highly effective in the cisplatin-ineligible population, can be used, Desai notes. Gemcitabine plus radiation administered in shorter-course and longer-course radiation schedules is also effective and feasible to use in patients who may not be eligible for other therapies, Desai adds.

The majority of patients with localized bladder cancer are eligible for some form of radiosensitizing chemotherapy, Desai says. In the future, immunotherapy will play an increasingly larger role in urothelial disease, such as in the adjuvant setting with the goal of bladder preservation, Desai concludes.

Neil Desai, MD, discusses the variety of options available for patients with localized urothelial cancer who are ineligible for cisplatin-based chemoradiation.

Neil Desai, MD

Articles

Dr Desai on the Benefits and Limitations of Bladder Preservation With Chemoradiation in MIBC

Dr. Desai on Immune Checkpoint Inhibitors with Chemoradiation in Urothelial Cancer

Dr. Desai on the Ideal Patient for Bladder Preservation in Urothelial Cancer

Dr. Desai on the Evolving Standard of Care in Urothelial Cancer

Dr. Desai on Expanding Options for Cisplatin-Ineligible Bladder Cancer