Bogdana Schmidt, MD, MPH, is an assistant professor in the Division of Urology at the University of Utah Huntsman Cancer Institute in Salt Lake City.

Bogdana Schmidt, MD, MPH, discusses the role of minimally invasive and robotic strategies for the treatment of patients with bladder cancer.

Dr Schmidt on the Role of Minimally Invasive and Robotic Modalities in Bladder Cancer

“Right now, with robotic cystectomy, there was a randomized trial published a couple of years ago that demonstrated an improvement in overall survival for patients who get a robotic cystectomy, and this was based on a decreased risk of death.”

Bogdana Schmidt, MD, MPH, an assistant professor in the Division of Urology at the University of Utah Huntsman Cancer Institute, discussed the role of minimally invasive and robotic modalities in patients with bladder cancer.

The utilization of minimally invasive and robotic-assisted surgeries has initiated a shift in the bladder cancer treatment paradigm, notably because it leads to a faster postsurgical recovery vs traditional surgery, Schmidt began. Past studies have even demonstrated an improvement in overall survival (OS) for patients who received robotic cystectomies for bladder cancer, she explained. Additionally, she noted that this improvement in OS was based on a decreased risk of death associated with blood clots, likely because patients can move around more independently following robotic surgery vs traditional surgery.

Furthermore, the phase 3 SWOG S1011 trial (NCT01224665) evaluated extended lymphadenectomies compared with standard lymphadenectomies in patients with localized muscle-invasive bladder cancer undergoing radical cystectomy, Schmidt continued. Historically, extended lymphadenectomies were performed after retrospective data established that this was the most beneficial modality, she explained. However, she emphasized that the phase 3 study changed the narrative and demonstrated that a standard lymphadenectomy was superior to extended lymphadenectomies because it was associated with less morbidity regarding blood clots. With studies such as this one, identifying and learning more about surgical strategies is essential, particularly as it relates to changing practice, Schmidt concluded.

Of note, the SWOG S1011 study randomly assigned patients 1:1 to undergo extended lymphadenectomy (n = 292) or standard lymphadenectomy (n = 300). At a median follow-up of 6.1 years, 45% vs 42% of patients from the extended lymphadenectomy and standard lymphadenectomy groups had experienced recurrence or death, respectively. At 5 years, the OS rates were 59% vs 63% in the respective groups (HR, 1.13; 95% CI, 0.88-1.45).

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Bogdana Schmidt, MD, MPH, details the emergence of novel treatment delivery methods in bladder cancer.  

Dr Schmidt on the Development of Novel Treatment Delivery Approaches in Bladder Cancer

“TAR-200 utilizes gemcitabine, which is an old, familiar drug, but [TAR-200] delivers it in a very different way. UGN-102 uses mitomycin—also an old, familiar drug—but delivers it in this reverse hydrogel formulation where it stays in the bladder and has a longer sustained delivery… The new delivery mechanisms are fascinating, and I think that's only going to improve how we treat our patients.”

Bogdana Schmidt, MD, MPH, an assistant professor in the Division of Urology at the University of Utah Huntsman Cancer Institute, detailed the development of novel treatment delivery modalities in patients with bladder cancer.

Of significance, novel treatment delivery systems currently under evaluation, such as TAR-200 and UGN-102, represent a shift in the bladder cancer paradigm by providing a touch of innovation, Schmidt began. She explained that TAR-200 still utilizes gemcitabine—a familiar drug in the oncology space—that is delivered in a novel format. Similarly, UGN-102 delivers mitomycin (Mitosol) with a new approach, in which it is administered as a reverse hydrogel formulation and remains in the bladder for sustained exposure, she said.

Regarding other developments in treatment delivery, Schmidt noted that there has been recent progress in utilizing MRI for staging, although this strategy has not yet been commonly adopted. However, she emphasized that although many treatment strategies are on the rise in the bladder cancer space, there are still challenges and current limitations. For example, evaluating areas to identify separate markers for bladder cancer has not been as advanced as the prostate cancer space, for example, with prostate-specific antigen and prostate-specific membrane antigen, she added.

Nevertheless, there are still other approaches that can add to treatment strategies, Schmidt continued. The use of artificial intelligence (AI) can help in enhancing pathology in bladder cancer, she said. If a patient has markers based on pathology signatures, the tool can help predict responses to various treatments, she explained. As an example, she noted that there is a company that can assess pathology slides to predict whether the patient’s tumor is most likely to respond to different treatments, such as an immune-mediated pathway, BCG, or chemotherapeutic pathways, including docetaxel and/or gemcitabine. AI tools like this are becoming more commercially available and more are in development, which are going to continue improving, Schmidt concluded.

Bogdana Schmidt, MD, MPH, highlights FDA approved bladder-sparing therapies for patients with BCG-refractory non–muscle-invasive bladder cancer.

Dr Schmidt on FDA-Approved Bladder-Sparing Therapies in BCG-Refractory NMIBC

“The challenges with [nogapendekin alfa inbakicept], up until very recently, have been the BCG shortage. [This drug requires] coadministration of BCG. If you don’t have BCG, it’s hard to use this drug right now, but they’re working on providing recombinant BCG with it, so I think that’ll increase the uptake of this treatment.”

Bogdana Schmidt, MD, MPH, an assistant professor in the Division of Urology at the University of Utah Huntsman Cancer Institute, highlighted bladder-sparing therapies FDA approved for the treatment of patients with BCG-refractory non–muscle-invasive bladder cancer (NMIBC).

Over the past 5 years, the BCG-refractory NMIBC space has seen 3 FDA approvals, Schmidt began. First, she noted that 

pembrolizumab (Keytruda) was approved in January 2020

 for the treatment of patients with BCG-unresponsive, high-risk NMIBC and carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or elected not to undergo surgery. With a role in the treatment paradigm for a variety of solid tumors, pembrolizumab is a familiar treatment among providers, she said. Pembrolizumab demonstrated initial promise, specifically in patients with intense urinary symptoms who would not benefit from intravesical treatments, she explained. Nevertheless, she emphasized that the associated systemic adverse effects need to be carefully considered in this patient population. Although it’s a great option to have in the treatment armamentarium, it's often not everyone’s first choice, she added.

FDA approved nadofaragene firadenovec-vncg (Adstiladrin)

 for the treatment of patients with high-risk BCG-unresponsive NMIBC and CIS with or without papillary tumors. Notably, it was the first adenoviral vector–based gene therapy approved in this setting, Schmidt explained.

FDA approved nogapendekin alfa inbakicept-pmln (Anktiva) plus BCG

 for the treatment of patients with BCG-unresponsive NMIBC and CIS with or without papillary tumors, she continued. The mechanism of action further stimulates the response to BCG, particularly in this population of patients with BCG-refractoriness, she explained. However, she emphasized that this treatment modality has faced a challenge regarding the recent BCG shortage, especially because BCG is required in combination with nogapendekin alfa inbakicept. Recombinant BCG could soon be an option to help increase the uptake of the treatment, Schmidt concluded.

Bogdana Schmidt

Articles

Dr Schmidt on the Role of Minimally Invasive and Robotic Modalities in Bladder Cancer

Dr Schmidt on the Development of Novel Treatment Delivery Approaches in Bladder Cancer

Dr Schmidt on FDA-Approved Bladder-Sparing Therapies in BCG-Refractory NMIBC