Dr Bochner on the Need for Multimodal Approaches in MIBC

Bernard H. Bochner, MD, FACS, urologic surgeon, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center, discusses the need for a multimodal approach to the management of muscle-invasive bladder cancer (MIBC).

In the management of MIBC, a multimodal approach often includes either preoperative or postoperative treatment regimens, Bochner begins. Historically, the cornerstone of this approach has been platinum-based chemotherapy, which has demonstrated significant benefits in improving outcomes for patients. Studies conducted throughout the 1990s and early 2000s showed that administering platinum-based chemotherapy before bladder removal could improve survival rates by up to one-third for patients with localized, muscle-invasive tumors, he details.

However, a significant unmet need exists regarding patient eligibility for platinum-based chemotherapy, Bochner states. Approximately 40% of patients with MIBC are not candidates for this treatment due to factors such as renal dysfunction, sensory neural hearing loss, or cardiovascular issues. This limitation has driven the search for alternative agents, he says. Additionally, the use of platinum-based chemotherapy in the neoadjuvant setting can lead to overtreatment, as it is difficult to determine which patients have micrometastatic disease or who will be responsive to platinum-based therapy, Bochner adds.

In response to these challenges, there has been considerable interest in evaluating the efficacy of adjuvant chemotherapy as an alternative to neoadjuvant treatment, Bochner says. The rationale is that if adjuvant chemotherapy can offer similar benefits, it might be a viable option for patients who are not eligible for preoperative chemotherapy, he explains. Although studies investigating adjuvant chemotherapy have struggled with accrual over time, meta-analyses suggest that it may indeed offer comparable benefits, Bochner adds. However, the evidence supporting adjuvant chemotherapy is less robust, with studies being relatively small in scale. Furthermore, like neoadjuvant chemotherapy, adjuvant chemotherapy requires that patients be platinum-eligible, he notes.

Overall, the exploration of both neoadjuvant and adjuvant chemotherapy continues to be crucial in the quest to optimize treatment for MIBC, particularly in light of the limitations associated with platinum-based therapies and the need for alternative strategies that can accommodate a broader patient population, Bochner concludes.

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Bernard H. Bochner, MD, FACS discusses genomic complexity and heterogeneity in bladder cancer tumors.

Bernard H. Bochner, MD, FACS, urologic surgeon, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center, discusses the genomic complexity and heterogeneity of bladder cancer and what this heterogeneity has meant for the exploration of treatment options for this patient population.

Due to a substantial amount of research investigating the heterogeneity of bladder cancer, it has been established that patients with bladder cancer can present with tumors that harbor a wide variety of genetic abnormalities, Bochner begins, noting that these findings have created opportunities to explore different treatment strategies. He explains that bladder cancer is associated with a high tumor mutational burden (TMB), which has been linked with a more favorable responses to checkpoint inhibitors across different tumor types.

Clinical studies in the bladder cancer realm have explored the use of checkpoint inhibitors in combination with chemotherapy in the neoadjuvant setting for patients with platinum-eligible and -ineligible disease. The primary objective of exploring neoadjuvant checkpoint inhibition in combination with chemotherapy has been to increase the rate of patients who experience tumor downstaging or complete pathologic responses, and results from these studies have shown that checkpoint inhibitors have activity in the preoperative setting for patients with bladder cancer.

Bochner notes that this approach reflects a broader trend in oncology toward leveraging the unique genetic profiles of tumors to tailor and enhance treatment efficacy. By understanding the specific genetic characteristics of bladder cancer, including its high TMB, oncologists can better strategize therapies that are more likely to result in improved patient outcomes, he explains

Bochner's insights underscore the importance of genetic profiling in identifying suitable candidates for checkpoint inhibition and other targeted therapies in bladder cancer. This shift towards personalized medicine continues to shape the landscape of cancer treatment, promising a more nuanced and effective approach to managing a disease as complex and variable as bladder cancer.

Dr Bochner on Genetic Heterogeneity in Bladder Cancer

Dr Bochner on Bladder-Sparing Regimens in MIBC

Bernard H. Bochner, MD, FACS, urologic surgeon, Memorial Sloan Kettering Cancer Center, 

 evaluating the feasibility and safety of potential bladder-sparing options for patients with muscle-invasive bladder cancer (MIBC).

In an interview with At the 17th Annual Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies, an event hosted by Physician’s Education Resource (PER®), Bochner highlighted the significance of ongoing investigations of MIBC management strategies, including the phase 2 Alliance A031701 trial (NCT03609216), which is being spearheaded by Gopa Iyer, MD, from Memorial Sloan Kettering Cancer Center. 

The trial was designed to evaluate the efficacy of chemotherapy alone in patients with MIBC with bladder preservation whose tumors harbor DNA damage repair (DDR) mutations. Prospective data have shown that many of these genes exhibit a strong correlation with platinum sensitivity, which is adeterminant of complete response (CR), Bochner expands. Through genetic sequencing of tumors, eligible mutations that could potentially guide the administration of platinum-based chemotherapy will be identified, he states. Eligible patients will be treated with investigator’s choice of standard dose or dose dense gemcitabine and cisplatin chemotherapy, with simultaneously genetic sequencing of pretreatment transurethral resection tumor specimens. Patients displaying 1 of 9 deleterious DDR alterations who exhibit a clinical CR following treatment with chemotherapy will be considered eligiblefor bladder preservation on a trial basis to identify the safety of this approach, he reports.

Scrutinizing molecular signatures could help identify subsets of patients for whom bladder preservation may be a viable option without compromising long-term outcomes, Bochner shares. Endeavors such as the Alliance A031701 trial epitomize the strides being made in personalized medicine, Bochner explains. The trial exemplifies a paradigm shift in the management of MIBC, potentially allowing for a more refined and patient-centric approach to treatment decision-making in this disease space, he concludes.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing

referapatient@mskcc.org, or by calling 833-315-2722.

Bernard H. Bochner, MD, FACS, discusses ongoing studies evaluating the potential bladder-sparing options for patients with muscle-invasive bladder cancer.

Bernard H. Bochner, MD, FACS, discusses considerations for community when treating patients with muscle-invasive bladder cancer 

Dr Bochner on Key Points for Community Oncologists in the Management of Muscle-Invasive Bladder Cancer

Bernard H. Bochner, MD, FACS, urologic surgeon, Memorial Sloan Kettering Cancer Center, discusses considerations clinicians practicing in the community setting should be aware of when treating patients with muscle-invasive bladder cancer (MIBC).

Approximately 60% of patients with MIBC are candidates for treatment with a platinum-based regimen, including gemcitabine, cisplatin, and/or methotrexate, vinblastine sulfate, doxorubicin hydrochloride (Adriamycin), and cisplatin (MVAC), with healthier patients being pushed towards dose-dense regimens, Bochner begins. However, there is a significant subset of patients who will not be eligible for platinum-based treatment due to comorbidities, Bochner continues. In this setting, several large randomized clinical trials are underway aiming to identify the best course of treatment for these patients, Bochner says.

Studies are evaluating checkpoint inhibitor monotherapy, dual checkpoint inhibitor combinations, and combinations with antibody-drug conjugates and checkpoint inhibitors, with the ultimate goal of increasing the number of patients who can be down staged, Bochner notes.

Ongoing studies in the neoadjuvant setting include the phase 2 ABATE study (NCT04289779) of atezolizumab (Tecentriq) with cabozantinib (Cabometyx), the phase 3 KEYNOTE-866 trial (NCT03924856) of gemcitabine plus cisplatin with or without perioperative pembrolizumab (Keytruda), and the phase 3 KEYNOTE-905 study (NCT03924895) of pembrolizumab with or without enfortumab vedotin-ejfv (Padcev).

In the adjuvant setting, there are several available options, Bochner continues. Although overall survival data with these regimens are not yet mature, the risk of recurrence is decreased by approximately 30% or more with these regimens, especially in patients with PD-L1–positive disease, Bochner notes. Patients with previously treated disease who have invasive disease following surgery are at a high risk of recurrence, as are patients with extravesical disease who did not previously receive chemotherapy, Bochner says. As such, it’s imperative to relay to patients that, based on high level evidence, a year of checkpoint inhibitor therapy may significantly improve their outcomes, Bochner concludes.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

Bernard H. Bochner, MD, FACS, discusses considerations for community oncologists when treating patients with muscle-invasive bladder cancer.

Bernard H. Bochner, MD, FACS, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center (MSKCC), discusses the potential standardization of molecular profiling in bladder cancer.

The utility of molecular profiling is in its infancy, says Bochner. However, testing has the potential to impact treatment options for many patients.

For example, molecular profiling may provide insight on potentially targetable mutations in patients who do not respond to standard treatment like intravesical therapy or those with metastatic disease who progress through first- and second-line therapy.

At MSKCC, molecular profiling is commonly used to obtain data regarding how a patient’s genomicmakeup can enhance treatment, explains Bochner. Though standardization is not ready for primetime, molecular profiling may become commonplace in the future.

Bernard H. Bochner, MD, FACS, discusses the potential standardization of molecular profiling in bladder cancer.

Dr. Bochner on Standardizing Molecular Profiling in Bladder Cancer

Bernard H. Bochner, MD, FACS, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center, discusses future treatment strategies in early-stage nonmuscle—invasive bladder cancer (NMIBC).

It is important to understand that there are a variety of risk groups to categorize patients with NMIBC, Bochner says. High-risk patients are unresponsive to Bacillus Calmette-Guérin intravesical immunotherapy. These patients should be referred to medical oncologists because checkpoint inhibitors are starting to make headway in that space.

Moreover, it is important to treat these patients aggressively because NMIBC tends to progress to muscle-invasive disease or present with local metastases if therapy is delayed. In the near future, urologists and medical oncologists are going to work closely to understand the biology of bladder cancer in order to integrate new systemic therapies like PD-1/PD-L1 inhibitors, Bochner predicts.

Bernard H. Bochner, MD, FACS, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center, discusses future treatment strategies in early-stage non–muscle invasive bladder cancer.

Dr. Bochner on Future Treatment Strategies in Early-Stage NMIBC

Bernard H. Bochner, MD, FACS, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center, discusses promising targets and pathways in bladder cancer.

Immunotherapy has shown a lot of promise in bladder cancer, Bochner says. This is likely related to the high tumor mutational burden (TMB) associated with bladder cancers. In other immunogenic tumors such as lung cancer and melanoma, TMB is also considerably high. With immunotherapy, physicians are able to exploit the DNA damage repair pathway. Currently, there are 7 FDA-approved checkpoint inhibitors in bladder cancer, 5 of which are approved as second-line treatment for platinum-refractory patients, and 2 of which are approved as frontline treatment for platinum-ineligible patients.

Next-generation sequencing tests have also identified cell growth and signaling pathways that may be useful in the future. From a molecular standpoint, it is important to remember that bladder cancer is not 1 disease but a multitude of different subtypes. It is a ripe field for investigation, in which there is plenty of room for progress, Bochner concludes.

Bernard H. Bochner, MD, FACS, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center, discusses promising targets and pathways in the treatment of patients with bladder cancer.

Dr. Bochner on Promising Targets and Pathways in Bladder Cancer

Bernard H. Bochner, MD, FACS, Sir Murray F. Brennan Chair in Surgery, Memorial Sloan Kettering Cancer Center, discusses the importance of molecular profiling in the treatment of patients with bladder cancer.

We are learning a tremendous amount about the biology of bladder cancer, Bochner says, in large part due to the advanced technology and availability of genetic testing. Importantly, bladder cancer is not 1 disease but a number of heterogeneous subtypes that can be targeted with individualized therapy. As such, the field is ripe for genetic testing that will allow for the identification of additional pathways and alterations that had not previously been considered.

There is also the need for additional biomarkers to provide prognostic and predictive value. As new therapies are developed, it is important to understand which patients will benefit and which patients will become resistant. Moreover, it is critical to identify patients who are at high risk of developing advanced disease after local therapy so that they can receive combination treatment upfront. On the other hand, patients who have a good outcome with local therapy may be able to avoid the need for systemic therapy, Bochner says.

Bernard H. Bochner, MD, FACS, chair of surgery, Memorial Sloan Kettering Cancer Center, discusses the importance of molecular profiling in the treatment of patients with bladder cancer.

Bernard H. Bochner, MD, FACS

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