Gary D. Steinberg, MD, director, Urologic Oncology, The University of Chicago Medicine, discusses the standard of care in patients with non-muscle invasive bladder cancer (NMIBC).

Bacillus Calmette-Guérin (BCG) is the current frontline standard for patients who are diagnosed with NMIBC, especially those with high-risk or high-grade disease, says Steinberg. Based on accumulated data sets, less than half of patients who should be receiving intravesical BCG actually are. Approximately 30% to 40% of patients with high-risk disease who receive BCG will progress to recurrent high-grade bladder cancer or develop progressive muscle-invasive bladder cancer.

Although the intravesical immunotherapy has been around since the 1980s, it remains an underutilized approach, says Steinberg. This may be a result of a lack of adherence to current guidelines, he adds. In 2015, the American Urology Association released new guidelines for patients with NMIBC which clearly outline how to diagnose, treat, and survey the disease—revisions of which Steinberg hopes are more commonly utilized moving forward.

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Dr. Steinberg on the Standard of Care in Non-Muscle Invasive Bladder Cancer

Gary D. Steinberg, MD, director, Urologic Oncology, The University of Chicago Medicine, discusses treatment approaches in non-muscle invasive bladder cancer (NMIBC).

In high-risk NMIBC, many therapies are directly inserted into the bladder. However, Steinberg says intravesical chemotherapy may not be the best means of delivering treatment to patients. There are, however, many trials that are examining better ways of delivering intravesical chemotherapy.

The future will likely rely on more novel mechanisms, such as oncolytic vaccines alone and oncolytic vaccines in combination with checkpoint inhibitors, says Steinberg. One vaccine that is currently being tested is INO-5401, which is a combination of multiple different antigens. It is an injectable DNA vaccine that targets WT1, HTERT, and PSMA. It is also combined with an immune-stimulatory molecule, IL-12, to enable the immune system to recognize these antigens and target the cancer. Studies have shown that DNA vaccines are generally well tolerated and safe.

Dr. Steinberg on Treatment Approaches in Non-Muscle Invasive Bladder Cancer

Gary D. Steinberg, MD, director, Urologic Oncology, The University of Chicago Medicine, discusses the management of patients with prostate cancer.

Physicians have access to a variety of novel agents in the management of prostate cancer, especially in metastatic prostate cancer, notes Steinberg. In February 2018, the FDA approved abiraterone acetate (Zytiga) for use in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer. The approval was based on the phase III LATITUDE study, showing a 38% reduction in the risk of death with the addition of abiraterone and prednisone to androgen-deprivation therapy (ADT) compared with ADT alone.

The field is also moving very rapidly towards understanding the genetics of the disease. The use of various modalities is allowing physicians to risk stratify patients more effectively, adds Steinberg. This ensures that patients who do not need treatment will not be treated and those who need treatment will be treated. Additionally, physicians are trying to determine the best test beyond the prostate-specific antigen serum test to identify genetic markers that predict a cancer’s aggressiveness.

Dr. Steinberg on the Management of Prostate Cancer

Gary D. Steinberg, MD, director, Urologic Oncology, The University of Chicago Medicine, discusses bacillus Calmette-Guérin (BCG) progression in non-muscle invasive bladder cancer (NMIBC).

BCG is a form of immunotherapy that is traditionally used in patients with NMIBC. However, one of the problems with high-risk and high-grade NMIBC is that it is not one disease, explains Steinberg, but rather a heterogenous malignancy. There are notable differences in recurrence rates and progression rates that necessitate investigation into whether it is a multifocal tumor, the size, whether or not there is lymphatic or vascular evasion, and the response to intravesical BCG. Additionally, the timing of response to BCG.

There are many factors that physicians have to take into account to help predict which patients are going to progress on BCG. This may be augmented by the identification of biomarkers of response as well as biomarkers of aggressiveness, adds Steinberg.

Dr. Steinberg on BCG Progression in Non-Muscle Invasive Bladder Cancer

Gary Steinberg, MD, director, Urologic Oncology, The University of Chicago Medicine, discusses the immune response results of vesigenurtacel-I (HS-410) vaccine in non-muscle invasive bladder cancer (NMIBC).

In this phase II randomized trial, patients who were either BCG-naïve or recurrent with or without carcinoma in situ (CIS) received 1 of 2 doses of HS-410 (either 106 or 107cells/dose) or placebo. This was in combination with 6 weeks of induction BCG, followed by HS-410 for 6 more weeks.

HS-410 is compromised of an allogeneic cell line which is selected for high expression from bladder tumor antigens. It was found to be well tolerated and immunologic responses are consistent.

According to Steinberg, this vaccine shows promise as a potential treatment for NMIBC.

Dr. Steinberg on Trial of HS-410 Vaccine in Bladder Cancer

Gary D. Steinberg, MD, Bruce and Beth White family professor, professor of surgery, director, urologic oncology, University of Chicago Medicine, discusses new guidelines for for the management of non-muscle invasive bladder cancer (NMIBC) from the American Urological Association (AUA) and the Society of Urological Oncology (SUO).

The new guidelines were created from a compilation of all of the latest literature and the input of many experts in the field, says Steinberg. The guidelines include information concerning diagnosis, risk stratification, variant histologies, urine markers after diagnosis, intravesical therapy, BCG relapse and salvage regimens, TURBT/repeat resection, role of cystectomy, and risk adjusted surveillance and follow-up strategies.

The guidelines are succinct and straight-forward providing oncologists with a much better understanding as to how patients should  be managed and treated.

Dr. Gary Steinberg on New AUA Guidelines for Bladder Cancer

Gary D. Steinberg, MD, Bruce and Beth White Family Professor, professor of Surgery, director of Urologic Oncology, University of Chicago Medicine, discusses the FDA approval of atezolizumab (Tecentriq) as a treatment for patients with with locally advanced or metastatic urothelial carcinoma (mUC) whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery.

The accelerated approval was based on data from the phase II IMvigor 210 study, in which atezolizumab demonstrated an overall response rate (ORR) of 14.8% in patients with locally advanced or mUC. This was regardless of PD-L1 expression. Among patients with PD-L1 expression ≥5%, ORR was 26%. The PD-L1 assay Ventana PD-L1 (SP142) was concurrently approved as a companion diagnostic.

Atezolizumab's approval is a game-changer for the treatment landscape of the disease, Steinberg explains.

Gary D. Steinberg, MD

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