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Immunotherapy Shows Promise in Reducing Urothelial Cancer Mortality

October 2017

Urothelial cancer is the fifth most common cancer in the United States, with 82,660 new cases of bladder, ureter, and urinary organ cancers estimated for 2017. Bladder cancer represents an estimated 79,030 of these cases and is expected to cause 16,879 deaths in the United States in 2017.1 About 20% to 25% of newly diagnosed cases are muscle invasive, and about the same percentage of those with high-risk cancer progress to muscle-invasive disease over time, regardless of treatments.2 Bladder cancer mortality has remained stable for the past 3 decades, but new drugs and therapeutic regimens, including immunotherapy, may improve care and reduce mortality.1, 3

Disease management requires a team approach. Imaging—which can employ positron emission tomography, computed tomography, and magnetic resonance imaging—and pathologic examination of cancers assist clinical staging and monitoring of invasive disease. For patients with muscle-invasive disease, cystectomy is the main treatment. Platinum-based combination chemotherapy is currently the standard of care for first-line treatment of advanced or metastatic disease.2, 3 Bladder-sparing treatments combining surgery, chemotherapy, and radiotherapy have improved survival.4, 5 Although intravesical immunotherapy has been used for non-muscle-invasive disease, currently checkpoint inhibitors represent the only approved systemic immunotherapy for advanced disease.3, 5 No consensus exists for second-line therapy in patients who do not respond to chemotherapy. New options include other chemotherapeutic agents and immunotherapy with checkpoint inhibitors.

Consult-Cancer-Care-GI-October-2017-Feature-Article-Main-Image
— Chemotherapy is the first-line treatment for advanced urothelial cancer. Immunotherapy, however, is emerging as a new second-line therapy option.

Checkpoint inhibitors target some of the checks and balances built into the immune system that are exploited by cancer cells. These include receptors for cytotoxic T-lymphocyte antigen 4, programmed death-1 (PD-1) and their ligand (PD-L1).4 Cancer cells express PD-L1 and avoid attack by the immune system. Checkpoint inhibitors block this inhibitory response and thus permit immune system action against cancer cells, shrinking or slowing tumor growth. Currently, 5 such drugs (nivolumab, atezolizumab, pembrolizumab, durvalumab and avelumab) have been approved and successfully used in patients with bladder cancer. Therapy focuses on determining the best drug and treatment regimen for the particular patient.4, 5

University of Minnesota Health physicians participate in several clinical trials testing the use of checkpoint inhibitors. Physicians are examining whether adjuvant or neoadjuvant use of the therapies can improve survival of patients with metastatic disease as well as early stage disease. One multicenter, phase II trial will evaluate the efficacy of neoadjuvant nivolumab with cisplatin and gemcitabine in patients who have muscle-invasive bladder cancer and are undergoing radical cystectomy. A currently enrolling phase III trial will test a gene-based therapy in patients with non-muscle-invasive bladder cancer. In earlier trials, this therapy was shown to improve treatment delivery and prolong exposure of cancer cells to interferon-alfa2b.6 Additional trials seek to identify markers of bladder cancer progression with the goal of better delineating disease risk and therapeutic targets.7

References

  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30.
  2. Krishna SR, Konety BR. Current concepts in the management of muscle invasive bladder cancer. Indian J Surg Oncol. 2017;8(1):74-81.
  3. Gupta S, Gill D, Poole A, Agarwal N. Systematic immunotherapy for urothelial cancer: current trends and future directions. Cancers (Basel). 2017;9(2):pii: E15 DOI: 3390/cancers9020015.
  4. Popovic LS, Matovina-Brko G, Popovic M. Checkpoint inhibitors in the treatment of urological malignancies. EMSO Open. 2017;2(2): e000165.
  5. Lobo N, Mount C, Omar K, Nair R, Thurairaja R, Khan MS. Landmarks in the treatment of muscle-invasive bladder cancer. Nat Rev Urol. 2017. Epub ahead of print. DOI:1038/nrurol 2017.82
  6. A Study to Evaluate INSTILADRIN® in Patients with High-Grade, Bacillus Calmette-Guerin (BCG) Unresponsive NMIBC. NCT01687249. Clinicaltrials.gov. Accessed Sept. 7, 2017.
  7. Isharwal S, Konety B. Non-muscle invasive bladder cancer risk stratification. Indian J Urol. 2015;31(4):289-296.

When to refer

The urology, radiation, and oncology teams with University of Minnesota Health Cancer Care offer comprehensive diagnosis and treatment of genitourinary (GU) cancers. Our care team is recognized nationally and internationally for its leadership in research into treating these cancers, and our Institute for Prostate and Urologic Cancers focuses on providing advanced, team-based, and individually tailored care for patients with bladder cancer and other common GU cancers.

Our multidisciplinary teams work together to marshal the best resources and care for patients. Treatment regimens are tailored to the individual patient and include the latest surgical approaches, radiation therapy, and chemo- and immunotherapy, among treatment options. Registered dietitians and specialists in palliative care support patients through treatment. Our physicians also offer access to clinical trials that test new immunologic agents and regimens for patients with advanced or recurrent disease.

Our teams work hard to keep physicians informed of patients’ care and provide detailed reports, from diagnosis to treatment and follow-up. Patients and family members may find help through our Peer-to-Peer Program and Bladder Cancer Support Group.

To find current clinical trials available through M Health providers: studyfinder.umn.edu.

Physician Outreach Program

The Cancer Care Outreach Program is designed to provide education and facilitate knowledge sharing between our team and the medical community.

To schedule a physician meeting or to visit our facility, contact Melinda Tuma, System Manager, Outreach Services. Phone: 612-273-9947; email: marvold1@fairview.org.

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