For Your Patients: Immunotherapy Increasingly Important for Muscle-Invasive Bladder Cancer

— What it means and how to know if it's an option

Illustration of a syringe injecting medicine over a bladder with urothelial cancer
Key Points

After being diagnosed with muscle-invasive bladder cancer (MIBC), you will likely be evaluated by a multidisciplinary team of a urologist, radiation oncologist, and medical oncologist. They will discuss the risks and benefits of each treatment option, and depending on whether you're considered a candidate for surgery, which standard-of-care options are available for you. Both surgery and radiation can be made more effective by the addition of systemic therapy.

Systemic therapies given prior to surgery are called neoadjuvant, and those given after surgery are termed adjuvant treatments.

If surgery is an option, the standard of care is radical cystectomy -- i.e., removal of the bladder -- preceded by neoadjuvant chemotherapy, which aims to shrink the tumor before surgery and has been proven to prolong survival compared with surgery alone.

Radical cystectomy involves removal of the entire bladder, and typically in men, the prostate and seminal vesicles, and in women, the uterus, ovaries, and fallopian tubes. You will also undergo a procedure called urinary diversion, in which tubes or urine-collecting bags are placed for urine excretion and storage. Cystectomy may be performed through open surgery or minimally invasive (laparoscopic) techniques, if appropriate for you.

No matter the treatment, however, MIBC has a high risk of recurring. About half of patients are deemed ineligible for neoadjuvant chemotherapy and some decline it, usually because of fear of side effects. Patients may be considered for adjuvant systemic options such as chemotherapy, or adjuvant (i.e., given after surgery) immunotherapy. Immunotherapy and chemotherapy are mechanistically different, and their side effect profiles are also distinct.

Adjuvant Immunotherapy: A New Option for MIBC

Nivolumab (Opdivo), an immune checkpoint inhibitor, is now considered a standard of care for select patients with high-risk MIBC after surgery. In initial results from a clinical trial known as CheckMate-274, nivolumab extended the duration of time without the disease returning and reduced the chance of distant cancer spread (metastases) in patients meeting the inclusion criteria.

Specifically, MIBC patients were eligible for adjuvant nivolumab if they did not receive neoadjuvant chemotherapy and were found to have T3 disease after surgery, or for those where despite neoadjuvant chemotherapy there was persistence of muscle-invasive disease. Patients in that trial who received prior neoadjuvant chemotherapy had greater benefit from nivolumab than those who did not, since these patients likely had chemo-resistant disease that was persistent.

Bladder-Preservation Techniques: Trimodal Therapy

Treatments to preserve the bladder may be an alternative to radical cystectomy in certain situations. Bladder preservation can include transurethral resection of the bladder tumor (TURBT), which involves surgery through a cystoscope to remove the tumor and the addition of chemotherapy and radiation therapy, termed trimodality therapy (TMT).

Patient selection is a key part of the possibility of bladder preservation. Appropriate patients for TMT are those who are likely to respond to radiation and can safely tolerate the therapy. Ideally, patients would have a complete TURBT, a single tumor ("unifocal disease"), and good bladder function and capacity.

Newer radiation techniques, such as intensity-modulated radiotherapy and image-guided radiotherapy, can enhance the results and spare normal tissue from the damaging effects of radiation. Patients who opt for TMT must commit to having long-term follow-up with cystoscopy. Your medical oncologist will discuss with you the systemic chemotherapy options while you receive radiation treatments to sensitize your cancer to the effect of radiotherapy.

Ongoing Trials of Neoadjuvant Therapy

Neoadjuvant chemotherapy plus immunotherapy may be effective in patients who are eligible for chemotherapy prior to radical cystectomy. This combination is generally safe and has demonstrated promising rates of response in clinical trials, though this is not currently considered standard of care.

Read previous installments in this series:

For Your Patients: Urothelial Cancer 101

For Your Patients: Staging Urothelial Cancer

For Your Patients: Weighing the Treatment Possibilities for Non-Muscle-Invasive Bladder Cancer

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.