Bladder cancer: What is a survivor?
By Kathleen Hoffman, PhD, MSPH
Bladder cancer is the fourth most common cancer in men. When detected early, it is considered highly treatable.1 In 2021, about 83,000 people were expected to be diagnosed with bladder cancer (64,280 in men and 19,450 in women).2 Ninety percent of these cancers are urothelial carcinomas (UC), or cancers of the lining of the urinary tract. Unfortunately, UC may also recur.
For example, consider that about 50% of all bladder cancers are discovered while the cancer is only in the inner layer of the bladder wall (non-muscular invasive or NMIBC).2 The first treatment for NMIBC is a non-invasive surgery (and diagnostic tool) to remove the tumors called transurethral resection for bladder tumor, or TURBT. A 2018 Phase III study found that flushing the bladders of patients with low grade tumors with the chemotherapy drug gemcitabine after TURBT reduced the rate of recurrence to 35% of the study group versus recurrence in 47% of the placebo group.3
That is, it is a significant improvement when only a third of the patients have the cancer return within four years. It means that 35 of 100 patients will need treatment again even with gemcitabine treatment. That’s for the low-grade cancers.
The five-year survival statistics for the more invasive cases of the disease are discouraging. Only 37% of patients who had their UC diagnosed when it was considered “regional” (spread to nearby lymph nodes or structures) were alive five years later. For those with distant metastases, the rate drops to 6%. There is a great need for advances in treatment for recurrent and advanced bladder cancer.4
I was diagnosed with aggressive form of bladder cancer in the third week of July after several months of ongoing UTI like symptoms…statistically I wasn’t supposed to get this but I did and that too a bad one. We were all shocked and I still cannot comprehend what is happening with me. The cancer had already metastasized to many lymph nodes. [My oncologist]…said if surgery won’t be an option, he would put me on Immunotherapy. All these words are new to me and scare me… I have been feeling hopeful but being on Immunotherapy to me feels like a ticking bomb.
In general, cases are separated based on whether the UC is non-muscle invasive disease (NMIBC) or muscle invasive disease (MIBC). There are also cases where the cancer has not invaded the muscle but is an aggressive cancer, called carcinoma in situ (CIS). Adjuvant treatments may depend on whether a patient is or is not able to tolerate the chemotherapy drug cisplatin. When the cancer has penetrated the muscular wall (Stage 2, 3, or 4), the most widely used surgery is radical cystectomy – complete removal of the patient’s bladder and nearby organs in the pelvis.5
“Radical” is an appropriate term, particularly for patients. The surgery is major, and it requires creating a new path for urine to exit the body – a dramatic and permanent change in quality of life for the patient.
The gating factors in previous treatment decisions have become nuanced. In the past few years, checkpoint immunotherapies have been approved for more advanced bladder cancer. In 2020, Arjun V. Balar, M.D., the director of the genitourinary medical oncology program at NYU Langone Health’s Perlmutter Cancer Center, said:
Several trials have consistently demonstrated that checkpoint inhibitors are active in advanced disease, with response rates ranging from 15 to 30 percent depending on the study and the line of treatment… In muscle-invasive disease, there are ongoing studies looking at the benefits of immunotherapy, either alone or in combination with chemotherapy, prior to cystectomy. There are also trials combining checkpoint immunotherapy with chemoradiation as an alternative to cystectomy, allowing patients to keep their bladder.6
Dr. Balar hopes that combined therapies and novel treatments, including the combination of dual checkpoint immunotherapy targeting the PD-1 and CTLA-4 pathways and antibody drug conjugates such as enfortumab vedotin, will soon make sparing the bladder an option for more patients.
Just in 2021, the FDA approved new immunotherapy drug indications for treating advanced bladder cancer.
First, in July 2021, the FDA granted regular approval for enfortumab vedotin-ejfv, an antibody drug conjugate, for locally advanced or metastatic urothelial cancer in patients who had previously failed to benefit from a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy, or who were ineligible for cisplatin-containing chemotherapy after receiving one or more prior lines of therapy. This expanded treatment option is for patients who had already failed on an immunotherapy treatment and chemo.7
On August 20th, the FDA approved nivolumbab for adjuvant treatment of urothelial carcinoma for patients who are at high risk of recurrence after undergoing radical resection. This was the first FDA approval for adjuvant treatment of patients with high-risk UC.8
Then, on August 31st, the FDA approved using pembrolizumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for any platinum-containing chemotherapy.9 This is an expansion of pembrolizumab’s previous 2020 approval for treating “… patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.”10
The trend is that multi-modal treatments using novel agents and immunotherapies alongside known chemotherapies offer physicians and patients options beyond BCG or cystectomy. The field continues to broaden: As of this writing, there are over 200 clinical trials recruiting patients for studies in urothelial carcinoma.
The search is on for the combinations of checkpoint inhibitors and targeted treatments that will be most effective. Further studies may reveal which biomarkers are predictive of treatment lines for a given subgroup of patients. As one Inspire member said:
Surgery and chemo did not work for me, but immunotherapy did! I had been put on passive care at that point because they did not expect the immunotherapy to work. Surprise! My advise, only worry about your next appointment and making certain you have all your questions on a list. This road called bladder ca is full of turns and twists. Don’t waste your precious time worrying about stuff that might never be. Spend your time making good decisions and spending time with those you love is the only thing worthwhile.
NOTE: Our Inspire Community partner, the Bladder Cancer Advocacy Network, will have a webinar on February 3 called, “Health Related Quality of Life After Radical Cystectomy | What a large study tells us about the ‘new normal’ after bladder removal.” Register for the webinar here.
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