Current Treatments in Bladder Cancer

Bladder cancer is one of the most commonly occurring cancers, usually forming from the urothelial cells lining the inside of the bladder.1 Stretching from 2 inches to more than 6 inches in length, the bladder has the capacity to hold approximately 16 to 24 oz of urine (400-600 mL), with the urge to urinate often occurring when the bladder is approximately one-fourth full.² During urination, urine initially moves from the kidneys to the bladder through ureters, which are 2 tubes connecting each organ. The urine then passes through the urethra.³

Although bladder cancer usually starts from the urothelial cells inside the bladder, those cells are also found in the kidneys and ureters, meaning cancer can develop in these areas as well. Usually, bladder cancer can be detected during the initial stages; however, following treatment, bladder cancer has a high rate of recurrence. Considering this risk, routine checks are recommended for patients who experienced successful treatment outcomes.¹

Symptoms of bladder cancer can include blood in the urine, or hematuria, which makes urine bright red. Additional symptoms may include frequent urination, which may be painful, and severe, persistent back pain.¹

Each year in the United States, approximately 55,000 men and 17,000 women are given a bladder cancer diagnosis, with approximately 12,000 men and 4600 women subsequently dying from the disease.⁴ However, in 2021, the number of new diagnoses for bladder cancer reached approximately 83,000 patients. With this increase, it is estimated that approximately 2.4% of the US population will receive a bladder cancer diagnosis at some point in their lives.⁵

Although it is the sixth most common cause of cancer, bladder cancer risk increases with age and is more common among men than women.⁵ Upon diagnosis, the 5-year relative survival rate for patients is approximately 77%.⁵

There are 3 main types of bladder cancer: urothelial carcinoma, squamous cell carcinoma, and adenocarcinoma. Squamous cell carcinoma is rare, especially in the United States, and is usually caused by long-term infections. Such infections tend to occur in parts of the world where parasitic infections, such as schistosomiasis, are more frequent.¹

Additionally, adenocarcinoma is even more rare than squamous cell carcinoma. Adenocarcinoma occurs in the mucus-secreting glands of the bladder.¹

Risk factors for bladder cancer include smoking, older age, male gender, and exposure to chemicals such as arsenic, manufactured dyes, textiles, and paint, as well as certain chemicals within rubber and leather products. Bladder cancer can also be caused by prior cancer treatments such as cyclophosphamide, as well as by radiation treatments to the pelvis.¹

Patients with a family history of bladder cancer involving parents, siblings, or close relatives face increased risk as well. For squamous cell bladder cancer, chronic bladder inflammation from repeated urinary infections and inflammations (cystitis) can also increase risk.¹

Diagnostics for bladder cancer can be conducted in several ways, including cystoscopy, transurethral resection of the bladder tumor (TURBT), urine cytology, or imaging tests. In cystoscopy, a scope is placed inside the bladder for examination; however, during this process, TURBT can also be conducted within the bladder by removing a sample tissue of the organ for testing.¹ For less invasive approaches, bladder cancer diagnosis can be conducted through urine cytology—which entails the examination of a urine sample—or through imaging tests such as CT, which provides images of the structure of the bladder and potential cancer.¹

After a diagnosis of bladder cancer, specialists can order further tests, such as CT scan, MRI, positron emission tomography imaging, bone scan, and chest x-ray. Based on the results, the specialists can then assign a cancer stage to the disease, which can range from 0 to IV. The lowest stage indicates a cancer confined to the inner layers of the bladder; the highest indicates that the cancer has spread to lymph nodes or surrounding organs.¹

Bladder cancer can also be classified by grade based on the appearance of the cancerous cells under a microscope. For this classification, a low grade indicates that cells are closer in appearance to normal cells, which grow slowly. A high-grade bladder cancer appears abnormal; this type of bladder cancer grows more aggressively than the low-grade tumor and may be more likely to spread to the muscular wall of the bladder and other organs.¹

The treatment options available for bladder cancer include chemotherapy, radiation therapy, immunotherapy, targeted therapy, and surgery, with the surgery option including TURBT and cystectomy. During the operation, the surgeon creates a new bladder after cystectomy, termed neobladder reconstruction.¹

During the reconstruction process, a new bladder is made from the intestines; following this, the ileal conduit technique is used, entailing the creation of a tube from a piece of the intestine that runs from the ureters and drains urine from the kidneys to outside the body. Next, the surgeon creates a continent urinary reservoir, which is another type of small pouch that holds urine for patients.¹

Chemotherapy is another treatment option for patients with bladder cancer, with options including intravesical or systemic chemotherapy. For the intravesical option, the chemotherapy drug is placed inside the bladder; BCG is the most common intravesical immunotherapy used for treating early-stage bladder cancer.⁶

For systemic chemotherapy, the medication is given either orally or intravenously. Specifically, when given with radiation, common chemotherapy drugs used are cisplatin, cisplatin plus fluorouracil (5-FU), or mitomycin with 5-FU. When chemotherapy is used without radiation, the common drugs are gemcitabine and cisplatin; a combination of methotrexate, vinblastine, doxorubicin, and cisplatin; a combination of cisplatin, methotrexate, and vinblastine; or gemcitabine and paclitaxel.⁶

If too many adverse effects (AEs) occur with a combination treatment, single therapies can be used instead. Common AEs that may be observed from these chemotherapy drugs may include nausea and vomiting, loss of appetite, hair loss, mouth sores, diarrhea, constipation, increased risk of infections, easily bleeding or bruising, and fatigue.⁶

Additional treatment options for patients with bladder cancer are PD-1 and PD-L1 inhibitors. PD-L1, a cell protein that helps the immune system defend itself, can be targeted with atezolizumab (Tecentriq; Genentech USA) and avelumab (Bavencio; EMD Serono). Alternatively, nivolumab (Opdivo; Bristol Myers Squibb Company) and pembrolizumab (Keytruda; Merck & Co) target PD-1, which is a protein on specific immune T cells that keep the cells from attacking other cells in the body.⁶

Enfortumab vedotin (Padcev; Astellas Pharma US) is an antibody-drug conjugate containing an anti–Nectin-4 antibody attached to a chemotherapy drug. This drug is used for patients with bladder cancer who have already been treated with a platinum chemotherapy drug, such as cisplatin, and immunotherapy, such as PD-1 or PD-L1 inhibitors.⁶

An additional antibody-drug conjugate option is sacituzumab (Trodelvy; Gilead Sciences), which attaches to the Trop-2 protein on the bladder cancer cells and brings the chemotherapy directly to them. This option is usually used for advanced bladder cancer that has already been treated with a platinum chemotherapy drug and immunotherapy options. It is infused into the vein once a week for approximately 2 weeks, followed by a week off.⁶

Radiation is another option and works by destroying the cancer itself. This option is often used as either a primary treatment when surgery is not an option or when the patient wishes not to pursue surgery.⁶

Targeted drug therapies are also available for bladder cancer treatment, with those that target fibroblast growth factor receptor being the most common, such as erdafitinib (Balversa; Janssen Biotech), which can be used to treat locally advanced or metastatic bladder cancer that is growing despite chemotherapy; erdafitinib is taken orally as tablets once a day.⁶

For patients with bladder cancer, the best option may include more than 1 of these treatments. Depending on the patient status and the cancer growth, a specialist may decide to pursue medication; otherwise, the best method available may be radical cystectomy, which entails removal of the entire bladder.⁵

Regardless of the therapy options and approaches taken during cancer treatment, patients should be continuously monitored and evaluated for cancer regrowth because of the high rate of recurrence following successful bladder cancer treatment.⁷ Based on the data available, continuous follow-ups have been demonstrated to support an approximate 5-year survival in 77% of patients with bladder cancer.⁵

REFERENCES

1. Bladder cancer. Mayo Clinic. August 8, 2020. Accessed September 15, 2021. https:// www.mayoclinic.org/diseases-conditions/bladder-cancer/symptoms-causes/syc-20356104
2. Bladder. Healthline. Updated January 21, 2018. Accessed September 15, 2021. https:// www.healthline.com/human-body-maps/bladder#1
3. Urinary reconstruction & diversion. Cleveland Clinic. Updated September 14, 2020. Accessed September 15, 2021. https://my.clevelandclinic.org/health/treatments/12546-urinary-reconstruction--diversion#:~:text=The%20kidneys%20filter%20your%20 blood,the%20body%20when%20you%20urinate
4. Bladder cancer. CDC. Updated October 7, 2020. Accessed September 15, 2021. https://www.cdc.gov/cancer/bladder/index.htm
5. Cancer stat facts: bladder cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Accessed September 15, 2021. https://seer.cancer.gov/ statfacts/html/urinb.html
6. Chemotherapy for bladder cancer. American Cancer Society. Updated January 30, 2019. Accessed September 15, 2021. https://www.cancer.org/cancer/bladder-cancer/ treating/chemotherapy.html
7. Treating bladder cancer. American Cancer Society. Accessed September 15, 2021. https://www.cancer.org/cancer/bladder-cancer/treating.html