Types of Treatment for Bladder cancer

Executive Summary

The different types of standard treatments for bladder cancer are explained in detail. Common treatments are used along with the integration of effective treatment planning. Surgery, Transurethral resection of bladder tumor (TURBT), Partial cystectomy, and Radical cystectomy are the most common treatment for bladder cancer. The treatment for bladder cancer also leads to several side effects. Other treatment of bladder cancer involves chemotherapy (intravesical and systemic chemotherapy), radiation therapy, immunotherapy (local immunotherapy involving Bacillus Calmette-Guerin (BCG), Interferon involving Roferon-A, Intron A, Alferon). Systemic immunotherapy consists of the use of immune checkpoint inhibitors. Targeted therapy consists of the approval for medication, mainly for Balversa® (erdafitinib) and Padcev™ (enfortumab vedotin-ejfv). Palliative care is another treatment approach for bladder cancer to managemental, physical or financial concerns. It mainly includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies. 

Treatment of Bladder Cancer

Treatment for bladder cancer depends on the disease’s stage and the patient’s health history, age, and preferences ^​1​.

Surgery

Surgery is usually the first-line treatment for bladder cancer that has not spread to other body parts. For some patients with bladder cancer, a bladder preserving approach can be recommended, while for others, removing the bladder may be the secure option to prevent cancer from spreading. Different surgery can be performed based on the stage and grade of cancer.

• Transurethral resection of bladder tumour(TURBT)

TURBT can be used both for the diagnosis and treatment of bladder cancer. The doctor inserts a thin, flexible tube into the bladder through the urethra in this procedure. A tool on the distal end of the tube removes the tumor with the help of a wire loop or burns it with electricity, and the process is called fulguration.

Transurethral resection and fulguration might be a treatment option if the cancer was diagnosed before stage 4.

For Non-muscle-invasive bladder cancer, TURBT can probably eliminate cancer ^​2​. Yet, the doctor may recommend additional treatments to reduce the risk of cancer recurrences, such as intravesical chemotherapy or Immunotherapy. Chemotherapy is generally used in muscle-invasive bladder cancer. 

• Partial cystectomy

A low-grade tumour has spread to the bladder wall, but only in one part of the bladder; partial cystectomy can be recommended. It removes part of the bladder and nearby lymph nodes. The person who has gone through a partial cystectomy can urinate normally but may have a frequent urge to urinate. 

Also Read: Integrative cancer treatment

• Radical cystectomy

When cancer has invaded the muscle wall or has spread to a more significant portion of the bladder, doctors may recommend a complete cystectomy ^​3​. The process also removes reproductive organs like the uterus, ovaries, fallopian tube, cervix and part of the vagina in women, and for men, it includes prostate and seminal vesicles.

After the bladder is removed, a new passage for urine has to be created called urinary diversion.

• The doctor may use a section of the small intestine or colon to divert urine to a stoma or ostomy outside the body. A urinary bag is required to collect and drain urine. Hence, a patient must wear a urinary bag.
• Surgeons can use a portion of the small or large intestine to present a storage pouch inside the body. In this procedure, urinary bad is not required.
• The surgeon can connect the pouch to the urethra for some patients, creating a neobladder to pass the urine out of the body. However, the patient may require to insert a thin tube known as a catheter if the neobladder is not fully emptied of urine. Patients with neobladder will not have the urge to urinate and must learn to urinate on schedule.
• For other patients, a pouch made of the small intestine is created and connected to the skin on the abdomen or belly button through a small stoma (an example is an “Indiana Pouch”). 

Side effects of Bladder surgery

Not having a bladder can probably affect a person’s quality of life; hence finding a possibility to keep a part or complete bladder is an important treatment goal. The side effects of bladder surgery depend upon the procedure adopted, and the side effects may include:

1. Infection
2. Blood clots or bleeding
3. Prolonged healing time
4. Discomfort after surgery and injury to a nearby organ
5. Urine leak after cystectomy or urinary diversion
6. Erectile dysfunction. If a nerve-sparing cystectomy is performed, the man may be able to have a normal erection.
7. Loss of stamina or strength for some time.
8. Damage to nerves in the pelvis or sexual difficulties in men and women is fixed with further treatment.

Chemotherapy 

Some patients may receive chemotherapy post-surgery from killing left out cancerous cells, called adjuvant chemotherapy, while some may receive chemotherapy first called neoadjuvant therapy. 

Chemotherapy uses medicine to kill or stop the growth of cancerous cells. Depending upon the stage, different chemotherapy is given. The point that makes a difference is how the chemotherapy enters the body and which cells it affects.

Two types of chemotherapy can be used for bladder cancer.

• Intravesical chemotherapy

The urologist inserts a tube through the urethra and delivers medicine directly into the bladder. It is also known as regional or local chemotherapy. It influences the affected area and causes little to no damage to other cells. It’s usually used after a TURBT or to treat noninvasive bladder cancer ^​4​. Mitomycin-C (available as a generic drug), gemcitabine (Gemzar), docetaxel (Taxotere), and valrubicin (Valstar) are the drugs used most often for intravesical chemotherapy.

• Systemic chemotherapy

It is taken as pills or injected through an IV. Hence medicine reaches the cancer cells through the bloodstream. For patients whose cancer has metastasized, that is, stage 4 bladder cancer, this is considered the primary treatment. Systemic chemotherapy may also be used to help shrink a tumour before surgery, to help keep cancer from recurring, or to accompany radiation therapy. It’s commonly used if bladder cancer is muscle-invasive.

The most common administration for systemic, or whole-body, chemotherapy to treat bladder cancer include:

• Cisplatin and gemcitabine
• MVAC combines four drugs: methotrexate (Rheumatrex, Trexall), vinblastine (Velban), doxorubicin, and cisplatin
• Dose-dense (DD)-MVAC with growth factor support: This is the same regimen as MVAC, but there is less time between treatments and has replaced chiefly MVAC
• Carboplatin (available as a generic drug) and gemcitabine
• Docetaxel or paclitaxel (available as a generic drug)
• Pemetrexed (Alimta)

Side effects of chemotherapy depend on the individual drug that has been given to the patient, the combination regimen, and the dose used. The side effects can include fatigue, risk of infection, blood clots and bleeding, loss of appetite, taste changes, nausea and vomiting, hair loss, and diarrhoea. These side effects usually deteriorate after treatment is finished.

Radiation Therapy

Radiation therapy uses high-energy X-rays or particles to kill cancer cells. For patients who can’t have surgery or chemotherapy or patients who underwent surgery that didn’t remove the whole bladder, Radiation therapy is a way to treat early-stage bladder cancers. Radiation therapy is recommended to treat stage 4 bladder cancer that has metastasized or reduced or avoided symptoms and improved quality of life.

Radiation therapy and chemotherapy together may be used to treat cancer that is confined only to the bladder:

• To destroy any cancer cells present after optimal TURBT, all or part of the bladder does not have to be removed compulsorily. 
• To relieve symptoms caused by pain, bleeding, or blockage caused by the tumour.

For bladder cancer, side effects can occur in the pelvic or abdominal area, including bladder irritation, an increase in urine frequency during the treatment and bladder and rectum bleeding; other side effects may occur less commonly.

Immunotherapy

Immunotherapy, a type of biological therapy, uses artificial or natural substances to harness our immune system to fight. 

Local Immunotherapy

• Bacillus Calmette-Guerin (BCG)

This immunotherapy drug for bladder cancer is a weakened mycobacterium called BCG (similar to the bacteria causing tuberculosis). BCG, placed directly into the bladder with a catheter, attaches itself to the inner bladder lining and encourages the immune system to destroy cancer cells ^​5​. It is called intravesical therapy. 

BCG can cause fever, chills, flu-like symptoms, fatigue, burning sensation, and bleeding from the bladder.

• Interferon (Roferon-A, Intron A, Alferon)

Interferons are sometimes combined with BCG if using BCG alone does not help treat cancer.

Systemic Immunotherapy

• Immune checkpoint inhibitors

Immune checkpoint inhibitors help the body’s immune system to destroy cancer. They block cancer cells’ proteins, making it harder for the immune system to find and attack them. It is recommended if: 

• Cancer recurs after treatment.
• Cancer has spread to other parts(Stage 4).
• Advanced cancer does not get worse during chemotherapy.
• Because of health conditions, the patient cannot be treated with certain chemotherapy drugs.
• The patient has a specific type of bladder cancer that hasn’t grown into the bladder’s muscle wall but isn’t shrinking after BCG.

Targeted therapy

Targeted therapy aims at any factor contributing to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. These treatments are typical and do not harm surrounding cells like those in chemotherapy or Radiotherapy.

Not all bladder tumours have the same cellular traits, so doctors may recommend testing to understand better changes in the individual tumour’s genes and proteins.

Two targeted therapies are approved for two specific types of cancer patients:

• Balversa® (erdafitinib) – It’s used when chemotherapy hasn’t worked as a treatment. It is for people with particular locally advanced or metastatic bladder cancer and specific changes—or mutations—in the tumour. Common side effects of erdafitinib may include increased nausea, fatigue, phosphate level, mouth sores, diarrhoea, change in appetite and taste, dry mouth/skin, nails separating from the nail bed or poor nail formation. 
• Padcev™ (enfortumab vedotin-ejfv) If specific Immunotherapy or chemotherapy doesn’t work for a patient, he can go for this treatment. Padcev is a monoclonal antibody therapy that makes a protein that attacks cancer cells. It delivers a chemotherapy drug directly to the tumour. Common side effects of enfortumab vedotin-ejfv include a change in appetite and taste, fatigue, dry eye, itching, peripheral neuropathy, rash, hair loss, nausea, diarrhoea, dry skin, and elevated blood sugar, among others. 

Palliative Care

Cancer and its treatment have side effects that can be mental, physical or financial and managing the products are palliative or supportive care.

Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies. 

Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of cancer or age, any person may receive this type of care.

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