Treatments by Stages of Bladder Cancer

Executive Summary

The treatment of bladder cancer is specified as per its different stages. Non-invasive and Non-muscle-invasive bladder cancer are classified under stage 0a, 0is, 1. Patients with low-grade non-invasive cancer (Stage 0a) are treated firstly with TURBT. Patients with high-grade non-invasive (stage Ta), carcinoma in situ(Tis), or non-muscle invasive (stage T1) bladder cancer is most commonly treated with TURBT, followed by local intravesical Bacillus Calmette-Guerin. Patients with high-grade, non-muscle-invasive bladder cancer are at higher risk of recurrence. Hence, removing the whole Bladder, called a radical cystectomy, is recommended for this type of cancer. Patients may also be treated with pembrolizumab, an immune checkpoint inhibitor that targets the PD-1 protein if the patient is at high-risk, non-muscle-invasive bladder tumour. The standard treatment for muscle-invasive bladder tumour is radical cystectomy and the removal of nearby lymph nodes. Chemotherapy and radiation therapy are also combined with radical cystectomy in case of treating muscle-invasive bladder cancer. Bladder preservation is also recommended. Chemotherapy, immunotherapy and targeted therapy are recommended for treating Metastatic urothelial cancer of stage IV.

Treatment of Bladder Cancer by Stages

Non invasive and Non-muscle-invasive bladder cancer- Stage 0a, 0is, I

Patients with low-grade non-invasive cancer (Stage 0a) are treated firstly with TURBT. Low-grade non-invasive cancer seldom turns into aggressive or metastatic cancer, but patients can have a chance to develop other low-grade cancer in the course of their life. To lower the risk of recurrence, patients may receive intravesical chemotherapy after TURBT. 

• People with high-grade non-invasive (stage Ta), carcinoma in situ (Tis), or non-muscle invasive(stage T1) bladder cancer are most commonly treated with TURBT, followed by local intravesical Bacillus Calmette-Guerin. This combined treatment narrows the risk of cancer recurrence or developing muscle-invasive cancer ^​1​. Before going for BCG, patients need another TURBT to check that the cancer has not spread to muscles. 

The first round of BCG is given for six weeks, once every week. The provider performs cystoscopy or bladder biopsy to check if cancer cells are eliminated. If cancer is gone, patients receive maintenance therapy with BCG, which is given once every three months for the first six months and then once every six months for 1 to 3 years. It will then be followed by long-term surveillance.

• People with high-grade, non-muscle-invasive bladder cancer 

People with this type of bladder cancer are at higher risk of cancer recurrence, and the tumor may return at an advanced stage with a chance of developing metastatic bladder tumour. To prevent this from happening, the urologist may recommend removing the whole Bladder, called a radical cystectomy, mainly if the person is young and has a large or several tumors during diagnosis or other aggressive features.

• People with high-risk, non-muscle-invasive bladder cancer

Patients may also be treated with pembrolizumab, an immune checkpoint inhibitor that targets the PD-1 protein. The FDA approves Pembrolizumab for bladder cancer treatment that has not responded to, BCG treatment (known as “BCG-unresponsive”) and radical cystectomy cannot be done for other medical reasons, or the patient chooses not to have that surgery.

Also Read: Treatments Approaches for Cancer

Muscle invasive Bladder cancer- Stage II and III

As this cancer has invaded the muscle layer of the bladder wall, surgery is generally the first treatment. The standard treatment is radical cystectomy and the removal of nearby lymph nodes. A TURBT can be done as a diagnostic test to determine the extent of cancer ^​2​.

Patients with muscle-invasive bladder cancer may receive systemic chemotherapy first before surgery ^​3​. They may then have radical cystectomy and urinary diversion or be given combined chemotherapy and radiotherapy treatment. Neoadjuvant chemotherapy may help destroy even the microscopic cancer cells and ultimately help the person live a longer life. The combination of two chemotherapy drugs, cisplatin and gemcitabine, can be considered a standard regimen for neoadjuvant therapy in muscle-invasive diseases.

It is significant to emphasize that neoadjuvant chemotherapy should be a cisplatin-based combination. People may receive radical surgery first whose health does not allow them to receive neoadjuvant cisplatin-based chemotherapy.

Bladder preservation

An approach that uses chemotherapy and radiation therapy after optimal TURBT may provide the same effects as removing the Bladder and is called trimodal therapy or the bladder preservation approach ^​4​.

The type of chemotherapy used for patients undergoing bladder radiation therapy can comprise: 

• gemcitabine alone
• cisplatin alone 
• a combination of mitomycin-C (available as a generic drug) and fluorouracil (5-FU).

Metastatic urothelial cancer- Stage IV

If cancer in the Bladder has spread to other parts of the body, that is, metastasized, combined treatment may be used to control and manage cancer ^​5​. Clinical trials can be a good option you should consider. 

• Chemotherapy: Presently, The first-line treatment option includes chemotherapy regimens that have cisplatin or carboplatin. These regimens include MVAC (rarely), dose-dense MVAC, and gemcitabine-cisplatin. Carboplatin regimens, such as gemcitabine, can be used to treat people with metastatic urothelial cancer who can’t receive cisplatin for whatever reasons. Chemotherapy with docetaxel or paclitaxel, or pemetrexed are alternatives for later-line treatment.
• Immunotherapy: Immune checkpoint inhibitors approved by the FDA to treat people with metastatic cancer whose tumor is not shrunk or balanced by platinum-based chemotherapy. The only immunotherapy shown to help people live longer in this phase 3 clinical trial setting is pembrolizumab.
• Targeted therapy: FDA approved erdafitinib to treat people with locally advanced or metastatic urothelial carcinoma after platinum chemotherapy did not stop cancer. Erdafitinib is a targeted therapy pointing at the DNA changes in the FGFR2 or FGFR3 genes. Patients must have their tumors tested for these changes to receive the treatment. The FDA also approved enfortumab vedotin-ejfv (Padcev) to treat locally advanced or metastatic urothelial carcinoma in people who have also received a PD-1 or PD-L1 immune checkpoint inhibitor and platinum chemotherapy and for those who can’t receive cisplatin chemotherapy and have already received one or more Treatments by Stages of Bladder Cancer.

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