Bladder cancer is a condition where abnormal cells grow in the bladder lining. Treatment often begins with surgery to remove the tumor, which can range from a partial removal of the bladder to a complete removal, known as a radical cystectomy. After this primary treatment, some cancer cells might remain. These undetectable cells, called micrometastases, can lead to the cancer returning.
To address this risk, medical professionals often recommend adjuvant therapy. Adjuvant therapy is a secondary treatment administered after surgery. Its purpose is to destroy any remaining cancer cells and reduce cancer recurring. For bladder cancer, this approach aims to improve long-term outcomes for patients, especially those with high-risk disease where the cancer has invaded the muscle layer of the bladder or spread to nearby lymph nodes.
Nivolumab’s Mechanism of Action
Nivolumab is an immunotherapy drug that uses the body’s immune system to fight cancer. It belongs to a class of medications called immune checkpoint inhibitors. The immune system has built-in “checkpoints” that regulate its activity, preventing it from attacking healthy cells.
One such checkpoint involves the PD-1 protein on T-cells and its partner proteins, PD-L1 and PD-L2, on tumor cells. When PD-1 binds to PD-L1 or PD-L2, it sends an inhibitory signal that “turns off” the T-cells, preventing them from destroying cancer cells. Nivolumab blocks the interaction between the PD-1 on T-cells and the PD-L1 and PD-L2 on cancer cells. By blocking this interaction, nivolumab effectively releases the “brakes” on the T-cells, allowing them to reactivate and mount a stronger immune response against the tumor.
Receiving Adjuvant Nivolumab Treatment
Adjuvant nivolumab treatment for bladder cancer is administered to patients who have undergone radical resection of urothelial carcinoma and are at a high risk of recurrence. Patients are considered high-risk if they have muscle-invasive bladder cancer (MIBC), particularly those with pathologic T3/T4 disease or node-positive disease. Eligibility also considers whether patients received prior neoadjuvant (before surgery) cisplatin-based chemotherapy. Patients who were unable to tolerate cisplatin-based chemotherapy due to factors like impaired kidney function, significant hearing loss, or peripheral neuropathy may also be candidates for nivolumab.
The treatment involves intravenous infusion of nivolumab, commonly given in an outpatient setting. A typical dosing schedule is 240 mg every two weeks or 480 mg every four weeks. Treatment continues for up to one year, or until the disease recurs or unacceptable side effects occur.
Managing Treatment Side Effects
Patients receiving nivolumab may experience a range of side effects, immune-related adverse events (irAEs). Common side effects include fatigue, skin reactions such as rash and itching (pruritus), and gastrointestinal issues like diarrhea. Other reported side effects include musculoskeletal pain and urinary tract infections.
More specific immune-related adverse events can affect various organ systems. For example, endocrine issues like thyroiditis (inflammation of the thyroid gland) or adrenal insufficiency can occur. Liver inflammation (hepatitis) and lung inflammation (pneumonitis) are also possible. Patients are encouraged to promptly report any new or worsening symptoms to their healthcare team, as early detection and management of these side effects can help prevent them from becoming more severe. Management strategies often involve corticosteroids to suppress the immune response and alleviate inflammation.
Treatment Outlook
Adjuvant nivolumab offers a promising outlook for patients with high-risk bladder cancer after surgery. This treatment aims to reduce the risk of cancer recurrence and extend the time patients live without their disease returning. Clinical trials, such as CheckMate 274, have demonstrated that nivolumab significantly improves disease-free survival (DFS) compared to placebo.
Specifically, in patients with muscle-invasive bladder cancer, nivolumab has been shown to improve median disease-free survival. For instance, one analysis reported a median DFS of 25.6 months with nivolumab versus 8.5 months with placebo. The benefits appear to be sustained, with higher disease-free survival rates observed at 24 and 36 months in patients receiving nivolumab. Individual responses to treatment can vary, and ongoing monitoring through follow-up appointments and imaging is important to assess treatment effectiveness and detect any potential recurrence early.