Immunotherapy represents a fundamental shift in cancer treatment, harnessing the body’s own defense mechanisms to identify and destroy malignant cells. This approach works by activating or “unleashing” a patient’s immune system, allowing it to recognize cancer as a threat and mount a targeted response. For bladder cancer, immunotherapy is a standard treatment option used across different disease stages, from early-stage tumors confined to the bladder lining to advanced, metastatic disease. Understanding the potential adverse effects associated with these treatments is crucial because they differ significantly from the side effects of traditional chemotherapy or radiation.
The Two Main Immunotherapy Approaches
Treatment for bladder cancer relies on two distinct methods of delivering immunotherapy, each carrying a different set of side effects. The choice of method depends primarily on the stage of the cancer.
Intravesical Therapy delivers the therapeutic agent directly into the bladder through a catheter. This method is typically used for non-muscle invasive bladder cancer (NMIBC), which is cancer confined to the lining of the bladder. Bacillus Calmette-Guérin (BCG) is the most common agent used, acting as a localized immune stimulant. The live bacteria in BCG trigger a powerful inflammatory reaction within the bladder wall, which targets the cancer cells.
The second method is Systemic Therapy, involving the intravenous infusion of immune checkpoint inhibitors. These agents are reserved for patients with advanced or metastatic bladder cancer that has spread beyond the bladder wall. Checkpoint inhibitors function by blocking proteins, such as PD-1 and PD-L1, that cancer cells use to “switch off” T-cells, thereby releasing the immune system’s brakes. Because these drugs circulate throughout the body, the resulting side effects are widespread and non-localized.
Common Systemic Adverse Reactions
Systemic checkpoint inhibitor therapy can lead to generalized adverse reactions that are not specific to a single organ. These effects arise because T-cell activation is not confined to the tumor, leading to a loss of self-tolerance in healthy tissues.
A frequently reported side effect is profound fatigue, which often does not improve with rest. Many patients also experience flu-like symptoms, including low-grade fever, chills, and generalized aches.
Skin reactions are also common, manifesting as rashes, dryness, or intense itching (pruritus). These dermatologic events signal the immune system’s widespread activation. Furthermore, a generalized inflammatory response can cause pain in the muscles (myalgia) and joints (arthralgia). These systemic effects are generally managed with supportive care and, if necessary, temporary interruption of the treatment.
Unique Bladder-Specific Side Effects
Intravesical BCG therapy produces localized adverse effects unique to this treatment, as it is delivered directly into the bladder. These reactions are highly prevalent, with up to 70% of patients experiencing some form of bladder irritation.
The most common localized effect is chemical cystitis, an inflammatory condition of the bladder lining caused by the intense immune response. This inflammation leads to uncomfortable lower urinary tract symptoms, including urgency, frequency, and a burning sensation during urination (dysuria).
Temporary hematuria (blood in the urine) is another frequent occurrence, usually resolving within a few days after the treatment session. Bladder spasms and localized discomfort can also be present. While rare, there is a serious risk of systemic BCG infection (BCG sepsis) if the bacteria enter the bloodstream, particularly if the bladder lining was recently injured. This disseminated infection requires immediate intervention with anti-tubercular medication and broad-spectrum antibiotics.
Recognizing and Managing Severe Immune Reactions
While common side effects are often manageable, systemic immunotherapy carries the risk of severe, less common complications known as immune-related adverse events (irAEs). These serious irAEs typically affect the lungs, colon, liver, and hormone-producing glands.
Pneumonitis, inflammation of the lung tissue, can cause cough and shortness of breath, which may be mistaken for a respiratory infection. Colitis, inflammation of the colon, leads to symptoms like severe diarrhea, abdominal pain, and blood or mucus in the stool. Hepatitis, or liver inflammation, is often detected through routine blood tests showing elevated liver enzymes.
Endocrine system problems, known as endocrinopathies, can affect glands like the thyroid or pituitary gland, causing hormone imbalances that require lifelong replacement therapy. Because these reactions can be life-threatening, patients must contact their oncology team immediately if they experience any new or worsening symptoms.
The primary strategy for managing moderate to severe irAEs involves quickly halting the immunotherapy and initiating systemic corticosteroids. Corticosteroids work to suppress the overactive immune response that is attacking healthy tissues. The dose and duration of the corticosteroid treatment are adjusted based on the severity of the reaction and how quickly the symptoms resolve. For severe (Grade 3 or 4) irAEs, treatment is typically suspended and may be discontinued permanently.