Radiation cystitis (RC) is a condition characterized by inflammation and irritation of the bladder that occurs as a result of radiation therapy, typically used to treat cancers in the pelvic region such as prostate, cervical, or bladder cancer. The radiation damages the healthy cells lining the bladder, leading to various symptoms including urinary frequency, urgency, burning sensation during urination, blood in the urine (hematuria), and pelvic pain. In severe cases, radiation cystitis can cause bladder ulcers, fibrosis, and even bladder dysfunction. Management often involves symptom relief with medications, such as pain relievers and medications to soothe the bladder lining, as well as lifestyle modifications. Severe cases may require more invasive treatments such as hyperbaric oxygen therapy or surgical intervention. Early recognition and appropriate management are crucial in mitigating the impact of RC on a patient’s quality of life.

What is radiation cystitis?

Radiation cystitis is a medical condition characterized by inflammation and irritation of the bladder due to radiation therapy. It typically occurs as a side effect of radiation treatment for cancers located near the bladder or pelvic region, such as prostate, cervical, or bladder cancer. The radiation damages the healthy cells lining the bladder, leading to various symptoms such as urinary frequency, urgency, burning sensation during urination, blood in the urine (hematuria), and pelvic pain. In severe cases, radiation cystitis can cause bladder ulcers, fibrosis, and bladder dysfunction. Management often involves symptom relief with medications, such as pain relievers and medications to soothe the bladder lining, as well as lifestyle modifications. Severe cases may require more invasive treatments such as hyperbaric oxygen therapy or surgical intervention. Early recognition and appropriate management are crucial in mitigating the impact of radiation cystitis on a patient’s quality of life.

Causes of RS

Radiation cystitis is primarily caused by the use of radiation therapy in the treatment of various cancers, particularly those located in the pelvic region or near the bladder. The radiation damages the healthy cells lining the bladder, leading to inflammation, irritation, and other symptoms associated with RC. Some specific causes and contributing factors include:

• Radiation therapy: High-energy radiation beams used in cancer treatment can inadvertently damage healthy cells in the bladder lining, leading to radiation cystitis.
• Radiation dosage: The severity of radiation cystitis can be influenced by the dose and duration of radiation treatment. Higher doses of radiation or prolonged exposure increase the risk of developing radiation cystitis.
• Location of the cancer: Cancers situated near the bladder or pelvic region require radiation therapy that may affect the bladder directly, increasing the likelihood of radiation cystitis.
• Individual susceptibility: Some patients may be more susceptible to the side effects of radiation therapy, including radiation cystitis, due to factors such as age, overall health status, and genetic predisposition.
• Concurrent therapies: Radiation therapy is often combined with other cancer treatments such as chemotherapy or surgery, which may further increase the risk of developing radiation cystitis.
• Prior bladder conditions: Pre-existing bladder conditions or abnormalities may exacerbate the effects of radiation therapy on the bladder, leading to a higher likelihood of radiation cystitis.

Overall, RC is a well-recognized complication of radiation therapy for pelvic cancers, and efforts to minimize its occurrence and manage its symptoms are essential components of cancer treatment planning and patient care.

Mechanisms of radiation induced bladder injury

Radiation cystitis leads to bladder injury through several interconnected mechanisms:

• Direct Cellular Damage: Radiation therapy exposes the bladder to ionizing radiation, which directly damages the DNA and cellular structures of the bladder lining (urothelium). This damage disrupts the normal function and integrity of bladder cells, leading to inflammation and tissue injury.
• Vascular Damage: Radiation can induce vascular injury within the bladder tissue, leading to endothelial cell damage, vascular sclerosis, and thrombosis. This compromises blood flow to the bladder, resulting in tissue hypoxia and ischemia, which further exacerbates tissue damage and inflammation.
• Inflammatory Response: The initial cellular damage triggers an inflammatory response in the bladder tissue. Inflammatory mediators, such as cytokines and chemokines, are released, recruiting immune cells to the site of injury. Chronic inflammation contributes to ongoing tissue damage and dysfunction.
• Fibrosis and Scarring: Prolonged exposure to radiation can promote the accumulation of fibrous tissue (fibrosis) in the bladder wall. Fibrosis leads to structural changes, loss of elasticity, and impaired bladder function. Additionally, scarring of the bladder tissue can occur, further compromising bladder capacity and function.
• Mucosal Barrier Dysfunction: Radiation disrupts the protective mucosal barrier of the bladder, making it more susceptible to injury and infection. This disruption increases the permeability of the bladder lining, allowing toxic substances and bacteria to penetrate the bladder wall, exacerbating inflammation and tissue damage.
• Neurological Dysfunction: Radiation can damage nerves that regulate bladder function, leading to neurogenic bladder dysfunction. This dysfunction can manifest as urinary frequency, urgency, incontinence, and other urinary symptoms commonly associated with radiation cystitis.

Overall, the mechanisms of bladder injury in RC involve a complex interplay of direct cellular damage, vascular injury, inflammation, fibrosis, mucosal barrier dysfunction, and neurological impairment. These processes contribute to the clinical manifestations of radiation cystitis and can significantly impact the patient’s quality of life.

Risk factors

Several factors increase the risk of developing radiation cystitis:

• Radiation Dose and Duration: Higher doses of radiation and longer durations of radiation therapy increase the risk of bladder damage and radiation cystitis. The cumulative effect of radiation exposure on the bladder lining can lead to more severe inflammation and symptoms.
• Location of Radiation: Cancers located in close proximity to the bladder or pelvic region require radiation therapy that may inadvertently expose the bladder to radiation. The closer the tumor is to the bladder, the higher the likelihood of RC.
• Radiation Technique: Older radiation techniques that do not precisely target the tumor while sparing healthy surrounding tissues can increase the risk of radiation cystitis. Modern techniques such as intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) help minimize radiation exposure to the bladder, reducing the risk of cystitis.
• Bladder Volume and Filling: Bladder filling techniques used during radiation therapy, which aim to displace the bladder away from the radiation field, may inadvertently increase the risk of radiation cystitis if not properly managed. Overfilling or underfilling the bladder can affect radiation dose distribution and bladder irritation.
• Individual Susceptibility: Some individuals may be more susceptible to the effects of radiation on the bladder lining due to factors such as age, pre-existing bladder conditions, genetic predisposition, or concurrent medical conditions.
• Concurrent Therapies: Radiation therapy is often combined with other cancer treatments such as chemotherapy or surgery. Certain chemotherapy agents, especially those excreted through the urinary system, can exacerbate bladder irritation and increase the risk of radiation cystitis.
• Smoking: Smoking can exacerbate radiation-induced bladder damage and increase the risk of developing radiation cystitis. Smoking impairs blood flow to the bladder and interferes with tissue repair processes, making the bladder more vulnerable to radiation-induced injury.
• Prior Bladder Conditions: Pre-existing bladder conditions, such as urinary tract infections, bladder inflammation, or bladder obstruction, can increase the susceptibility to radiation cystitis by compromising the integrity of the bladder lining and impairing its ability to repair.

Understanding these risk factors is crucial in identifying individuals who may be at higher risk of developing radiation cystitis and implementing preventive measures or personalized treatment approaches to mitigate its impact.

Complications of radiation cystitis

Radiation cystitis can lead to various complications, ranging from mild to severe, depending on the extent of bladder damage and the effectiveness of treatment. Some common complications include:

• Chronic Bladder Dysfunction: Long-term inflammation and damage to the bladder lining can result in chronic bladder dysfunction, characterized by urinary symptoms such as frequency, urgency, nocturia (frequent urination at night), and urinary incontinence.
• Hematuria: One of the hallmark symptoms of RC is hematuria, or blood in the urine. While mild hematuria may resolve on its own, severe or recurrent bleeding can lead to anemia and require medical intervention.
• Bladder Ulcers: In severe cases, radiation-induced damage to the bladder lining can lead to the formation of ulcers or sores on the bladder wall. These ulcers can cause pain, discomfort, and further bleeding.
• Fibrosis and Scarring: Prolonged inflammation and tissue damage can lead to the formation of scar tissue (fibrosis) in the bladder wall. Fibrosis reduces the bladder’s elasticity and capacity, leading to urinary symptoms and potential urinary retention.
• Bladder Contracture: Fibrosis and scarring of the bladder can result in bladder contracture, a condition characterized by a decrease in bladder volume and compliance. This can lead to urinary hesitancy, incomplete bladder emptying, and urinary retention.
• Bladder Dysfunction: Severe radiation cystitis can impair bladder function, leading to difficulty in urination, urinary retention, or urinary incontinence. Bladder dysfunction can significantly impact a person’s quality of life and may require long-term management.
• Secondary Infections: Damage to the bladder lining can increase the risk of urinary tract infections (UTIs) and bladder infections. UTIs can exacerbate symptoms of radiation cystitis and may require antibiotic treatment.
• Risk of Bladder Cancer: Although rare, chronic inflammation and damage to the bladder from radiation therapy may increase the long-term risk of developing bladder cancer. Regular monitoring and follow-up with healthcare providers are essential for early detection and management.

Overall, the complications of radiation cystitis can have a significant impact on a person’s urinary function, comfort, and quality of life. Prompt recognition and appropriate management of symptoms and complications are crucial in mitigating the long-term effects of radiation-induced bladder damage.

Prevention against to RC

Prevention strategies for radiation cystitis primarily aim to minimize the risk of bladder injury during radiation therapy. While it may not be possible to entirely eliminate the risk, several measures can help reduce the severity and incidence of RC:

• Optimization of Radiation Technique: Modern radiation therapy techniques, such as intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT), allow for more precise targeting of cancerous tissues while sparing adjacent healthy organs, including the bladder. This reduces the amount of radiation exposure to the bladder, lowering the risk of radiation-induced bladder injury.
• Fractionation and Dose Limitation: Fractionation refers to dividing the total radiation dose into smaller, more manageable doses administered over several sessions. This approach helps minimize damage to healthy tissues, including the bladder, by allowing normal cells to repair between radiation sessions. Additionally, adhering to dose limitations for critical structures like the bladder can help reduce the risk of radiation cystitis.
• Bladder Filling Techniques: Some radiation therapy protocols involve bladder filling techniques, such as asking patients to drink a specified amount of water before treatment. A full bladder can help displace the bladder away from the radiation field, reducing radiation exposure to the bladder wall and minimizing the risk of injury.
• Radioprotective Agents: Certain medications or substances, such as amifostine or sodium pentosan polysulfate, have been investigated for their potential to protect normal tissues from the harmful effects of radiation. While their efficacy in preventing radiation cystitis is still under investigation, they may be considered in select cases under the guidance of a healthcare provider.
• Hydration and Urinary Management: Adequate hydration before, during, and after radiation therapy can help flush out potentially harmful substances from the bladder and reduce the concentration of urinary toxins. Additionally, maintaining good urinary hygiene and avoiding urinary catheterization whenever possible can help reduce the risk of urinary tract infections and bladder irritation.
• Patient Education and Counseling: Providing patients with information about the potential side effects of radiation therapy, including radiation cystitis, can empower them to take proactive measures to minimize their risk. Patients should be encouraged to report any urinary symptoms promptly so that appropriate management strategies can be implemented.

While these preventive measures can help mitigate the risk of radiation cystitis, it’s essential to recognize that some degree of bladder irritation may still occur in some patients undergoing radiation therapy. Close monitoring by healthcare providers and timely intervention for symptomatic relief are essential components of comprehensive cancer care.

Treatment of radiation cystitis

The treatment of radiation cystitis aims to alleviate symptoms, promote healing of the bladder lining, and prevent complications. The choice of treatment depends on the severity of symptoms and may involve a combination of the following approaches:

Medications:

• Pain relievers: Nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids may be prescribed to manage pain associated with radiation cystitis.
  • Bladder analgesics: Medications such as phenazopyridine can help relieve urinary discomfort and burning sensation.
  • Antispasmodics: Drugs like oxybutynin or tolterodine may be used to reduce urinary frequency and urgency.
  • Pentosan polysulfate sodium (PPS): PPS is a medication that helps repair the damaged bladder lining and may be prescribed for severe cases of radiation cystitis.

Bladder Irrigations: Instillation of medications directly into the bladder via a catheter may be used to deliver soothing agents or medications that promote bladder healing. Examples include sodium bicarbonate solutions or heparin.

Hydration: Maintaining adequate hydration is crucial to dilute urine and reduce its acidity, which can help alleviate symptoms and promote healing of the bladder lining.

Bladder Distension: Bladder distension involves filling the bladder with fluid to stretch its walls, which may help alleviate symptoms of radiation cystitis. However, this procedure is typically reserved for refractory cases and is performed under medical supervision.

Hyperbaric Oxygen Therapy (HBOT): HBOT involves breathing 100% oxygen in a pressurized chamber, which can help improve tissue oxygenation and promote healing of radiation-induced tissue damage. It is usually considered for severe cases of radiation cystitis resistant to other treatments.

Surgical Interventions: In rare cases of severe radiation cystitis that do not respond to conservative measures, surgical interventions such as cystectomy (removal of the bladder) may be considered as a last resort.

Symptomatic Management: In addition to specific treatments for radiation cystitis, symptomatic management strategies such as urinary catheterization, pelvic floor exercises, and dietary modifications (e.g., avoiding bladder irritants like caffeine and spicy foods) may be recommended to improve quality of life.

It’s essential for individuals experiencing symptoms of radiation cystitis to consult with a healthcare provider for proper evaluation and management. Treatment plans should be tailored to the individual’s symptoms, overall health status, and treatment goals. Close monitoring and follow-up are important to assess treatment response and adjust interventions as needed.

Summary

Radiation cystitis is a condition characterized by inflammation and irritation of the bladder resulting from radiation therapy, commonly used in the treatment of pelvic organ cancers. The radiation damages the bladder lining, leading to symptoms such as urinary frequency, urgency, burning sensation during urination, blood in the urine, and pelvic pain. Severe cases may involve bladder ulcers, fibrosis, and dysfunction. Management focuses on symptom relief with medications, bladder irrigations, hydration, and, in severe cases, hyperbaric oxygen therapy or surgical intervention. Prevention strategies include optimizing radiation technique, bladder filling techniques, and radioprotective agents. Close monitoring and prompt intervention are crucial for effective management and improvement of quality of life.

Prof. Dr. Emin ÖZBEK

Urologist

Istanbul- TURKEY