“Carcinoma in situ of the urinary bladder,” often abbreviated as “CIS,” refers to a type of cancer that is confined to the surface layer of the bladder lining. In this condition, abnormal cells are present in the lining of the bladder, but they have not invaded deeper layers of tissue or spread to other parts of the body.pillar It has the potential to develop into invasive bladder cancer if left untreated. However, not all cases of CIS progress to invasive cancer.

The outlook for individuals with carcinoma in situ of the urinary bladder varies depending on factors such as the extent of the disease, response to treatment, and overall health of the patient. Early detection and prompt treatment are crucial for improving outcomes and reducing the risk of progression to invasive bladder cancer. It’s important for individuals at risk or experiencing symptoms suggestive of bladder cancer to seek medical evaluation and appropriate management.

What is CIS?

“Carcinoma in situ of the urinary bladder” (CIS) refers to a type of bladder cancer where abnormal cells are present in the inner lining of the bladder. However, these abnormal cells have not yet invaded the deeper layers of the bladder tissue or spread to other parts of the body. In other words, the cancer cells are localized to the surface of the bladder lining. It!s non-invasive flat high-grade (G3) cancer, there is no papillary growth into the bladder lümen.

It’s important to note that carcinoma in situ is typically diagnosed through cystoscopy, where a thin tube with a camera is inserted into the bladder to visualize any abnormalities, and through biopsy, where a tissue sample is taken and examined under a microscope.

Regular monitoring and follow-up are essential for individuals diagnosed with CIS to detect any recurrence or progression of the disease early and to ensure appropriate management.

Causes and risk factors for CIS

The exact cause of carcinoma in situ (CIS) of the urinary bladder is not fully understood, but several factors are believed to contribute to its development. Additionally, certain risk factors are associated with an increased likelihood of developing CIS. Here are some common causes and risk factors:

• Smoking: Cigarette smoking is the most significant risk factor for bladder cancer, including CIS. Chemicals in tobacco smoke can enter the bloodstream and be filtered by the kidneys, ultimately concentrating in the urine and exposing the lining of the bladder to carcinogens.
• Occupational Exposure to Chemicals: Occupational exposure to certain chemicals and industrial toxins, such as aromatic amines (e.g., benzidine, beta-naphthylamine) and polycyclic aromatic hydrocarbons (PAHs), has been linked to an increased risk of bladder cancer, including CIS. Workers in industries such as manufacturing, painting, printing, and dyeing may be at higher risk.
• Chemical Exposures in the Environment: Exposure to environmental pollutants and chemicals, such as those found in contaminated water, air, or soil, may also contribute to the development of CIS. For example, drinking water contaminated with arsenic has been associated with an increased risk of bladder cancer.
• Age and Gender: Bladder cancer, including CIS, is more common in older adults, with the risk increasing with age. Additionally, men are at higher risk of developing bladder cancer than women.
• Chronic Bladder Inflammation or Infection: Chronic irritation and inflammation of the bladder lining, often due to recurrent urinary tract infections or bladder stones, may increase the risk of developing CIS.
• Previous Bladder Cancer: Individuals with a history of bladder cancer, including non-invasive tumors, have an increased risk of developing CIS.
• Exposure to Radiation: Previous exposure to radiation therapy, particularly for the treatment of other pelvic cancers, may increase the risk of developing bladder cancer, including CIS.
• Genetic Factors: While rare, certain genetic conditions and inherited mutations, such as Lynch syndrome and familial bladder cancer syndromes, may predispose individuals to develop bladder cancer, including CIS.
• Personal or Family History: Individuals with a personal history of bladder cancer or a family history of the disease may have an increased risk of developing CIS.

Is CIS dangerous and important?

Yes, “carcinoma in situ of the urinary bladder” (CIS) is both dangerous and important to address promptly. Here’s why:

• Potential for Progression: While carcinoma in situ is non-invasive, meaning it has not spread beyond the inner lining of the bladder, it has the potential to progress to invasive bladder cancer if left untreated. Invasive bladder cancer can be more difficult to treat and carries a higher risk of spreading to other parts of the body.
• Risk of Recurrence: Even after treatment, carcinoma in situ can recur. Regular monitoring and follow-up are crucial to detect any recurrence early and to initiate prompt treatment if necessary.
• Impact on Quality of Life: Symptoms of bladder cancer, including carcinoma in situ, can significantly impact a person’s quality of life. These may include blood in the urine, frequent urination, painful urination, and urgency to urinate. Addressing CIS early can help alleviate these symptoms and prevent them from worsening.
• Potential for Metastasis: While CIS is confined to the bladder lining, if it progresses to invasive cancer, there is a risk of metastasis (spread) to other organs or tissues, which can significantly worsen prognosis and treatment options.
• Importance of Early Detection and Treatment: Early detection and treatment of carcinoma in situ are crucial for improving outcomes and reducing the risk of progression to invasive bladder cancer. Prompt intervention can often effectively manage CIS and prevent it from becoming more advanced.

Complications of carcinoma in situ of urinary bladder”

Carcinoma in situ (CIS) of the urinary bladder refers to a precancerous condition where abnormal cells are found in the innermost lining of the bladder. While CIS itself is not invasive, meaning it hasn’t spread beyond the inner lining, it can progress to invasive bladder cancer if left untreated. Complications associated with CIS of the urinary bladder include:

• Progression to Invasive Cancer: One of the primary concerns with CIS is its potential to progress to invasive bladder cancer. If not treated promptly, CIS can penetrate deeper layers of the bladder lining and become invasive carcinoma, which is associated with a poorer prognosis and may require more aggressive treatment.
• Recurrence: Even after treatment, CIS can recur. Regular follow-up visits with a healthcare provider are essential to monitor for recurrence and to initiate treatment promptly if necessary.
• Metastasis: Although CIS is confined to the inner lining of the bladder, if it progresses to invasive cancer, there is a risk of metastasis, where cancer cells spread to other parts of the body. Metastatic bladder cancer can be much more difficult to treat and may have a worse prognosis.
• Need for Frequent Monitoring: Patients with a history of CIS often require regular follow-up appointments, including cystoscopies and imaging tests, to monitor for any signs of recurrence or progression to invasive cancer. These appointments can be burdensome for patients and may cause anxiety.
• Impact on Quality of Life: Treatment for CIS, such as transurethral resection of the bladder tumor (TURBT) or intravesical therapy, can have side effects that affect a patient’s quality of life. These may include urinary frequency, urgency, discomfort, or pain. Additionally, the emotional impact of living with a precancerous condition and the fear of cancer recurrence can also affect quality of life.
• Need for Aggressive Treatment: In some cases, CIS may not respond to initial treatments such as intravesical therapy, requiring more aggressive interventions such as radical cystectomy (removal of the entire bladder). This major surgery can have significant implications for a patient’s lifestyle and may require additional procedures, such as urinary diversion surgery, to maintain urinary function.
• Emotional and Psychological Impact: A diagnosis of CIS can cause significant stress, anxiety, and fear for the patient and their loved ones. Coping with the uncertainty of the condition, undergoing treatments, and facing the risk of recurrence or progression to invasive cancer can take a toll on mental well-being.

Differential diagnosis of carcinoma in situ

The diagnosis of carcinoma in situ (CIS) of the urinary bladder can be challenging and requires careful consideration of various differential diagnoses. These may include:

• Non-invasive Bladder Cancer: Conditions such as papillary urothelial neoplasm of low malignant potential (PUNLMP) or low-grade papillary urothelial carcinoma can present with similar symptoms and histological features to CIS. Distinguishing between CIS and non-invasive bladder cancer is important for determining appropriate treatment strategies.
• Inflammatory Conditions: Inflammatory conditions such as chronic cystitis or interstitial cystitis can mimic the symptoms of CIS and may cause changes in the bladder lining that resemble carcinoma in situ. Biopsy and histological examination are necessary to differentiate between inflammatory changes and CIS.
• Reactive Urothelial Atypia: Reactive changes in the urothelial lining of the bladder can sometimes mimic the appearance of CIS on histological examination. Careful evaluation of biopsy specimens by a pathologist is essential to distinguish between reactive changes and true CIS.
• Infection: Urinary tract infections (UTIs) can cause inflammation and reactive changes in the bladder lining that may be mistaken for CIS. Clinical history, imaging studies, and urine culture can help differentiate between UTIs and CIS.
• Radiation Cystitis: Patients who have undergone radiation therapy for pelvic malignancies may develop radiation cystitis, characterized by inflammation and fibrosis of the bladder wall. Radiation cystitis can sometimes mimic the appearance of CIS on cystoscopy and biopsy.
• Chemical Cystitis: Exposure to certain chemicals or irritants, such as cyclophosphamide or ketamine, can cause inflammation and ulceration of the bladder lining, which may be misinterpreted as CIS. A detailed history of chemical exposure is important in making the correct diagnosis.
• Endometriosis: In rare cases, endometriosis involving the bladder can present with lesions that resemble CIS. Careful examination and correlation with clinical findings are necessary to differentiate between endometriosis and CIS.
• Bladder Stones: Large bladder stones or calculi can cause irritation and inflammation of the bladder lining, which may mimic the appearance of CIS on imaging studies or cystoscopy. Imaging studies such as ultrasound or CT scan can help identify the presence of bladder stones.
• Benign Lesions: Benign lesions such as polyps, fibroepithelial polyps, or glandular cystitis can sometimes be mistaken for CIS on imaging or biopsy. Histological examination is necessary to differentiate between benign and malignant lesions.
• Other Malignancies: Rarely, primary bladder adenocarcinoma or squamous cell carcinoma can present with features similar to CIS. A thorough evaluation, including imaging studies, cystoscopy, and biopsy, is essential for accurate diagnosis and management.

Sypmtoms of carcinoma in situ

Symptoms of carcinoma in situ (CIS) of the urinary bladder may include:

• Hematuria (Blood in Urine): One of the most common symptoms of CIS is blood in the urine, which may make the urine appear pink, red, or cola-colored. The blood may be visible to the naked eye (gross hematuria) or detected only under a microscope (microscopic hematuria).
• Urinary Changes: CIS can cause changes in urinary habits, such as increased frequency of urination, urgency (sudden and strong urge to urinate), and dysuria (pain or discomfort during urination).
• Pelvic Pain or Discomfort: Some individuals with CIS may experience pelvic pain or discomfort, although this symptom is less common and may indicate more advanced disease.

It’s important to note that not everyone with CIS experiences symptoms, especially in the early stages. Some cases of CIS are asymptomatic and are discovered incidentally during a routine medical examination or screening test.

Because the symptoms of CIS can be similar to those of other bladder conditions, such as urinary tract infections or kidney stones, it’s essential to consult a healthcare professional if you experience any concerning urinary symptoms. Early detection and treatment of CIS can improve outcomes and reduce the risk of progression to invasive bladder cancer.

Diagnosis of CIS

The diagnosis of carcinoma in situ (CIS) of the urinary bladder typically involves a combination of medical history review, physical examination, and various diagnostic tests. Here’s an overview of the diagnostic process for CIS:

• Medical History and Physical Examination: The healthcare provider will begin by taking a detailed medical history, including asking about any urinary symptoms, past medical conditions, and risk factors for bladder cancer, such as smoking or exposure to certain chemicals. A physical examination may also be performed to assess for any signs of bladder abnormalities.
• Urine Tests: Urine tests, such as urinalysis and urine cytology, are commonly used to detect the presence of abnormal cells or blood in the urine. Urine cytology involves examining a sample of urine under a microscope to look for cancer cells shed from the bladder lining.
• Cystoscopy: Cystoscopy is a procedure in which a thin, flexible tube with a camera (cystoscope) is inserted into the bladder through the urethra. This allows the healthcare provider to visualize the inside of the bladder and identify any abnormalities, such as suspicious lesions or areas of abnormal tissue.
• Biopsy: If suspicious lesions or areas are identified during cystoscopy, a biopsy may be performed to obtain tissue samples for further evaluation under a microscope. This helps to confirm the diagnosis of CIS and assess the grade and extent of the abnormal cells.
• Imaging Studies: In some cases, imaging studies such as computed tomography (CT) scans or magnetic resonance imaging (MRI) may be ordered to evaluate the extent of the disease and determine if it has spread beyond the bladder.
• Pathology Evaluation: Tissue samples obtained from biopsy are sent to a pathology laboratory for evaluation by a pathologist. The pathologist examines the samples under a microscope to confirm the presence of CIS and provide additional information about the characteristics of the abnormal cells.

Treatment of carcinoma in situ

The treatment of carcinoma in situ (CIS) of the urinary bladder typically aims to remove or destroy the abnormal cells while preserving bladder function. Treatment options may vary depending on factors such as the extent and grade of the CIS, as well as the individual’s overall health and preferences. Common treatment options for CIS include:

Transurethral Resection of Bladder Tumor (TURBT): TURBT is a surgical procedure performed using a cystoscope inserted through the urethra into the bladder. During TURBT, the surgeon removes the abnormal cells from the bladder lining. TURBT is often the initial treatment for CIS and may be combined with other therapies.

Intravesical Therapy: After TURBT, intravesical therapy may be recommended to destroy any remaining cancer cells and reduce the risk of recurrence. Intravesical therapy involves instilling medications directly into the bladder through a catheter. The two main types of intravesical therapy used for CIS are:

• Immunotherapy: Bacillus Calmette-Guérin (BCG) is a type of immunotherapy commonly used to treat CIS. BCG stimulates the body’s immune system to attack and destroy cancer cells.
  • Chemotherapy: Chemotherapy drugs such as mitomycin C or gemcitabine may be used as intravesical therapy to kill cancer cells.

Cystectomy: In some cases, particularly if CIS is high-grade, recurrent, or associated with invasive bladder cancer, surgical removal of the entire bladder (radical cystectomy) may be necessary. During cystectomy, the surgeon removes the bladder and may create a new way for urine to leave the body, such as a urinary diversion.

Follow-Up Surveillance: After treatment, regular follow-up surveillance is essential to monitor for any recurrence or progression of CIS. Follow-up may include cystoscopy, urine tests, imaging studies, and other tests as needed.

Clinical Trials: Participation in clinical trials may be an option for some individuals with CIS. Clinical trials investigate new treatments or treatment combinations to improve outcomes for bladder cancer patients.

The choice of treatment depends on several factors, including the stage and grade of the CIS, the presence of any underlying conditions, and the individual’s preferences and overall health. It’s essential for individuals diagnosed with CIS to discuss treatment options with their healthcare team and actively participate in decision-making to develop a personalized treatment plan. Early detection and prompt treatment of CIS are critical for improving outcomes and reducing the risk of progression to invasive bladder cancer.

Prognosis

The prognosis for urinary bladder CIS can vary depending on several factors, including the extent of the disease, the aggressiveness of the cancer cells, and the effectiveness of treatment. However, in general, the prognosis for CIS of the bladder is usually favorable compared to invasive bladder cancer.

With appropriate treatment, many patients with urinary bladder CIS can achieve complete remission and have a good long-term prognosis. However, regular follow-up and surveillance are usually recommended to monitor for any recurrence or progression of the disease.

It’s important for individuals with urinary bladder CIS to work closely with their healthcare team to develop a personalized treatment plan and to discuss their prognosis in detail based on their specific circumstances. Early detection and treatment can significantly improve outcomes for patients with bladder CIS.

Summary                              

Carcinoma in situ (CIS) of the urinary bladder is a type of bladder cancer where abnormal cells are present in the inner lining of the bladder but have not invaded deeper tissues or spread to other parts of the body. CIS is considered a precancerous condition because it has the potential to progress to invasive bladder cancer if left untreated. Common symptoms include blood in the urine, urinary changes, and pelvic discomfort, although some cases may be asymptomatic. Diagnosis involves various tests such as cystoscopy, urine tests, and biopsy. Treatment options may include transurethral resection of bladder tumor (TURBT), intravesical therapy (immunotherapy or chemotherapy), or in more severe cases, radical cystectomy. Early detection and treatment are crucial for improving outcomes and reducing the risk of progression to invasive cancer.

Prof. Dr. Emin ÖZBEK

Urologist

Istanbul- TURKEY