How do you determine if a lesion is at the Carcinoma In Situ (TIS) stage versus stage one or stage two in Urothelial Carcinoma (UTuC)?

From the Guidelines

To determine if a lesion is at the Carcinoma In Situ (TIS) stage versus stage one or stage two in Urothelial Carcinoma (UTuC), pathological examination of tissue samples obtained through transurethral resection of the bladder tumor (TURBT) with a bimanual examination under anesthesia (EUA) is essential, as it allows for the assessment of the depth of invasion and guiding of treatment recommendations 1. The staging of UTuC is crucial for determining the appropriate treatment approach, with TIS representing cancer cells confined to the urothelium without invasion, T1 indicating invasion into the subepithelial connective tissue but not the muscularis layer, and T2 meaning invasion into the muscularis layer.

• The clinical presentation and workup of patients with UTuC typically involve office cystoscopy to determine the presence of a lesion, followed by TURBT to confirm the diagnosis and determine the extent of disease within the bladder 1.
• Additional diagnostic tests, such as urine cytology, CT scan or MRI of the abdomen and pelvis, and evaluation of the upper tracts with an intravenous pyelogram, renal ultrasound with retrograde pyelogram, CT urogram, ureteroscopy, or MRI urogram, may be performed to assess the extent of disease and guide treatment decisions 1.
• The management of UTuC is based on the pathologic findings of the biopsy specimen, with attention to histology, grade, and depth of invasion, and treatment decisions are made based on the disease extent within the three general categories: non–muscle-invasive, muscle-invasive, or metastatic 1.
• Accurate staging requires experienced pathologists who can identify the tissue layers and determine the extent of invasion microscopically, and the depth of invasion is crucial for treatment decisions, with TIS and T1 potentially being managed with kidney-sparing approaches, while T2 often requires more aggressive treatment such as radical nephroureterectomy 1.

From the Research

Determining the Stage of Urothelial Carcinoma

To determine if a lesion is at the Carcinoma In Situ (TIS) stage versus stage one or stage two in Urothelial Carcinoma (UTuC), several factors and diagnostic methods are considered.

• Imaging Techniques: Computed tomography urography remains a gold standard for imaging, while PET is superior in searching for small lesions and nodal metastases 2. Contrast-enhanced ultrasonography also shows promise.
• Urine-Based Tests: Urinary cytology, fluorescent in-situ hybridization, and other urine tests are available but are either poorly researched or not accurate enough to use solely 2.
• Endoscopic Methods: During ureterorenoscopy, photodynamic diagnosis and narrow-band imaging can facilitate proper visualization of the tumor. Endoluminal ultrasonography and confocal laser endomicroscopy can potentially improve staging and grading of UTUC 2.
• Biopsy: The 'form tackle' biopsy should be performed using a basket in papillary lesions and cold-cup biopsy of flat or sessile lesions. Cryobiopsy shows promise in UTUC diagnosis but requires in-vivo studies before clinical introduction 2.

Diagnostic Challenges

Diagnosing and staging UTUC accurately remains challenging due to the rarity of the disease and the limitations of current diagnostic tools 3, 4.

• Clinical and Morphologic Correlation: Is crucial for accurate diagnosis, especially in distinguishing Carcinoma In Situ (CIS) from other conditions 5.
• Immunostaining: Techniques such as CK 20, p53, and CD44 can help in diagnosing CIS 5.
• Molecular Markers: Several molecular markers are under evaluation or used variably in clinical pathology for diagnosing and prognosticating UTUC and CIS 5, 6.

Staging and Prognosis

Staging of UTUC is critical for determining the appropriate treatment approach.

• Computerized Tomographic Urography and Biopsy: Remain the standard of care for diagnosis and staging 4.
• Preoperative Nomograms: Are vital for selecting patients for preoperative systemic chemotherapy and facilitating clinical trial enrollment 4.
• Clinicopathological Factors: Remain the main indicators of response to treatment, recurrence, and progression in CIS and UTUC 5, 6.