Staging and Treatment of Bladder Cancer

Introduction to Bladder Cancer Staging

The American Joint Committee on Cancer (AJCC) recommends using the TNM (Tumor, Node, Metastasis) system, 8th edition, for staging bladder cancer, which provides the framework for all treatment decisions 1, 2
The TNM system includes T stage (depth of tumor invasion), N stage (number and location of metastatic regional lymph nodes), and M stage (presence of distant metastases) 1, 2

The National Comprehensive Cancer Network (NCCN) recommends transurethral resection of bladder tumor (TURBT) with bimanual examination under anesthesia to assess depth of invasion and obtain muscle in the specimen 5, 3
Selected mapping biopsies and prostatic urethral biopsy are recommended if sessile tumor, carcinoma in situ (CIS), or high-grade disease is suspected 5
Second-look TURBT is mandatory for high-grade T1 tumors to ensure complete resection and accurate staging 5
For muscle-invasive bladder cancer (MIBC, ≥T2), CT abdomen and pelvis with contrast is the primary staging modality, which identifies extravesical extension, lymphadenopathy, and distant metastases (lung, liver, bone) 6, 1

For non-muscle-invasive bladder cancer (Ta, T1, Tis), the NCCN recommends TURBT alone with surveillance cystoscopy for low-risk disease, and TURBT followed by intravesical BCG immunotherapy for high-risk disease 5, 8
For muscle-invasive bladder cancer (Stage II and IIIA: T2-T4a, N0-N1), neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy with pelvic lymphadenectomy is the reference standard treatment 1, 2, 4
For Stage IIIB disease (T1-T4a, N2-N3), treatment lacks strong prospective data, but downstaging chemotherapy or chemoradiotherapy can be effective 4
For Stage IV disease (M1 or T4b), enfortumab vedotin + pembrolizumab is preferred first-line treatment for patients with ECOG 0-1, and platinum-based combination chemotherapy is recommended for cisplatin-eligible patients 10, 8

Clinical staging by TURBT and examination under anesthesia frequently understages patients compared to final pathology at cystectomy, primarily due to underestimation of invasion depth and lymph node involvement 5, 3
Ensure adequate muscle sampling in TURBT specimen to distinguish T1 from T2 disease, and perform second-look TURBT for high-grade T1 tumors—residual disease found in up to 50% of cases 5
Lymph node staging limitations include size-based criteria missing microscopic metastases in normal-sized nodes, and neither 6th nor 7th edition TNM nodal staging performs well as a prognostic tool 6, 1
Cisplatin eligibility assessment is mandatory before treatment planning, and never substitute carboplatin for cisplatin in the perioperative setting—not equivalent efficacy 10