Treatment of T3 N0M0 Urothelial Carcinoma with Glandular Differentiation
For T3 N0M0 urothelial carcinoma with glandular differentiation, radical cystectomy with bilateral pelvic lymphadenectomy and neoadjuvant cisplatin-based combination chemotherapy is the recommended treatment to maximize survival outcomes.
Primary Treatment Approach
- Radical cystectomy with bilateral pelvic lymphadenectomy is the standard of care for T3 urothelial carcinoma, including those with glandular differentiation 1
- The lymphadenectomy should include at minimum the common iliac, internal iliac, external iliac, and obturator nodes 1
- Neoadjuvant cisplatin-based combination chemotherapy should be administered before cystectomy, as it has demonstrated survival benefit in T3 disease (category 1 evidence) 1
- Recommended neoadjuvant chemotherapy regimens include MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) or gemcitabine-cisplatin 1, 2
Evidence for Histological Variant Management
- Urothelial carcinoma with glandular differentiation is considered to have a potentially more aggressive natural history than pure urothelial carcinoma 1
- Despite the histological variation, these tumors should be treated similarly to pure urothelial carcinoma, with the understanding of their generally worse prognosis 1
- Research has shown that patients with urothelial carcinoma with histological variations (including glandular) can achieve significant pathologic downstaging (60% vs 32% in pure urothelial carcinoma) with neoadjuvant chemotherapy 3
- This supports the continued use of neoadjuvant chemotherapy in this specific subgroup of patients 3
Timing Considerations
- Cystectomy should ideally be performed within 3 months of diagnosis if no neoadjuvant therapy is given 1
- Delaying cystectomy beyond this timeframe can negatively impact outcomes 1, 4
- A greater than 3-month delay between transurethral resection and cystectomy has shown a trend toward upstaging 5
Surgical Considerations
- An adequate lymphadenectomy is critical for both staging and therapeutic purposes 1, 6
- Extended lymphadenectomy allows for more accurate staging and improved survival in patients with non-organ confined disease 6
- Negative surgical margins are essential, as positive margins significantly impact survival outcomes 1
- The target for 30-day mortality rate after elective radical cystectomy should be <2% 1
Alternative Treatment Options
- Segmental (partial) cystectomy is generally not recommended for T3 disease, as it is reserved for select T2 tumors with specific characteristics (solitary lesion, amenable location, adequate margins, no carcinoma in situ) 1
- Bladder preservation approaches with trimodality therapy (maximal TURBT plus concurrent chemoradiotherapy) are generally not recommended for T3 disease or histological variants like glandular differentiation 1, 2
Follow-up After Treatment
- After radical cystectomy, follow-up should include:
- Urine cytology, creatinine, and electrolytes every 3-6 months for 2 years, then as clinically indicated 1, 2
- Imaging of chest, abdomen, and pelvis every 3-12 months for 2 years based on recurrence risk 1, 2
- Urethral wash cytology every 6-12 months, particularly if Tis was found within the bladder or prostatic urethra 1
- If a continent diversion was created, monitor for vitamin B12 deficiency annually 1
Common Pitfalls and Caveats
- Inadequate lymphadenectomy may miss occult nodal disease and compromise oncologic outcomes 1, 6
- Patients with histological variants like glandular differentiation should be followed more closely due to potentially more aggressive disease course 1, 7
- While some studies suggest adjuvant chemotherapy may benefit patients with invasive disease after cystectomy 8, guidelines indicate insufficient evidence for its routine use 1, except in node-positive patients 1
- Enhanced recovery protocols should be implemented to reduce perioperative morbidity 1