Treatment of Neuroendocrine Tumors of the Bladder with Muscularis Propria Invasion
For neuroendocrine tumors of the bladder involving the muscularis propria, neoadjuvant chemotherapy using small cell lung cancer regimens (such as cisplatin/etoposide) followed by radical cystectomy with bilateral pelvic lymphadenectomy is the recommended treatment approach. 1
Initial Evaluation and Staging
Before treatment, complete staging evaluation must include 1:
- Imaging of chest and cross-sectional imaging of abdomen/pelvis with IV contrast (if not contraindicated)
- Laboratory evaluation including comprehensive metabolic panel, complete blood count, liver function tests, alkaline phosphatase, and renal function
- Exam under anesthesia at time of TURBT
- Bone scan if indicated (elevated alkaline phosphatase or pain complaints) 1
An experienced genitourinary pathologist must review the pathology when neuroendocrine features are suspected, as these variant histologies require specialized treatment approaches. 1
Primary Treatment Strategy
Neoadjuvant Chemotherapy
Neoadjuvant chemotherapy using small cell carcinoma regimens is strongly recommended before definitive local treatment. 1 The NCCN guidelines specifically state that any small cell component or neuroendocrine features should be treated with:
- Primary chemotherapy regimens similar to small cell lung cancer 1
- Cisplatin is FDA-approved for advanced bladder cancer and forms the backbone of treatment 2
Definitive Local Treatment Options
Following neoadjuvant chemotherapy, two approaches are supported 1:
1. Radical Cystectomy (Preferred for most patients):
- Bilateral pelvic lymphadenectomy must be performed, including at minimum common, internal iliac, external iliac, and obturator nodes 1
- This provides the most definitive local control
2. Bladder-Sparing Approach (Selected cases):
- Maximal TURBT followed by concurrent chemoradiotherapy 1
- Requires careful patient selection and multidisciplinary discussion 1
- Recent literature shows equivalent survival for localized disease treated with chemoradiotherapy combined with bladder-sparing surgery versus radical cystectomy 3
Treatment Algorithm Decision Points
Choose radical cystectomy when:
- Patient is medically fit for major surgery 1
- Tumor is large or multifocal
- Complete TURBT cannot be achieved 1
Consider bladder preservation when:
- Patient has significant comorbidities precluding cystectomy 1, 3
- Patient strongly desires bladder preservation after informed counseling
- Complete or near-complete TURBT is achievable 1
Important Clinical Caveats
Neuroendocrine tumors of the bladder are highly aggressive: They frequently present at advanced pathologic stage and require more intensive treatment than conventional urothelial carcinoma 3. Standard chemotherapy regimens for urothelial carcinoma (such as MVAC) are not effective for neuroendocrine histology 1.
Muscularis propria invasion significantly worsens prognosis: Once bladder cancer invades beyond the muscularis propria, the likelihood of metastatic disease increases substantially, with approximately 50% of patients developing metastatic recurrence even after radical cystectomy 4. This underscores the critical importance of neoadjuvant chemotherapy.
Pathologic distinction is crucial: In TURBT specimens, distinguishing muscularis mucosae from muscularis propria can be challenging 5, 6. Bladder cancers with smooth muscle invasion of indeterminate type show significantly higher rates of muscularis propria invasion (52%) in subsequent specimens and poorer clinical outcomes 5. When muscle type cannot be determined, restaging TURBT is essential before finalizing treatment plans 5.
Post-Treatment Surveillance
Following definitive treatment 1:
- Every 3-6 months for 2 years
- Every 6-12 months for years 2-3
- Annual chest imaging to year 5
- Optional annual upper tract imaging with CT or ultrasound
The lung is the most common site of distant metastasis after lymph nodes in bladder cancer, making chest surveillance particularly important. 7