What is the treatment for small cell carcinoma (SCC) of the bladder by stage?

Treatment of Small Cell Carcinoma of the Bladder by Stage

Small cell carcinoma of the bladder requires neoadjuvant chemotherapy using small cell lung cancer regimens followed by local treatment with either radical cystectomy or radiotherapy, regardless of stage, due to its highly aggressive nature and high metastatic potential. 1

General Principles

Small cell carcinoma of the bladder is an extremely rare and aggressive variant that behaves similarly to small cell lung cancer and requires distinct management from conventional urothelial carcinoma. 1, 2, 3

• Primary chemotherapy regimens should mirror those used for small cell lung cancer, specifically platinum-based combinations (etoposide-cisplatin being most common). 1, 3, 4
• The disease has high metastatic potential and is typically diagnosed at advanced stages, making systemic therapy essential even for apparently localized disease. 2, 3
• Coexistence with other bladder carcinoma types is common and should be identified on pathology. 1, 3

Limited-Stage Disease (≤T4aN0M0)

For surgically resectable disease, the optimal approach is neoadjuvant chemotherapy (4 cycles of platinum-based regimen) followed by radical cystectomy with bilateral pelvic lymphadenectomy. 1, 3

Surgical Approach

• Radical cystectomy should include bilateral pelvic lymphadenectomy encompassing at minimum the common iliac, internal iliac, external iliac, and obturator nodes. 1
• Surgery alone is insufficient and associated with poor outcomes. 3, 5

Bladder-Sparing Alternative

• For patients seeking bladder preservation or unfit for surgery, maximal transurethral resection followed by concurrent chemoradiation is a reasonable alternative. 1, 6
• Radiotherapy doses of approximately 60 Gy with concurrent cisplatin-based chemotherapy provide reasonable local-regional control rates (78% at 3 years) with maintained bladder function. 6
• All patients achieving complete response after chemoradiation maintained functioning bladders without significant late toxicity. 6
• Cystoscopy should be performed after completing chemoradiation to evaluate local response. 6

Chemotherapy Regimens

• Cisplatin-based combinations are preferred, with etoposide-cisplatin being the most commonly used regimen extrapolated from small cell lung cancer protocols. 3, 4
• Cisplatin is indicated as single agent or in combination for advanced bladder cancer no longer amenable to local treatments. 7

Advanced/Metastatic Disease (≥T4b, N+, M+)

Patients with unresectable or metastatic disease should receive palliative platinum-based chemotherapy using neuroendocrine-type regimens. 3, 4

• Cisplatin should be used in fit patients; carboplatin may be substituted in cisplatin-ineligible patients. 3
• Extensive-stage disease is managed with combined chemotherapy as primary treatment. 4
• Palliative radiotherapy may be used for tumor-related symptom relief. 1
• Selected patients with T4b and/or N1 disease may still be candidates for cystectomy and lymph node dissection or definitive radiotherapy after chemotherapy response. 1

Critical Considerations and Pitfalls

Staging Differences

• While some sources reference the two-stage system (limited-extensive) borrowed from small cell lung cancer, the TNM staging system for bladder cancer is also applicable. 3, 4
• Limited-stage generally corresponds to disease confined to the bladder and regional lymph nodes (≤T4aN0-1M0). 3

Prophylactic Cranial Irradiation

• The role of prophylactic cranial irradiation remains unclear and is not routinely recommended, though it warrants consideration given the disease's similarity to small cell lung cancer. 5

Prognosis

• Pure small cell carcinoma has worse prognosis than mixed histology variants. 3
• The 3-year overall survival rate is approximately 24% even with aggressive multimodal therapy. 6
• Early distant metastasis is common, occurring before local therapy completion in some cases. 6

Monitoring During Treatment

• Cisplatin requires monitoring of serum creatinine, BUN, creatinine clearance, and electrolytes (magnesium, sodium, potassium, calcium) prior to each course. 7
• Cisplatin should not be given more frequently than once every 3-4 weeks due to cumulative nephrotoxicity. 7
• Audiometric testing should be performed prior to initiating therapy and before each subsequent dose due to ototoxicity risk. 7

Follow-Up After Treatment

• After radical cystectomy: urine cytology, creatinine, and electrolytes every 3-6 months for 2 years, then as clinically indicated. 1
• Imaging of chest, abdomen, and pelvis every 3-12 months for 2 years based on recurrence risk. 1
• After bladder preservation: cystoscopy and urinary cytology every 3 months during first 2 years, then every 6 months. 1