Management of Squamous Cell Carcinoma of the Bulbar Urethra
Definitive chemoradiotherapy with 66-70 Gy external beam radiation plus concurrent cisplatin-based chemotherapy is the primary treatment for squamous cell carcinoma of the bulbar urethra, offering organ preservation with excellent local control. 1
Primary Treatment Approach
The bulbar urethra is part of the anterior urethra, but given its proximity to the membranous urethra and similar anatomic challenges, the treatment paradigm follows that of proximal urethral tumors:
Deliver 66-70 Gy external beam radiation therapy to gross disease with margins encompassing areas of potential microscopic spread. 1
Administer concurrent cisplatin-based chemotherapy using regimens employed for bladder cancer protocols (not conventional MVAC, which is ineffective for squamous cell carcinoma). 1
Include prophylactic pelvic lymph node irradiation given the proximal location and high risk of nodal involvement. 1
Chemotherapy Regimens
The most commonly reported effective regimens include:
5-fluorouracil (1000 mg/m²/day continuous infusion for 96 hours) plus mitomycin-C (10-15 mg/m²) administered on day 1 of radiation and repeated at day 28. 2, 3, 4
5-fluorouracil plus cisplatin has also demonstrated complete responses with durable disease control. 5
Cisplatin-based regimens are preferred as they align with bladder cancer protocols and have shown superior outcomes. 1
Surgical Considerations
Surgery is not the primary treatment modality for bulbar urethral squamous cell carcinoma due to the anatomic location making complete resection with adequate margins extremely difficult, and superior outcomes with organ-preserving chemoradiotherapy. 1
Radical cystoprostatectomy with urethrectomy may be considered only if chemoradiotherapy fails or for salvage therapy. 1
Penile-preserving surgery may be performed after chemoradiotherapy to document pathologic complete response and local control, but is not required if clinical complete response is achieved. 2, 3
Evidence Supporting Chemoradiotherapy
Multiple case series demonstrate the effectiveness of this approach:
Complete pathologic responses (Stage C to Stage T0) have been documented with combination chemoradiotherapy followed by confirmatory surgery. 3
Long-term disease-free survival exceeding 8 years has been reported with this organ-preserving approach. 2, 4
Local control rates are excellent with only urethral stricture formation as the primary late complication (occurring at 1.5-4 years post-treatment). 2
Post-Treatment Surveillance
Assess tumor status 2-3 months after completion of chemoradiotherapy with CT chest/abdomen/pelvis with contrast ± bone scan. 1
Perform cystoscopic surveillance with urethral biopsy to document complete response. 1, 2
Conduct physical examination focusing on the urethra and regional lymph nodes at each follow-up visit. 1
Monitor for urethral stricture development, which may occur 1.5-4 years post-treatment and require management. 2
Emerging Therapies for Advanced Disease
For metastatic disease with positive PD-L1 expression (tumor proportion score ≥20%), chemotherapy combined with PD-1 inhibitors (such as toripalimab) may achieve complete responses. 6
Epidermal growth factor inhibitors and cisplatin may be considered for metastatic disease, though data are limited. 7
Critical Pitfalls to Avoid
Do not treat squamous cell carcinoma with conventional MVAC chemotherapy designed for urothelial carcinoma—it is ineffective. 1
Do not deliver inadequate radiation doses below 66 Gy to gross disease—this is suboptimal for definitive treatment. 1
Do not omit prophylactic nodal irradiation for bulbar urethral tumors given their proximal location and high nodal metastasis risk. 1
Do not pursue primary radical surgery when chemoradiotherapy offers equivalent or superior outcomes with organ preservation. 1, 2