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Combined chemoradiation as primary treatment for invasive male urethral cancer
Marissa Kent, BS, Leonard Zinman, MD, Alex Vanni, MD.
Lahey Clinic, Burlington, MA, USA.

BACKGROUND:
Male urethral cancer is an uncommon disease entity with a dismal prognosis. Historically, males underwent disfiguring surgical excision as the primary treatment modality. An initial pilot study demonstrated success utilizing an organ preserving, chemoradiation protocol based on the treatment for squamous cancer of the anal canal. In this study we sought to evaluate the long-term effectiveness of this combined chemoradation protocol as the primary treatment for invasive carcinoma of the male urethra.
METHODS:
We retrospectively reviewed the medical records of 29 male patients diagnosed with carcinoma of the urethra between 1991 and 2014. All patients were treated at the same tertiary care referral center and received a combination chemoradiation protocol consisting of 2 cycles of 5-fluorouracil (1,000mg/m²) and mitomycin-C (10mg/m²) with concurrent external beam radiation therapy (45 to 55 Gy in 25 fractions) to the genitalia, perineum, and inguinal and external iliac lymph nodes. Salvage surgical resection was performed in patients with an initial incomplete response or recurrence. Variables assessed were presenting symptoms, age at diagnosis, tumor location in urethra, histological type, grade, stage, and tumor recurrence. 5 year overall and disease-free survival was calculated. Additionally, the need for post-radiation urethral stricture repair was analyzed.
RESULTS:
29 patients with a median age of 59 years were treated (Table 1). Median follow-up was 35.5 (4-264) months. Five of the 29 patients either are still undergoing treatment or never finished the protocol. Out of those who completed the protocol, 19 (79%) showed complete response to treatment. Five patients (21%) had no response to treatment and ultimately died of their disease, despite salvage therapy. Eight of the 19 complete responders (42%) had disease recurrence. The overall 5-year survival rate was 43%. The median overall survival was 35 months. Disease-specific and disease-free 5-year survival after chemoradiation therapy was 53% and 50% respectively. All of the patients developed some degree of post-radiation urethral stricture and 8 of 15 patients (53%) who had prolonged disease-free survival underwent complex urethral reconstruction.
No. Pts(%)
Mean age (range)58(33-87)
Presenting Symptoms:
Stricture22(76)
Mass/penile lesion14(48)
Prior urethroplasty5(17)
Pain13(45)
Hematuria11(40)
LUTS12(41)
Purulent discharge5(20)
Phimosis1(3)
Clinical Stage:
T2N03(10)
T3N010(34)
T4N04(14)
TXN12(7)
TXN27(24)
Tumor urethral location:
Pendulous12(41)
Bulbomembranous17(59)
Histology:
SCC28(97)
Adenocarcinoma1(3)
Grade:
Well differentiated3(10)
Well-mod differentiated1(3)
Moderately differentiated12(41)
Poorly differentiated13(45)

CONCLUSIONS: Combined chemoradiation is an effective treatment for advanced male urethral cancer and allows organ preservation. Our study showed high rates of success utilizing this multimodality therapeutic approach with longer disease-free survival than surgery alone and higher median overall survival than a recent study which used combination chemotherapy and surgery.


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