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Urethral cancer: no consensus on treatment
The clinical outcome for locally advanced female urethral cancer with radiation or surgery alone is poor.
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A 63-year-old woman with a history of diabetes and hypertension presented to the emergency department with complaints of difficulty urinating, hematuria and suprapubic pain for one week. She denied fever, nausea, vomiting or weight loss. The physical examination was remarkable only for suprapubic tenderness. A computed tomography scan of the abdomen and pelvis demonstrated bilateral hydronephrosis and hydroureter with distension of the bladder, suggesting bladder outlet obstruction. Cystoscopy revealed a soft tissue mass at the proximal urethra with no extension to the bladder. A biopsy of the mass revealed moderately differentiated squamous cell carcinoma with basaloid features (see figure). A urinary catheter was placed. A repeat CT scan of the abdomen and pelvis showed complete resolution of hydronephrosis and hydroureter, but multiple enlarged pelvic lymph nodes including common iliac, femoral and right inguinal lymph nodes were observed.
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Source: W Razaq |
How will you manage this patient?
A) Anterior pelvic exenteration.
B) Neo-adjuvant radiation to urethra and pelvic lymph nodes.
C) Chemotherapy with cisplatin/5-FU followed by surgery.
D) Concurrent chemoradiotherapy followed by surgery.
Wajeeha RazaqCASE DISCUSSION
Urethral cancer is an extremely rare cancer, with only 600 cases reported. It is the only genitourinary malignancy more common in women than in men. The most common histologic type of urethral cancer is squamous cell carcinoma (60%) followed by transitional cell (20%) and adenocarcinoma (10%). The etiology of this disease is unclear although infections, especially with human papilloma virus, and chronic irritations are cited as possible causes. Diagnosis is usually established by cystoscopy and transurethral biopsy. A CT scan of the abdomen and pelvis and sometimes MRI of the pelvis are indicated for further staging.
Because of the rarity of this disease, no consensus has been reached on treatment modalities. Surgical excision remains the primary mode of treatment for superficial and T1 tumors, although radiotherapy alone is commonly used for nonsurgical candidates.
In 1992, Grigsby et al concluded that surgery or radiation alone might be curative in patients with tumor <2 cm in diameter (J Urol. 1992;147:1516-1520). On the contrary, no patient with a lesion >4 cm has survived five years if treated only with radiation, surgery or a combination of radiation and nonexenterative surgery. The clinical outcome for locally advanced female urethral cancer with radiation or surgery alone is poor, yielding only 20% to 30% long-term progression-free and 10% to 17% five-year overall survival.
Dalbagni et al treated six patients with locally advanced urethral cancer with high-dose brachytherapy, pelvic exenteration and external beam radiation. Two patients had complete response and four patients developed local or distant recurrence at a follow-up of 21 months (Br J Urol. 1998;82:835-841).
Johnson et al reported the results of seven patients treated with the combination of radiation and surgery (J Urol. 1989;141:615-616). Five patients were followed up to one year and only one patient was alive without disease at 12 months.
The researchers of these studies concluded that a combination of radiation followed by surgery also does not appear to be markedly superior to either treatment method alone.
In contrast, several reports have shown markedly improved progression-free and overall survival when patients with locally advanced squamous cell urethral cancer were treated with chemoradiotherapy. Similar to the treatment of squamous cell cancer of the esophagus and anal canal, the patients reported in the literature were treated with radiation and chemotherapy with mitomycin C or cisplatin/5-FU. The reported progression-free survival ranged from two to eight years. Researchers from multiple retrospective studies also reported long-term disease-free survival in patients receiving combination therapy of either radiation with chemotherapy or neo-adjuvant concurrent chemoradiotherapy followed by surgery.
This patient was treated with concurrent cisplatin/5-FU and pelvic external beam radiation. She had an excellent clinical response with complete resolution of her symptoms. A repeat cystoscopy showed no evidence of urethral lesion, but the pelvic CT scan showed persistent enlargement of common iliac nodes. She was advised to a have pelvic exenteration performed, but she opted against surgery. At present, she is alive at 30 months without progression of disease.
Unfortunately, assessing the utility of this combined therapy approach is difficult because female urethral cancer is so rare. However, multimodality therapy is the preferred treatment for those patients who can tolerate the potential toxicity of the approach.
Wajeeha Razaq, MD, is a third-year HemOnc Fellow at St. Luke’s Roosevelt Hospital Center in New York.