Local advanced transitional cell cancer and squamous cell cancer of the urethra treated with neoadjuvant chemotherapy followed by radical surgery E.H. Abdel Goad, T. De Bastiani and S. Ramksoon Department of Urology, Nelson R Mandela School of Medicine, Durban, South Africa Correspondence to: Dr Ehab. H. Abdel Goad,Private Bag 7, Congella 4013 Durban, South Africa (E-mail:[email protected])Phone :031 2604312 Fax : 01 2604340 Abstract Background: Primary urethral cancer is rare, accounting for less than 1% of all malignancies. The management of the urethral cancer depends on several factors which includes the clinical stage and the location of the lesion. Local surgical excision is the treatment of choice for the distal and low stage tumor while proximal tumors need more radical surgery. Aim: To report a case of a young African man who presented with locally advanced squamous cell cancer of the periurethral tissues and underlying isolated transitional cell cancer of the urethra. Case report: A 51-year-old man presented with a locally advanced squamous cell cancer of the periurethral tissues as well as an underlying isolated transitional cell cancer of the urethra. Chemotherapy with Gemcitabin and Cisplatinum together with local radiation to the pelvis and the perineum was given. There was remarkable regression of the tumour was identified by clinical examination and computed tomography scan after the treatment. The patient subsequently underwent cystoprostatectomy, radical penectomy, excision of the scrotum and ileal conduit. He recovered well postoperatively. Conclusion: Multimodal therapy combining chemotherapy and surgical resection should be used in locally advanced cases to improve the patient's survival chance. Key words: Urethral cancer, Transitional cancer, Squamous cell cancer, Chemotherapy Introduction Case report Carcinoma of the male urethra is an uncommon neoplasm, accounting for less than 1% of all malignancies1. Aetiologic factors identified include chronic inflammation owing to a history of frequent sexually transmitted diseases, urethritis, and urethral stricture, and there is likely a causal role for human papillomavirus 16 (HPV 16) in squamous cell carcinoma of the urethra2. Patients with urethral cancer present with different lower urinary tract symptoms. The most common presenting symptom is urethral bleeding and urethral mass on physical examination. Other clinical features include urinary retentions, abscess and urethrocutaneous fistula. A case of urethral cancer treated in Nelson R Mandela school of medicine, Durban, South Africa is presented. A 51-year-old male presented with acute urinary retention and a 1-year history of perineal mass and scrotal sinus. His past genitourinary history was insignificant while his past medical history included diabetes mellitus, hypertension and tobacco abuse. On physical examination, the patient had a large tender perineal mass fixed to the symphysis and the iliac bone and displacing the scrotum upward and anteriorly. The corpora spongiosum and cavernosum were involved up to the middle of the shaft of the penis (Figure 1). On digital rectal examination the mass was palpable and fixed to the pelvic structures. In addition to the mass, there was a scrotal sinus discharging seropurulent fluid. Port Harcourt Medical Journal 2007; 1: 208-211 208 Local advanced transitional cell cancer E.H. Abdel Goad, T. De Bastiani and S. Ramksoon Figure 4. The excised penis and scrotum Figure 1. Scrotal fistula and solid mass pushing the scrotum anterior and superior. Figure 2. Voiding cystourethrogram showing complete obstruction of the anterior urethra with an irregular posterior urethra and multiple filling defects. Figure 3. CT Scan showing a solid mass replacing the corpora spongiosum and cavernosum. Port Harcourt Medical Journal 2007; 1: 208-211 Figure 5. The urinary bladder with tumor extension to the membranous urethra and two stones. Voiding cystourethrogram showed complete obstruction of the anterior urethra with an irregular posterior urethra and multiple calculi (Figure 2). Further evaluation consisted of a Tru-cut biopsy of the mass which revealed features consistent with high grade squamous cell carcinoma. A computerized tomography (CT) of the chest, abdomen and pelvis revealed a large mass involving the corpora spongiosum and cavernosum with attachment to the rectum and the pelvic bone and generalized pelvic lymphadenopathy. The patient received broad spectrum antibiotics and neo-adjuvant chemotherapy in the form of three cycles of cisplatinum, mitomycin and 5209 Local advanced transitional cell cancer flurouracil. Clinical examination which was done on completion of the chemotherapy treatment revealed marked decrease in the size of the mass, although still palpable, and closure of the scrotal sinus. Repeat CT scan confirmed the clinical findings and did not detect any abdominal lymphadenopathy (Figure 3). The patient was scheduled for radical penectomy, scrotectomy, cystoprostatectomy, pelvic lymphadenectomy and urinary diversion ( ileal conduit ). The mass was excised with difficulty, as it was attached to the iliac bone and to the rectum. Accidental rectal injury was encountered during excision of the bladder and was primarily repaired using vicryl and anal dilatation. Figures 4 and 5 show the external genitalia and the excised bladder . The testes were inserted into an inguinal pouch bilaterally. The perineal wound was left open for future skin graft. The patient developed rectal fistula to the perineal wound. This closed in 10 days of low residue diet. The perineal wound was subsequently covered with skin graft. The pathological specimen showed a locally advanced high grade transitional cell carcinoma of the urethra with local extension to the corpus cavernosum. The surgical margin was free of tumour and the lymph nodes showed reactive lymphadenopathy. There was no evidence of squamous cell cancer in the specimen. In addition, a focal prostatic adenocarcinoma with Gleason score of 6 (3+3) was demonstrated within the prostate specimen. Due to the nature of the tumour, the patient was administered adjuvant chemo-radiotherapy using Gemcitabin and Cisplatinum with local radiation to the pelvis and the perineum. The patient remains disease free six months post treatment. Discussion The histologic subtype of urethral cancer varies by anatomic location. Carcinomas of the prostatic urethra are of transitional cell origin in 90% and of squamous cell origin in 10%, carcinomas of the penile urethra are of squamous cell origin in 90% and of transitional cell origin in 10%, and Port Harcourt Medical Journal 2007; 1: 208-211 E.H. Abdel Goad, T. De Bastiani and S. Ramksoon carcinomas of the bulbomembranous urethra are of squamous cell origin in 80%, of transitional cell origin in 10%, and adenocarcinoma or 3 undifferentiated in 10% . Staging of the tumour includes clinical examination, cystoscopy, and bimanual palpation to evaluate the extent of local involvement of the tumor. Transurethral or needle biopsy of the lesion, and of the prostate if indicated, is also performed as part of the staging (Table 1). Table 1. Clinical-pathologic staging for urethral cancer Primary tumor Tx T0 Ta Tis T1 T2 T3 (T) (men and women) Primary tumor cannot be assessed No evidence of primary tumor Noninvasive papillary, polypoid, or verrucous carcinoma Carcinoma in situ Tumor invades subepithelial connective tissue Tumor invades any of the following : corpus spongiosum, prostate, periurethral muscle Tumor invades any of the following: corpus cavernosum, beyond prostate capsule, anterior vagina, bladder neck Tumor invades other adjacent organs T4 Regional lymph nodes (N) Nx Regional lymph nodes cannot be assessed N0 No regional lymph nodes metastasis N1 Metastasis in a single lymph node, 2 cm or less in greatest dimension N2 Metastasis in a single lymph node, more than 2 cm in greatest dimension, or in multiple lymph nodes Distant metastasis (M) Mx M0 M1 Distant metastasis cannot be assessed No distant metastasis Distant metatasis Urethral cancer staging in accordance with the criteria outlined by the American Joint Committee on Cancer Staging System No consensus has been reached regarding the optimal therapeutic approach for urethral tumours due to the small number of patients treated at individual institutions. The overall management depends on the site and the stage of the tumor. Distal urethral tumours are usually of low stage and are amenable to local excision with good overall prognosis. On the contrary, proximal urethral tumours present with higher stage require 210 Local advanced transitional cell cancer multimodality approach for treatment with overall poor prognosis. The 5-year disease-free survival rate of proximal urethral tumours is only 20% to 30% with surgical therapy only4. R a d i c a l c y s t o p r o s t a t e c t o m y, p e l v i c lymphadenectomy, and total penectomy are usually required. Extending the operation to include incontinuity resection of the pubic rami and the adjacent urogenital diaphragm may improve the margin of resection and local control2. Most of the urethral tumuors are high stage, making surgical resection inadequate as the sole modality of treatment. Furthermore, in several series, patients who received radiation therapy and then salvage surgery seemed to fare worse than if surgery was performed first 5, 6. Disease-free survival rate of 60% to 100% was achieved, in reported cases, with the use of chemotherapy (5-Fluorouracil, Cisplatin or Mitomycin C) and radiation therapy as neoadjuvant treatment 7 - 9. Patients with low stage urethral tumours had good treatment outcomes regardless of treatment employed (surgery versus multimodal therapy) and local surgical therapy should be used as the primary treatment. Insufficient data are available to recommend certain modality of treatment in advanced urethral tumours. However, previous series have found a high incidence of local recurrence and metastasis with single modality therapy1,4-9. From the literature, it appears that multimodality therapy may provide better diseasefree survival. In addition to local control, chemotherapy treats micro metastases associated with such aggressive tumuor with possible benefit to the overall survival. In our case the patient had clinically and radiologically irresectable locally advanced urethral tumour. The tumour showed remarkable regression on chemotherapy which encouraged the decision for a radical surgical excision. The surgical margin was clear and in spite of the development of recto cutaneous fistula the patient did well. Although the radiotherapy may increase the morbidity of the treatment, the risk of the tumour recurrence should Port Harcourt Medical Journal 2007; 1: 208-211 E.H. Abdel Goad, T. De Bastiani and S. Ramksoon be considered. Adjuvant chemo-radiotherapy was chosen because the tumuor was locally advanced and of high grade. References 1 2 3 4 5 6 7 8 9 Levine RL. Urethral cancer. Cancer 1980; 45 ( 7 Suppl ): 1965-1972. Donat SM, Cozzi PJ, Herr HW. Surgery of penile and urethral carcinoma. 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