Local advanced transitional cell cancer and squamous cell cancer of ... treated with neoadjuvant chemotherapy followed by radical surgery

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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.
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