Cancer - November 1973 - Grabstald - Tumors of the urethra in men and women

TUMORS OF T H E URETHRA I N MEN
AND WOMEN
HARRY
GRABSTALD,MD*
A study of urethral tumors in men and women has been made. The 3 most
important tumors involving the male urethra are: 1. those arising in the
meatus and parameatal area; 2. quamous cell cancer of the membranous
urethra; and 3. transitional cell cancer of the prostatic urethra. T h e latter 2
respond poorly to any and all forms of therapy regardless of extent of ablative
surgical attempt or radiation therapy dosage. T h e latter prostatic urethral tumor
is also hormone-resistant. T h e most common tumors of the female urethra are
epidermoid carcinoma and adenocarcinoma. Tumors of the distal urethra
may be successfully treated by partial urethrectomy or by irradiation. For
proximal or entire urethral tumors, the prognosis with radiation or surgery
alone is poor; combined radiation and surgery is preferable.
G ROSSLY A N D MICROSCOPICALLY, THE URE-

thra in the male is divided into 3 fairly
distinct, though overlapping, areas. There is
Prostatic transitional epithelium gives rise
to transitional (urothelial) carcinoma. As will
be discussed, these are not in any fashion simi-
n o such division in the shorter and simpler lar to the much more common classical pros-
female urethra. T h e purpose of this paper is tatic adenocarcinoma, characteristically hor-
t o review our experience with the major ure- mone sensitive in the majority of cases. T h e
thral tumors in men and women and to out- squamous cell cancers arise from the membra-
line reasonable therapeutic programs for each, nous and deeper portions of the penile ure-
based not only on our experience but on thra and from the bulbar area. T h e meatus
that collected from the literature. and parameatal area give rise to two specific
tumor types, condyloma acuminatum and pap-
THEMALEURETHRA illoma.
T h e major urethral divisions, the histology PROSTATIC TUMORS

URETHRAL
of these areas, and the major tumors arising
therefrom, are depicted in Fig. 1. Transitional prostatic urethral tumors are
Prostatic glandular tumors, per se, are not most often seen in association with histologi-
pertinent to this review. Only those arising cally similar bladder tumors. Solitary papillo-
from the urethra transversing the glandular mas of the prostatic urethra without asso-
substance are included. Textbooks divide ciated co-existing or pre-existing urothelial tu-
male urethra into anterior and posterior, the mors elsewhere, such as bladder ureter or
latter including the prostatic portion. I have renal pelvis, are rare. Tumors in the prostatic
elected to define prostatic urethra as a sepa- urethra may be noted following transurethral
rate entity because of the great difference in resection of bladder tumors with implanta-
tumor types, etiology, and behavior. T h e only tion. This relates to the fact that the inci-
feature which prostatic and posterior urethral dence of posterior urethral tumors appears to
tumors have in common is a poor prognosis. be greater on followup examination than at
the time of initial bladder e v a l ~ a t i o n . ~ ~
Presented at the American Cancer Society’s National Pathology: Characteristic histopathologic
Conference on Urologic Cancer, Washington, D.C., features of the transitional prostatic urethral
March 29-31, 1973. tumor are noted in Fig. 2. I n situ carcinoma
From the Urology Service, Department of Surgery,
Memorial Sloan-Kettering Cancer Center, New York, is seen arising from mucosa of the prostatic
New York. urethra. Even though the basement membrane
Attending Surgeon, Urology Service, Memorial Hos-
pital. is intact, there are separate areas of invasive
Received for publication July 18, 1973. carcinoma infiltrating prostatic stroma.
1236
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No. 5 OF THE URETHRA
TUMORS - Grabstald 1237
MALE URETHRA
Site Tumor
\
Epide r moid
Adenoca
Posterior
Bulbous
FIG. 1. Gross anatomy of male

urethra showing sites of tumor
origin, histology of specific areas,
and major tumors arising from
these areas.
Pseudostratified
columnar
Penile Squamous
Anterior
Condyloma
Papilloma
Meatus Caruncle?
Carcinoma in situ arising in prostatic ducts cers, 7 arose in prostatic urethra. Of these, 4
is conceivably the precursor to more invasive had hematuria, 1 had prostatic calculi and 1
prostatic cancer, just as in situ cancer of blad- recurrent prostatic abscesses.46
der origin preceeds invasive cancer (Fig. 2). In one series of six patients with primary
Johnson felt that the lesions began as carci- transitional cell prostatic cancers, the ages
noma in situ in ductal epithelium with subse- ranged between 64-78 and the prostate was
quent breakthrough into prostate.36 Melicow described as hard and nodular in all. Serum
described intra-urothelial cancers as Bowen’s acid phosphatase level was normal.36 Of 14 pa-
Disease of the urinary epithelium.61Ortega re- tients with transitional cell prostatic cancer as-
ported what he described as Paget’s Disease of sociated with bladder lesions, there had been
the urethra.68 Perhaps both such lesions are recurrences in 12 of the 14. In 1, the patient
precursors of deeply infiltrating cancers. Ende, had had 54 recurrences.a6
in reviewing 200 cases of prostatic cancer In my experience, these patients with infil-
noted that 3 had transitional cell trating transitional carcinomas arising in pros-
morphology.17 He felt that the tumor very tate have had palpably hard areas.
likely began in peri-urethral and prostatic There have been no laboratory studies
ducts in the area of junction of columnar and which have been consistently useful. As indi-
transitional epithelium. cated, serum acid phosphatase is normal. Lym-
Clinical manijestat ions: Several features phangiograms may be useful. One such study
characterize these tumors. Complete resistance was obtained and revealed irregular filling
to endocrine therapy is one such feature. Poor suggestive of cancer metastasis (Fig. 3). These
response to radiation therapy and to surgery, later became “normal” following radiation
regardless of ablative attempts, is also charac- therapy. Prostatic biopsy three months follow-
teristic. There are no characteristic symptoms ing radiation therapy revealed no tumor; 4
of this lesion. In one series, most had symp months later widespread metastases appeared.
toms of prostatism.36 Of 37 male urethral can- Treatment: Transitional cell cancers of the
1238 CANCERNovember 1973 Vol. 32
FIG.2. In situ and invasive carcinoma arising as primary tumor in prostatic urethra ( ~ 8 0 ) .
prostatic urethra are successfully managed by tectomy and prostatectomy with pelvic lymph
transurethral resection in better than 50% of node dissection along with excision of endo-
cases, if the tumor is superficially infiltrating. pelvic fascia and a part of the levator muscles.
As with similar bladder cancers, recurrence oc- T h e frequency of lymph node involvement is
curs in half of the patients. not known. It is very likely that if deep pelvic
Shenasky et al. also felt that superficial low nodes are involved, prognosis is extremely
grade lesions could be adequately treated by poor as with bladder cancer involving pelvic
transurethral resection.71 I n their study they nodes. T h e value of superficial nodes dissec-
reported 4 patients and emphasized that hor- tion is not documented although my personal
monal therapy was of n o value. One patient feeling would be to recommend groin dissec-
in this series did well after transurethral resection only when nodes are palpable.
tion and cobalt therapy. Another did well fol- Mandler and Pool concluded that prostatic
lowing radical retrclpubic prostatectomy. In- urethral tumors were extensions of neoplasm
terestingly, in this patient, tumor had spread more proximally in the urinary tract, that
to seminal vesicles although lymph nodes were they responded about the same as transitional
normal. cell tumors of the bladder, and that prognosis
In the majority of instances, primary pros- varied with degree of differentiation and
tatic epidermoid tumors involve the bulk of infiltration.45 T h e good results with transur-
tine prostate so that radical prostatectomy is ethral resection in this series related to the
inappropriate and would not likely remove all fact that these tumors very likely did not orig-
tumor. Even if this were theoretically possible, inate in the true prostate or in the capsule
one would be anastomosing bladder neck to area and were therefore accessible to good
the membranous urethra so that there would resection, Radiation offered no predictable re-
be n o tumor-free margin. sults and extensive transurethral resection re-
Ablative surgery should include radical cys- sulted in survivals of from 1-9 years.45 King
No. 5 TUMORS
OF THE URETHRA Grabstald 1239
FIG.3. Lymphangiogram in patient with primaly prostatic transitional cell epidermoid car-
cinoma. Very suspicious nodes are shown in the pelvis.
reported 2 patients with this tumor.39 One tatic transitional cancers without associated
was treated by transurethral resection and or- bladder tumors. All have done poorly regard-
chiectomy and died with lung metastases. An- less of therapy except 1, who remains tumor-
other had implantation of radon seeds and free 17 months after external radiation ther-
radical perineal prostatectomy, “preserving apy.
the external sphincter.” Local recurrence “re- One could justify further trials with aggres-
sponded” to external radiation. sive external radiation therapy, reserving radi-
Johnson treated 4 of 6 prostatic transitional cal surgery for radiation failures. Biopsies
cell cancers with radiation therapy alone de- should not be taken for at least 4 months fol-
livering from 4000 to 7000 r. One had radia- lowing completion of radiation.
tion plus orchiectomy and estrogens. Another While our experience is not so extensive
had estrogens, radiation, diversion, and gold that firm recommendations regarding therapy
seed implants. The treatment seemed to mo- are possible, our experience with other similar
dify the course very little in each instance, al- tumors would lead us to recommend preopera-
though relatively long survivals were noted in tive radiation therapy with planned ablative
that 2 of his 6 patients were living at 35 and surgery to include anterior exenteration.
36 months. Thus, when invasion occurs, defi- Until more information is available relative to
nitive treatment using radiation therapy, sur- the futility of deep pelvic node dissection,
gery, or a combination, is recommended. Peri- such node removal is probably indicated at
odic evaluation of the anterior urethra is the time of the anterior exenteration. Superfi-
urged.36 cial groin dissection should be carried out
We have a small series of patients with pros- when nodes are palpable.
1240 November 1973
CANCER Vol. 32
PENILE TUMORS
URETHRAL ther of glans or the penile urethra may extend
to superficial as well as to deep inguinal
T h e term “penile drethral” will be used to nodes. Drainage of the bulbous urethra is by
designate the entire spectrum of tumors which means of two lymphatic channels, one to ex-
involve other than the prostatic or meatal or ternal iliac nodes along the course of the dor-
parameatal parts. This would include the ma- sal vein of the penis beneath the infrapubic
jority of urethral tumors, the most common ligament; the second is to hypogastric nodes
arising in the bulbo-membranous region. traveling along the pudendal artery.30
Zncidence: T h e first urethral cancer was Distant metastases are relatively rare. Ka-
reported by Thiaudierre in 1834.78 Since then, plan reported distant metastases in only 29 of
about 300 cases of mPle urethral cancer have 212 patients.37 Of these, 18 had invasion of
been recorded.85 As will be emphasized, it is corpora cavernosa at the time of initial ther-
interesting that if meatal condylomas are apy.
excluded, the incidence of cancer of the Association of urethral and bladder cancer:
urethra is higher in women than in men. A special problem concerns patients with
This is especially so since most urinary tract bladder cancer. This relates to the incidence
tumors are more common in men, and be- of urethral coexistence or recurrence of dis-
cause of the greater length and complexity ease. Cordonnier reported 7 of 174 patients
of the male urethra. Among urethral tumors, treated by cystectomy to have had urethral
the epidermoid cancer of the bulbo-mem- recurrence.10 This led Cordonnier and his
branous urethra is the most common and group to suggest that urethrectomy might well
these make u p about 75y0 of the cases. Tran- be included as a routine procedure at the time
sitional cell and adenocarcinomas are less of cystectomy. T h e incidence of urethral in-
commonly seen. T h e least common urethral volvement in bladder cancer patients in our
cancer is that which arises in the prostatic series is about the same as that reported by
urethra. Cordonnier. Our procedure, in general, has
Histopathology: I n Dixon and Moore’s re- been to perform urethrectomy routinely only
view, 88% were epidermoid and 12% were when there was evidence of multiple uroth-
other histologic types.15 Zaslow and Priestly elial tumors, especially with prostatic involve-
indicated that most epidermoid tumors were ment. A cystectomy-urethrectomy specimen is
low-grade cancers.*O This has also been our seen in Fig. 4. T h e multiplicity and multicen-
experience. tricity of urothelial tumors is widely recog-
Modes of spread: Urethral cancers tend to nized.
spread by means of direct extension to adja- Etiology: T h e predisposition of long
cent structures. Involvement of the vascular standing urethral infection to tumor forma-
spaces of the corpora and of periurethral tis- tion is well known. T h e most frequent site of
sues is common. Tumors of the bulbo-mem- urethral stricture is also the most frequent site
branous urethra often invade the deep struc- of cancer. I n many patients a history of pre-
tures of the perineum including penile and existing gonorrhea is obtained. In Kaplan’s se-
scrota1 skin, urogenital diaphragm, and even ries, 37% had venereal disease, 35y0 had stric-
prostate. Posterior urethral tumors generally ture, and 7% trauma.37 Seventy-six percent of
metastasize to hypogastric and common iliac patients with an adequate history and with ur-
nodes. It is possibly as a result of penile skin ethral cancer had a preceding history of ureth-
invasion that inguinal lymph nodes are also ral stricture.15 Because normal epithelium is
involved. While there is overlapping depend- chiefly columnar, foci of squamous metaplasia
ing upon location and invasion of contiguous appear to be a likely point of origin for the
structures, in general anterior tun-lors involve predominantly epidermoid cancers.
inguinal nodes, and posterior tumors involve Diagnosis: T h e most common symptoms in-
pelvic as well as inguinal nodes. clude dysuria, discharge, decreased stream,
T h e lymphatic drainage of the male urethra pain, mass, and hematuria. A long standing
was studied by Hand.30 T h e glans drainage is history of urethral infection, stricture, and
via a plexus that anastomoses at the symphysis treatment with sounds is often obtained. I n
and empties directly into deep inguinal and earlier days, introduction of Silver Nitrate
external iliac nodes. T h e penile urethra is and other caustics into the urethra may well
drained by lymphatics accompanying those of have played a role in the pathogenesis of
the glans. It is for this reason that lesions ei- strictures and, indirectly, of tumors.
No. 5 TUMORS
OF THE URETHRA - Grabstald 1241
FIG.4. Specimen of
bladder, prostate and
urethra. Even though
multifocal bladder tu-
mors were noted, the
urethra contained no
tumor.
The duration of symptoms varies greatly. tients): and 2. Bulbo-membranous or Prostatic

Kaplan reported symptoms between 1 day and (12 patients). Prognosis is fairly good with
15 years prior to diagnosis with an average of Group 1 patients as 5 of 7 were rendered tu-
5 months.37 The most common symptoms are mor-free by either partial or total amputa-
obstruction 470/,, mass 39Yob,periurethral ab- tion. Only 2 of 12 group 2 patients, however,
scess Sl%, fistula 20%, and urethral discharge survived, regardless of extent of ablative sur-
22y0. The most frequent site of obstruction is gery. Both survivors had low-stage tumors.
in the bulbo-membranous urethra. Laboratory aides: Urethrograms are occa-
One characteristic of this tumor relates to sionally of help in defining location and ex-
the generally long time period between initial tent of tumor and may indicate spread into
symptom and confirmation of diagnosis. This the interstices if there is fistulazation. Figure
has been our experience and Mandler and 7 is a urethrogram of a patient with localized
Even though the diagnosis may be urethral tumor which occurred some 5 years
suspected for many years, biopsies often reveal after cystectomy. More extensive changes are
only chronic inflammatory disease until demonstrated in Fig. 8A. This particular pa-
deeper tissues are obtained. tient was operated upon by me 22 years ago
By the time cancers of the bulbo-membra- when he was first admitted with a diagnosis of
nous portions of the urethra infiltrate the cor- periurethral abscess with fistula formation.
pora, tumors are at least 3 cm in size. Skin ul- Biopsies revealed squamous cell cancer of the
ceration is very often among the first physical urethra within the depths of the urethroperi-
findings. The tumor may so ulcerate and in- neal fistula. Segmental resection of urethra in
volve adjacent structures that stricture can no continuity with the fistula was carried out,
longer be identified. With infection and ne- and primary end to end anastomosis was ac-
crosis a semi fluctulant mass may be noted to complished. One month following surgery
invade perineum and scrotum. With fistulae there was apparent persistence of the fistula
formation, a “water-pot perineum” results (Fig. 8B). Re-insertion of the catheter resulted
(Figs. 5 and 6). Differentiation between cancer
and periurethral abscess is often difficult. in healing of the fistula (Fig. 8C). Several
Deep biopsies must often be obtained before weeks later a urethrogram revealed good
one can make a clear cut diagnosis of tumor. healing with no fistula formation and a nor-
Nineteen cases of primary male urethral mal urethral calibre. (Fig. 8D).
cancer have been seen here and recently re- Hypercalcemia has been noted in 2 of our
viewed by Ray, Canto, and Whitmore (per- patients with urethral cancer, both extensive.
sonal communication). These were divided A parathyroid hormone-like substance is ap-
into 2 groups: 1. Pendulous urethra (7 pa- parently produced by the tumor as removal
with resulting involve-
cal advanced posterior
ment of skin of peri-

FIGS.5 and 6. Typi-
urethral carcinoma
neum and scrotum.

resulted in reduction of serum calcium to
normal levels in both patients.
Cytology: T h e cytology of urethral swab-
bings in patients with bladder cancer was
studied by Williams.86 Of 13 cystectomy pa-
tients who had urethral swabbing, 3 showed
malignant cells.
Treatment and results: There are no spon-
taneous cures reported. The median survival
of untreated patients was 3 months with a
range of 1 week to 15 months.37 Thirty pa-
tients survived more than 5 years (16%). Eigh-
ty-eight patients (4773 died in less than 5
years.
Of 15 patients in one series, most were seen
in advanced disease stages and results of treat-
ment were poor. There was one 5-year survi-
vor and he was treated by radical penectomy
and bilateral groin dissection.= Of these 15
patients, 13 had surgery and 7 had irradiation
as some part of the treatment schedule.
The extent of tumor is such that very rarely
is conservative surgery possible as in the case
alluded to in Fig. 8. Even though results are
poor, en bloc excision of perineum and all of FIG.7. Urethrogram showing multiple filling defects.
This patient had cystectomy 5 years previously. Ureth-
the external genitalia along with bilateral su- ral bleeding was noted. Urethrectomy revealed the
perficial and deep groin dissection, possibIy presence of multiple epidermoid carcinomas.
staged, appear to be the treatments of choice,
except for pendulous anterior urethral tu-
mors, where lesser surgery is possible. Poor Melanoma: About 20 primary male urethral
survival rates reflect not only advanced disease melanomas have been reported.85 The ureth-
stage but also the limitations of surgery possi- ral meatus and fossa navicularis are the most
ble under these circumstances. For example, common sites of origin. Prognosis has been
one margin of excision is limited by ischial very poor because both lymphatic and vascu-
tuberosity and inferior pubic rami. lar dissemination occur frequently and r a p
In one series, all patients except 1 died of idly. In our review of melanoma, there were 4
disease regardless of surgery or radiation involving female urethra and 2 the penis, but
therapy.46This particular patient was treated there were none involving the male urethra.12
by total penectomy and suprapubic cystotomy If the urethral melanoma is a primary and
with external radiation to the pelvis and not secondary to tumor elsewhere, ablative
para-aortic regions. Seventeen months follow- surgery is indicated. Chemotherapy and radia-
ing surgery there was no evidence of disease. tion therapy resistance is characteristic.
I n another series one 5-year survival followed
total penectomy, 3 followed excision of local URETHRAL
MEATAL TUMORS
AND PARAMEATAL
lesion with re-anastomosis of urethra, and 6
survived over 5 years after radical excision of The most important and common tumors
urethra along with prostatovesiculectomy. arising at the urethral meatal area are papillo-
Thirty-two of 36 patients in this series treated mas and condyloma acuminata. These are be-
with x rays or radium without surgery were nign tumors virtually limited to men in the
known to have died.37 20-40-year age group and are to be distin-
Of 5 patients with squamous cell cancers in guished from the “distal” urethral cancer, al-
the bulbous urethra reported by King, only 1 luded to by Mandler and P O O P and from
did well, and he was treated by cystectomy- “Tumors of Anterior Urethra Which Metas-
prostatectomy-penectomy and scrota1 resec- tasize to Inguinal Nodes.”ls
t i ~ Marshall
n ~ ~ reported 1 patient in whom Incidence: In 1891, Goldenberg reported
radical excision resulted in 5-year survival.47 condyloma acuminata (polyps) involving ure-
More extensive major ablative surgery may thra in a 24-year-old man.23 Of 200 cases of
include radical resection of pubic bone. condyloma acuminata seen in soldiers, 10 pre-
Shuttleworth reported 1- and 7-year sur- sented urethral lesions.11 We have seen 18 pa-
vivals following such a procedure in patients tients ages 21-40 with such tum0rs.3~
with posterior urethral tumors.73 Pathology: While solitary papillomas occur
Vol. 32
FIG. 8 . A (tv left). Extensive fistulazation with posterior urethral stricture and carcinoma.
B (top right). Apparent persistence of fistula after resection of the urethral cancer with primary
end-to-end anastomosis. C (bottom left). Apparent healing of the fistula. D (bottom right). Ure-
November 197.8
throgram several weeks later showing normal urethra.

CANCER
1244
No. 5 TUMORS
OF THE URETHRA - C;mbstald 1245
most frequently in the bulbar urethra, multi- benign urethral meatal condylomas and papil-
ple papillomas most commonly are found near lomas are noted in Figs. 9 and 10. These are
bladder neck and at external meatus.15 Papil- probably not pre-malignant and do not metas-
lomas vary from flat sessile warts to bulky exu- tasize or infiltrate deeply although they are on
berant growths. I n the fossa navicularis, espe- occasion multi-focal.
cially in the presence of infection, they may Diagnosis: More common symptoms include
develop a stratified squamous covering. They itching, irritation, parameatal pain, dysuria,
may be distinguished from condylomas in that discharge, and a feeling of pressure or of a for-
they are more friable and microscopically eign body in the meatus. Patients often notice
have transitional epithelial lining which is not the lesion by simply everting the meatus
overly abundant. There is less leukocytic infil- (Figs. 11 and 12). Papillomas and condylomas
tration than with condylomas, characterized may be grossly indistinguishable and are rec-
by a cauliflower appearance which, in turn, is ognized as mulberry-like reddish-purple pa-
probably secondary to "deep fissuring of acan- pillary lesions just within the meatus.
thotic, hyperkeratotic or para-keratotic surface In only one instance in our series of 18 pa-
layers."3 tients were proximal multiple tumors found.34
There may be a malignant variant of condy- Treatment: Local excision with electro-ful-
loma (Buschke-Liiwenstein Tumor). Lesions guration of base and surrounding areas re-
which have a tendency to spread along the Mains the treatment of choice. Meatotomy
surface and to penetrate deeper tissues were may be carried out to facilitate better visuali-
described by Liiwenstein as "carcinoma-like zation of lesions further within the meatus,
condyloma acuminata."43 He felt that this was but often results in stream spraying. Urethros-
not active infiltration but rather represented copy is mandatory to evaluate involvement of
displaced condyloma tissue as it did not in- proximal urethra.
volve vessels and did not metastasize. For a single reachable lesion I would not
Characteristic histopathologic features of recommend the use of local chemicals such as
FIG. 9. Squamous papillary lesion in a penile urethral meatus. This is histologically indis-
tinguishable from the papillary variety of urethral caruncle (H & E, ~ 5 0 ) .
FIG. 10. Well-differeniated epidermoid cells (keratinocytes), with tonofilaments and some
glycogen connected by desmosomes (~2400).
thiotepa or Podophyllin although the latter metastases, and both died within less than 8
may be useful on occasion. Its value to pre- months. None of these patients had inguinal
vent recurrence is not documented. Recur- lymph node dissection. Partial amputation
rence is extremely low. We have seen only 1. is the treatment of choice for these squamous
One of the reasons for favorable prognosis re- cell lesions.45 Riches and Cullen reported
lates to the fact that early detection is possible inguinal node metastases in 50% of distal
and that a better chance of complete excision urethral tumors.64
exists.15 These are readily managed by partial penile
More proximal intraurethral lesions consti- amputation with or without urethrostomy de-
tute another problem. Halverstadt and Parry pending upon remaining urethral length.
described massive involvement of the urethra. Groin dissection is indicated if suspicious
They recommended use of thiotepa at nodes are palpable. If fairly large nodes are
weekly intervals. Slow and steady regression of felt even preliminary biopsy is not indicated,
lesions was reported within 3 months until as chance of malignancy is great. I have had
only a few distal urethra condylomata re- no experience with radiation therapy for these
mained and these were managed by electro- lesions, but feel that this modality would not
coagulati~n.~~ be preferable in view of almost predictable
We have not had to perform partial ampu- urinary problems.
tation for any of the benign distal urethral le-
sions. THEFEMALEURETHRA
Malignant tumors of the distal urethra: T h e female urethra is divided into 2 areas,
Mandler and Pool described 10 patients with the distal third and the proximal two-thirds.24
distal urethral tumors of whom 7 had sur- T h e histology of these areas, and a diagra-
gery, 3 were subjected to palliative radiation, matic sketch of tumor types arising therefrom,
and 1 had only a biopsy.45 I n this series 2 are seen in Fig. 13.
patients had large ulcerating inguinal node Tumors have been classified as “Anterior”
No. 5 TUMORS
OF THE URETHRA* Grabstald 1247
Fxc. 11. External

urethral meatal papil-
loma.
when limited to the distal third of the ure- For these reasons, the designation “entire”
thra, and “entire” when more or other than was selected when the lesion was not clearly
the anterior third is involved.24 As emphasized limited to the distal urethra. Since our 1966
in our original paper, the tumor may be local- report we have seen 17 additional patients,
ized to the posterior or middle portions of the bringing the total to 96, including 35 anterior
urethra, but it is extremely difficult, particu- and 61 entire tumors (Table 1).
larly from reviewing old records, to rule out Incidence: The first series of female ureth-
involvement of other portions of the urethra. ral tumors reported was that of Wasserman in
For practical purposes, in terms of therapy, 1895 who collected 24 cases.83 McCrea had col-
this classification seems reasonable. Some of lected 546 cases in his review of 1952PO In that
the tumors, mostly posterior, were large or series were included 504 carcinomas, 23 sarco-
had invaded bladder and occasionally vagina. mas, and 19 melanomas. By 1970, Zeigerman
FIG. 12. External urethral meatal papilloma.
and Gordon had collected 768 cases of pri- our series is noted i n Tables 2 and 3. T h e ma-
mary female urethral malignancies.90 jority of patents were seen between age 50 and
Urethral tumors are more common in 69. There are 82 Caucasian and 14 Negro pa-
women than in men. They are reported as tients.
4:179 to 10:160 more common in women. I n Histopathology: T h e pathologic tumor
the latter series there were 132 female and types in our series are noted in Table 1.
only 10 male urethral tumors. I n our experi- There were 67 patients with squamous cell
ence the ratio of female to male urethral tu- cancer, 18 with adenocarcinoma, 5 with mela-
mors is 5: 1. T h e age and racial distribution in noma, 1 with lymphosarcoma, and 5 with mis-
FEMALE URETH RA
Site Histology Tumor
Transitional FIG. 13. The female

urethra. Histology and
Epidermoid tumors derived from
areas indicated.
Squamous
Glands Adeno
Muscle Sarcomas
Ca runcle
No. 5 OF THE URETHRA
TUMORS - Grabstald 1249
cellaneous tumor types. There were 2 benign TABLE1. Tumor Types and Location in Female
tumors, one fibroepithelial papilloma, and Urethra
one fibrosing leiomyoma. These figures are Type Anterior Entire Total
quite similar to those in another series of 92 Epidermoid 22 45 67
cases, which included 64 squamous cell, 19 Adenocarcinoma 6 12 18
transitional cell, 4 adenocarcinomas, and 1 Melanoma 3 2 5
melanoma and “no histology reported” in 4.60 L ymphosarcoma 1 1
In a paper emphasizing the fact that carun- Miscellaneous - 3
-
2
-
5
cles may be mistaken for malignant tumors, of TOTAL 35 61 96
394 cases reported there were 356 caruncles.de
Our series, and most, do not include carun-
cles. tive paraaortic nodes lived 61 months follow-
In most series tumor grade is not men- ing diagnosis though she still died with dis-
tioned. I n our report, carcinomas of the ure- ease (Table 4). Of the 6 patients with adene
thra were of low grade when the apterior ure- carcinoma, 2 had definitely positive external
thra was involved, and grade was slightly iliac nodes, and in 1 there was a question of
higher when the entire urethra was node involvement, but this was difficult to as-
involved.24 certain because of the large nature of the lo-
Lymph node metastases: In one series, 35% cally inoperable mass (Table 5). None of these
of patients had clinically significant lymph adenocarcinoma patients with positive nodes
nodes at first visit, and of the treated cases, were cured, regardless of treatment.
15% subsequently developed secondary Distant metastases: The most common site
nodes.60 I n 2 other series, 47% and 50% of pa- of distant metastases are lung, liver, bone, and
tients had enlarged glands when first seen.76~6~ brain. Distant metastases do not seem to corre-
In our original series there was clinical evi- late positively with lymph node metastases.
dence of inguinal node metastases specifically Distant metastases were more common in pa-
recorded in 25 of 79 patients at some time tients with adenocarcinoma.24
during the course of the disease. Pathologic Diagnosis: Bleeding, local swelling, dysuria,
examination of these clinically enlarged nodes and frequency are the most common
confirmed the presence of cancer in 24 of 25 symptoms.60 In our series, between 5 1% ’ and
patients. This would indicate the fact that vir- 63% had dysuria, bleeding, and frequency.
tually all palpable nodes are abnormal.24 In Four had vaginal fistulas, and in 4 it was an
the overall series, 22 of 79 patients (28%) had incidental finding. Two patients previously
histologic proof of inguinal node metastases. had a diagnosis of car~ncle.~*
Information is a bit more difficult to obtain Treatment and results: As emphasized pre-
about pelvic lymph node status because node viously, therapy is based primarily on tumor
dissection is not systemically carried out. In 26 stage and to a lesser extent on pathologic type
of 79 patients, metastatic nodes were found in and grade.
13, although the incidence is likely higher.24 Among the more common surgical proce-
Among the 17 patients added to our earlier dures performed were partial urethrectomy,
series, there were 6 of 8 patients with epider- total urethrectomy, and various exenterative
moid carcinoma who had had positive lymph procedures. Radiation therapy included exter-
nodes (Table 4). The important fact is that 2 nal, interstitial, and intracavitary tech-
with positive nodes are alive over 5 years later niques.24 Between the years 1926 and 1938,
without evidence of disease. A third with posi- radiation therapy was the treatment of
TABLE
2. Age Distribution of Female Urethral Tumors
TY Pe 21-34 35-39 40-49 50-59 60-69 70-75 Total
Epidermoid 1 4 12 22 21 7 67
Adenocarcinoma 1 4 7 5 1 18
Melanoma 3 2 5
Lymphosarcoma 1 1
Miscellaneous 1 3 1 5
- - - - - - -
TOTAL 2 4 17 32 30 11 96
1250 CANCER
November 1973 Vol. 32
TABLE
3. Types and Race Distribution of Female original 12 patients treated by radiation ther-
Urethral Tumors apy using older techniques, whether or not
Type Caucasian Negro Total lymph nodes contained cancer, all died within
Epidermoid 58 9 67 1 year, except 1 patient who lived 17 months.
Adenocarcinoma 14 4 18 All died of local recurrence; distant metastases
Melanoma 4 1 5 developed in 1.
Lymphosarcoma 1 0 1 Of 4 patients treated with interstitial ther-
Miscellaneous 5 0 5 apy alone ot in combination with external
- - -
TOTAL 82 14 96 therapy, 1 was cured. Since then 2 additional
epidermoid entire tumors have been treated
with radiation therapy only. One treated with
interstitial radon remains without disease 40
choice at our center. Orthovoltage external months following treatment, and 1 treated by
therapy, or interstitial therapy with gold external radiation therapy died 9 months fol-
radon seeds, was used. Interstitial therapy was lowing treatment (Table 4).
used in almost all patients often supple- Of the 14 patients treated solely by surgical
mented with intravaginal sources. methods, 10 died with tumor from 5-33
At the present time only supervoltage tech- months after therapy. There were 2 cures, 1
niques are used. More recent interstitial im- died of uremia 114 months after anterior ex-
plantation techniques have utilized an after- enteration, and 1 remains alive some 10 years
loading technique with iridium as the following surgery.24
source.21 Our results with the treatment of an- During the past 7 years we have not treated
terior and entire urethral tumors treated by squamous cell entire tumors by surgery alone.
radiation only, surgery only, and combina- All patients subjected to surgery have had
tions of radiation and surgery, were reported preoperative radiation therapy. Two patients
in 1966.24T h e 17 cases since that time are are alive for periods of 72 and 85 months
summarized in Tables 4 and 5. after a combination of preoperative external
Anterior: For squamous cell carcinoma lim- radiation therapy and anterior exenteration.
ited to the anterior urethra, we feel that par- One of these patients had bilateral positive
tial urethrectomy is the treatment of choice i f inguinal lymph nodes (Table 4). One patient
it effectively controls local tumor. T h e inci- treated with external, interstitial, and intra-
dence of lymph node metastases is very rare so cavitary radiation therapy, and palliative ileal
that partial urethrectomy alone is enough. conduit, lived for 61 months, although dying
Equally good results have been obtained with of disease.
interstitial irradiation, often supplemented A total of 11 patients with entire adenocar-
with intracavitary and external irradiation. cinoma have been seen, including 5 added to
Our conclusion is that good surgery and care- the original series24 (Table 5). One remains
fully planned irradiation therapy are equally alive 9 years after treatment by partial ureth-
effective in the management of anterior-third rectomy (open and transurethral) for adeno-
urethral lesions. carcinoma, found in diverticulae. One remains
Entire: We now have 45 entire squamous alive with a combination of external radiation
cell cancers in our series, including the 7 pa- . ~ ~the 5
therapy and anterior e ~ e n t e r a t i o n Of
tients added since our original review. T h e patients with entire adenocarcinoma seen
TABLE
4. Female Urethral Tumors Added to Original Series"
Tumor Treatment Survival (mos.)
Pt. Age Type/Stage Nodes Rt Surg Cdis. Ned
1 61 Epid/Entire - 4 40
2 58 Epid/Entire - 4 4 72
3 44 Epid/Entire + 4 9
4 33 Epid/Entire + 4 4 85
5 44 Epid/Entire + 4 4 3
6 38 Epid +Adeno Entire + 4 61
7 54 Epid +Adeno Entire + 4 4 19
8 66 Epid/Ant + 4 4 72
No. 5 TUMORS
OF THE URETHRA - Grabstald 1251
TABLE
5. Female Urethral Tumors
Tumor Treatment S_urvival (mos.)
Pt. Age Type/Stage Nodes Rt Surg Cdis. Ned
9 68 Adeno/Entire + 4 4 Lost to follow-up
10 52 Adeno/Entire + 4 1
11 50 Adeno/Entire ? 4 5
12 52 Adeno/Entire - 4 5
13 53 Adeno/Entire - 4 4 17
14 21 Adeno/Ant - 4 5
15 61 Melanoma/Ant - t/ 4 84
Benign Tumors
16 58 Leiornyo/Ant - 4 20
17 66 Fibroepith/Ant 4 25
Papilloma/Ant
since then, 2 had positive lymph nodes and 1 since the numbers are so small. Epidermoid
may have had positive nodes, althsugh the cancer limited to the anterior third of the ure-
size of the locally inoperable mass made node thra is best treated by surgery only, although
involvement difficult to evaluate. Regardless more modern radiation therapy methods are
of treatment, all have died with disease (Table equally effective.When epidermoid cancer in-
5). volves the entire urethra, i t would appear that
carefully given preoperative radiation therapy
DISCUSSION combined with good exenterative surgery is
the treatment of choice. Four of 15 patients so
The 96 patients seen here represent the treated are alive and free of disease over 5
largest series reported from any single institu- years. The figures are too small although it
tion, to date. would appear that the results with adenocarci-
Proper therapy is predicted on accurate di- noma are about the same and probably a bit
agnosis, and proper grading and staging of better. T o be noted is the fact that one pa-
tumor. In our previous report we proposed tient with a melanoma limited to the anterior
systematic classification to include all possible third of the urethra is alive and well 7 years
tumor stages and grades. In addition to the after preoperative radiation therapy and an-
simple division of tumors into 2 groups, anter- terior exenteration.
ior and entire, a more complicated staging sys- Zeigerman described 27 patients cured of
tem was proposed as tumors were classified cancer of the entire urethra?O Of this group,
into 5 stages, 0, A, B, C, and D.24 14 had various types of radiation therapy,
A summary of our patients who survived 5 mostly radium, and were reported as alive at
or more years free of disease is noted in Table least 5 years after treatment. Thirteen were
6. Twenty three of 84 patients (27%) survived treated by various surgical methods including
over 5 years free of disease. This included simple excision, partial urethrectomy, or radi-
both the squamous cell and adenocarcinoma cal hysterectomy. The average survival rate
and the melanoma groups. Miscellaneous tu- was 8 years for the radiation treatment group
mors, those not treated, or those treated with and 11.6 years for the surgicaI treatment
miscellaneous methods, are not included. g1-0~p.90
These figures are somewhat deceiving and are Radiation therapy was emphasized in the
unfavorably biased, as some patients are still treatment of carcinoma of the female urethra
alive and free of disease, though still not at by Antoniades.1 He indicated that carcinoma
risk, as they were seen and treated less than 5 of the meatus is best treated by interstitial
years ago. It is also unfavorably biased in that gamma-ray therapy in dosages between 5,500
3 patients were alive over 5 years even though and 6,000 rads. Surgical excision or fulgura-
they died with disease. These 3 patients in- tion of meatal lesions should be followed by
cluded one each of squamous carcinoma, ad- interstitial radiation therapy when there is a
enocarcinoma, and melanoma. question of residual disease. He emphasized
As one reviews the Table of 5-year survi- the fact that tumors of the entire urethra
vors, only generalizations are permissable carry a serious prognosis and should be
TABLE6. Summary of Five or More Years Survivors of All Female Urethral Tumors
Treatment Total 5 + yr. Survivors
Type Stage Rt Surg pts. No. %
4 10 3 30
Epid 4nt d 9 7 77
d d 1 1 100
d 14 1 7
Epid Entire d 14 2 14
d d 15 4 26
d 2 0 0
Adenoca Ant d 1 1 100
d d 2 1 50
d 3 0 0
Adenoca Entire d 3 1 33
d d 5 1 20
Melanoma Ant d 3 0 0
Melanoma Ant d d 1 1 100
Melanoma Entire Local + cyrosurg 1
-
0
-
0
TOTAL 84 23 28%
treated by both external radiation as well as cell cancer of the prostatic urethra; 2. squa-
interstitial radium techniques. Treatment of mous cell cancers of the membranous urethra;
regional nodes should be reserved for demon- and 3. tumors of the meatal and parameatal
strated disease either on clinical examination areas, the latter seen for the most part in the
or by lymphangiography.1 I also favor groin young adult. Primary transitional cell cancer
dissection only when there is palpable disease. of the prostatic urethra is characterized by the
Taggart et al. recommended that localized fact that it is very rarely diagnosed at an early
anterior urethral disease be treated by intersti- stage and by the complete resistance to endo-
tial implantation. Open bladder implantation crine therapy. There are no characteristic
was emphasized as being essential for proper symptoms of this lesion. Except for those le-
placement of the needles. We have had n o ex- sions which are superficially infiltrating and
perience with cystotomy utilized to facilitate which may be cured by transurethral resec-
interstitial implantation. T h e risk of tumor tion, the results with ablative surgery, whether
spillage might be significant. or not preceded by radiation therapy, are
Pointon and Poole-Wilson suggested surgery quite poor. T h e usually extensive nature of
only when previous treatment failed or was the tumor in this location makes ablative sur-
contraindicated. They indicated that the role gery, regardless of extent, very difficult and
of surgery should be: 1. to salvage patients the results are quite poor.
with recurrent tumors following radiation Carcinomas arising in the bulbo-membra-
therapy or excision; 2. for primary treatment nous and deepposterior urethra are charac-
of patients with deep urethral lesions causing terized by a preceding history of infection,
urinary obstruction; and 3. treatment of radi- trauma, and instrumentation. Very often a
oresistant tumors, such as melanoma and slow growth pattern is demonstrated between
sarcoma.60 Our material does not support this initiation of symptoms and diagnosis. Regard-
view as cures have been achieved with combi- less of the extent of ablative surgery, the re-
nations of irradiation and ablative surgery sults with treatment have been extremely
when the entire urethra was involved and by poor.
either method alone in properly selected an- Those lesions in the distal penile urethra,
terior lesions. but not at the meatus, are for the most part
readily cured by excision with appropriate
SUMMARY
AND CONCLUSIONS margins. Five of 7 patients with pendulous
urethral tumors were rendered free of disease
T h e three most important tumors involving by either partial amputation or total amputa-
the male urethra are: 1. primary transitional tion.
No. 5 TUMORS
OF THE URETHRA
* Grabstdd 1253
Urethral nieatal tumors are either papillo- means of radiation therapy, including intersti-
mas or condyloma acuminata. These are be- tial and external. Entire urethral tumors are
nign and virtually limited to men in the best managed by preoperative radiation and
20-40-year age group. They are usually effec- anterior exenteration. Ninety-six women with
tively managed by local excision and fulgura- urethral tumors are reported. Proper therapy
tion. More proximal urethral involvement is predicated on accurate diagnosis and proper
should be ruled out by urethroscopy. .
grading and staging of tumor. A staging classi-
Tumors of the female urethra are divided
into those involving the distal third and fication is proposed based upon depth of pene-
termed “anterior” and those involving more tration of urethral wall and upon invasion of
or other than the anterior third and classified surrounding tissues, as well as upon the pres-
as “entire.” For squamous carcinoma limited ence of metastatic disease. T h e presence of
to the anterior urethra, partial urethrectomy deep pelvic nodes is an ominous finding. Rad-
is the treatment of choice, but similarly good ical groin dissection is recommended for those
results may be obtained with more modern patients with palpable disease.
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No. 5 TUMORS
OF THE URETHRA Grabstald - 1255
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TUMORS OF T H E URETHRA I N MEN

G ROSSLY A N D MICROSCOPICALLY, THE URE-

T h e major urethral divisions, the histology PROSTATIC TUMORS

FIG. 1. Gross anatomy of male

The duration of symptoms varies greatly. tients): and 2. Bulbo-membranous or Prostatic

ment of skin of peri-

neum and scrotum.

throgram several weeks later showing normal urethra.

Fxc. 11. External

FIG. 12. External urethral meatal papilloma.

Site Histology Tumor

Transitional FIG. 13. The female

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