Primary Carcinoma of the Male Urethra

Primary Carcinoma of the Male Urethra

Vol. 96, July Printed in U.S.A. THE JOURNAL OF UROLOGY Copyright © 1966 by The Williams & Wilkins Co. PRIMARY CARCINOMA OF THE MALE URETHRA JOHN I...

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Vol. 96, July Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1966 by The Williams & Wilkins Co.

PRIMARY CARCINOMA OF THE MALE URETHRA JOHN I. MANDLER

AND

THOMAS L. POOL

From the Mayo Clinic and Mayo Foundation: Section of Urology, Rochester, Minnesota

Carcinoma arising in the male urethra, although uncommon, continues to be one of the most difficult and challenging lesions treated by the urologist. More than 250 cases have appeared in the literature1 • 2 since the first case was reported by Thiaudierre 3 in 1834. Various forms of surgical and radiation therapy have been employed4.._surgical treatment ranging from simple excision through radical resection with node dissection and irradiation, from topical and localexternal to regional application. Management of tumors of the distal part of the urethra by partial amputation of the penis has yielded survival rates of about 50 per cent. Tumors of the deep portions of the urethra, which comprise between one half and two thirds of most series, have much graver prognoses. 5 In 1947, Zaslow and Priestley6 reported on the experience at the Mayo Clinic for the period from 1910 to 1945 in the treatment of this malignancy. Because of the small size of the series, 25 cases, the authors did not attempt to evaluate the various forms of therapy, but they noted a more favorable prognosis for distal lesions. It is the purpose of the present study to add to that review the experience at the Mayo Clinic in the management of these lesions from 1945 through 1964.

membranous; and 3) prostatic. The type of treatment employed, especially surgical, remained somewhat constant within these groups. Distal. Ten patients, averaging 63 years of age, presented with tumors of the distal portion of the urethra. Seven had urethral bleeding for from 3 days to 15 years as the initial symptom. Of these, three had associated obstructive symptoms. The three having no urethral bleeding complained of obstruction and a persistent purulent or watery urethral discharge. None of the patients had a history of urethral stricture, although one, aged 78, had had gonorrhea as a youth. Bulbomembranous. All 20 patients having tumors involving the bulbomembranous region of the urethra presented with urinary obstructive symptoms of various durations. Perineal pain and swelling, often with associated spontaneous perinea! fistula, were noted in 13 cases. Five patients had hematuria or a bloody urethral discharge associated with difficulty in micturition. Six patients gave a past history of urethral stricture requiring periodic dilatation-postgonococcal in 5 cases and secondary to a straddle injury in one. Ten other patients, only one of whom had a previous history of urethritis, had "strictures" requiring dilatation as frequently as every 4 weeks for periods of up to 1 year. Carcinoma had been suspected and confirmed in 3 of these 10 cases, while it remained unsuspected in the other 7 at the time of the first visit to this clinic. Twentyfour operative procedures-urethrotomy, transurethral resection, and incision and drainage of perineal abscess being the most common-had been performed elsewhere in 13 of the cases, including 3 of the 10 just discussed. The final operative procedure established the diagnosis of tumor in 8 cases. It remained unsuspected in the other five. The average age of patients in this group was 56 years. Prostatic. Seven patients, who averaged 60 years of age, were found to have carcinoma limited to the prostatic urethra. Four sought advice because of gross hematuria, one of whom had prostatic calculi and recurrent prostatic abscess and two of whom had associated irritative symp-

MATERIALS AND METHODS

The case records of 37 male patients having primary urethral carcinoma were studied. Three groups were recognized according to the site of the tumor: 1) distal-involving the meatus, fossa navicularis, and pendulous urethra; 2) bulboAccepted for publication August 9, 1965. 1 Marshall, V. F.: Radical excision of locally extensive carcinoma of the deep male urethra. J. Urol., 78: 252-264, 1957. 2 King, L. R.: Carcinoma of the urethra in male patients. J. Urol., 91: 555--559, 1964. 3 Thiaudierre, P. D.: Quoted by Hotchkiss and Amelar. 8 4 Flocks, R. H.: The treatment of urethral tumors. J. Urol., 76: 514-526, 1956. 5 Riches, E.W. and Cullen, T. H.: Carcinoma of the urethra. Brit. J. Urol., 23: 209-221, 1951. 6 Zaslow, J. and Priestley, J. T.: Primary carcinoma of the male urethra. J. Urol., 68: 207-211, 1947. 67

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MANDLER AND POOL TABLE

1. Tumors of the distal part of the urethra Tumor

Case

1 2 3 4 .5 6 7 8 9 10

Age, Yr.

30 37 61 56 63 74 78 73 78 76

Survival*

Treatment

Excision, fulguration Excision, fulguration Excision, fulguration Partial penectomy Partial penectomy Partial penectomy Partial penectomy Biopsy, radiation Biopsy, radiation Biopsy

Cell Type

Grade

Squamous Transitional Transitional Squamous Squamous Squamous Squamous Squamous Squamous Squamous

2 1 1 2 3 2 2 2 3 2

20 yrs. 2 yrs. 10 yrs. 3 yrs. 18 mos., then lost to followup Died, 25 mos. (cause unknown) 10 yrs. Died, 6 mos. Died, 8 mos. Died, 15 mos.

* Patient living at time of followup unless otherwise noted.

tmns. Two other patients gave long past histories of inflammatory disease~prostatitis and recurrent cystitis. The seventh patient had had a prostatic resection 4 years earlier for benign prostatic hyperplasia. None had a hi,;tory of urethral stricture. RESULTS

Distal urethral tumors. Table 1 gives data relative to cases in this group. Seven patients were treated surgically, while two (cases 8 and 9) received palliative treatment with radiation. Patients 8 and 9 had large ulcerating metastases of the inguinal lymph nodes. Patient 10 had a large fixed pelvic mass and was treated with suprapubic cystosto1ny. No inguinal node dissection was done, and this seemed to have no adverse effect on survival. It is doubtful if such therapy would have altered the course of the only 2 patients who had positive inguinal metastases on clinical examination. Radiation when used had no noticeable effect on either the primary lesions or the metastases. The two papillary lesions were transitional cell carcinomas. Squamous carcinoma, grossly less exophytic, was usually invasive. Partial amputation of the penis was the treatment of choice for these squamous lesions. None of the patients whose lesions were considered operable had irradiation as the treatment of choice, as did some of those reported on in the previous report from this clinic. Bulbomembranous iirethral tumors. Table 2 gives pertinent data for patients in this group. Two patients had no treatment. Excisional surgical procedures were performed in 7 cases (11 through 17). One patient (case 12) had lived for

17 months, at the time of followup evaluation, without evidence of tumor; and one (case 14) had a local perineal recurrence and pelvic pain 12 months after operation. Four patients (cases 11, 13, 15, 17) survived only an average of 10 months after operations which had removed the tumor with adequate margins. Radiation therapy was used as the primary form of treatment in 11 cases including case 30 which was treated elsewhere. In two (cases 20 and 22) a regression of an extensive perinea] mass was effected, but this form of treatment had no notable effect on the remaining 9 cases. Illustrative cases: A 56-year-old osteopath (case 12) noted difficulty in voiding and was treated with urethral sounds. He had no history of previous urethral inflammation or trauma. A periurethral abscess developed and resolved slowly. Two transurethral biopsies were "suspicious but not diagnostic" of carcinoma. He sought no further treatment until he came to this clinic because of marked obstruction 7 months after the onset of his symptoms. A large perineal mass was present. A cystoscopic examination was done and squamous carcinoma of the urethra observed and biopsied. Laparotomy revealed no visceral or nodal metasta~es. The patient was emasculated, and suprapubic cystostomy was performed. A tumor measuring 8 cm. in its greatest diameter was removed. The urethra was closed at the prostatic apex where it was uninvolved. Radiation-5,700R to the pelvis via two portals and 3,SOOR to the para-aortic regionwas given several months postoperatively. There was no evidence of tumor 17 months after the operation.

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F'l{B!AJW CARCI:'\OJ\IA OF MALE URETHRA TABLE

2. Tumors of the bulbomernbranous u.rethra Tumor

Treatment

Cell Type

ll 12 13

14 15

16

17 l8 19

20 21 22 23

24

25

26 27 28

29 30

.fl

Emasculation, cystoprostatectomy, ureterosigmoidostomy (i(j Emasculation, suprapuhic cystostomy, radiation Emasculation, suprapubic cys58 tostomy, bilateral excisiotl of inguinal and iliac nodes [55 Emasculation, prostatectomy, suprapubic C)'Stostomy 58 Emasculation, cystoprostaiectomy, ure1 erosigrnoidostomy, bilateral excision of inguinal nodes 6:3 Emasculation, suprapubic cystostomy Partial urethrectomy, radiation 50 24 Biopsy, radiation (radical operation elsewhere 4 mos. later) ±9 Suprapubic cystostomy, radiation .50 Supra pubic cystostomy, radiation 8uprapubic eystostomy, rndi57 ation Suprapubic cystost.omy, radi66 ation 71 Suprapubic cystostomy, incision and drainage of perinea! abscess, radiation Biopsy, radiation (suprapubic 55 c:vstostomy elsewhere 4 mos. earlier) (lO Biopsy, radiation fl:3 Biopsy, radintion Biops)·, radiation 6:5 37 ' Biops:v (refused further therapy) 61 Biopsy Biopsy (radiation and perinea] 71 ureihrostomy 22 mos. earlier)

Squamous

3

Died, 12 mos.

Squamous, transitional cell Squamous

3

17 mos.

2

Died, 8 mos.

Squamous

1

Squamous

2

12 mos. (perinea! rence) Died, 10 mos.

Squamous

2

11 mos., lost tu followup

Squamous Adenocarcinoma

2 2

Squamous

2

Died, 12 mos. 10 mos. (pulmonary metms tasis) Died, 9 mos.

Squamous

2

Squamous

4

Squamous

3

Squamous

4

Died, 31 mos. (regrnssion of perinea! mass) Died, 7 mos.

Adenocarcinoma

2

Died, :57 mos.

Squamous Squamous Squamous Squamous Transitional cell Squamous

3 2

Died, 4 mos. 10 mos., lost to folJowup Died, 10 mos. 10 mos., lost. to followup Died, 3 mos. Died, 24 mos.

A. 58-year-old mechanic (case 15) required periodic urethral dilatation for a straddle injury sustained in his childhood. A. Yrnekly need for such treatment developed coincident with a region of perinea! induration. Open biopsy showed that the induration resulted from squamous cell carcinoma, and the patient was referred to the 11/layo Clinic for treatment ..A movable perinea! mass was present. At cystoscopy, a tumor was seen extending from the external sphincter to the

2

2 2

2

recur-·

Died, 35 mos. (marked re gression of perinea! mass) Died, 10 mos.

penoscrotal angle. Laparotomy revealed no visceral metastases. Bilateral ureterosigmoidostomy, cystectomy, prostatovesiculectomy, emasculation, and bilateral excision of superficial and deep inguinal nodes were done. The tumor measured a by 3 by 5 cm. and had been removed with aclrquate margins. The nodes-inguinal, ohturator, and external iliac-were free of metasta~is. A small perinea! sinus developed, and the patient, experienced pelvic pain. Four months after the

70

;HANDLER AND POOL TABLE

3. Tumors of the prostatic urethra Grade of

Case

Age, Yr.

Treatment

31

.50

32 33 34 35 36 37

,52 65 54 52 68 82

Cystoprostatectomy and ureterosigmoidostomy TUR and radiation TUR and radiation TUR TUR TUR TUR

Survival

Tumor*

4

Died, 25 mos.

3

3 yrs., lost to followup Died. 11 mos. Died, 7 yrs. 40 mos. 18 mos. 7H yrs.

3 2

1 3

1

* All tumors of the prostatic urethra were of the transitional cell type.

operation, curetting of the sinus tract yielded carcinoma. The patient died 5 months later. A 49-year-old salesman (case 19) complained of perineal discomfort and slowing of his urinary stream. He was treated by means of urethral dilatations every 3 to 4 weeks; and, after 5 months, an internal urethrotomy was performed without relief of his symptoms. A bloody urethral discharge developed. Eight months after the onset of his symptoms he was referred to this clinic for treatment of an intractable stricture. He denied previous urethritis or trauma. Deep periurethral induration was present. A cystoscopic examination showed obstruction by a squamous carcinoma involving the entire bulbomembranous urethra. After suprapubic cystostomy, irradiation of the perineum was instituted. A tumor dose of 8,400R was given, and the mass regressed minimally. Four months later, metastasis had developed to the lungs and bony pelvis. The patient died 9 months after his diagnosis was made. A 50-year-old maintenance worker (case 20) noted perineal discomfort, difficulty in voiding, and occasional urethral bleeding. Prostatic massage gave him no relief during a 1-year period. A perineal mass developed and was biopsied to establish the diagnosis of malignancy. A fistula resulted and increased in size. He was referred to this clinic for further treatment. When first seen, he had a hard, fixed perineal mass with a central fistula. Cystoscopic examination showed a papillary tumor involving the entire bulbomembranous urethra. Biopsy proved it to be squamous cell carcinoma. No inguinal nodes or abdominal masses were present, and a roentgenogram of the chest was normal. A tumor dose of 8,000R was delivered via a perineal port after suprapubic cystostomy. Dur-

ing the following 6 months, the perineal mass resolved and the fistula closed. Di8comfort requiring analgesics persisted. Fourteen months after therapy the mass recurred. On two occasions, biopsy was done but no carcinoma noted. The fistula recurred as a complication. The patient's condition remained unchanged until rapid terminal deterioration and death 35 rnonths after the beginning treatment. Prostatic urethral tumors. Table 3 summarizes data from cases in group 3. In all cases, the tumor cells were of the transitional type. No previous or subsequent tumor of the bladder, ureter, or renal pelvis was found in any of these cases. Open surgical resection was done in case 31 after four previous transurethral resections during a 17-month period had failed to prevent recurrence. This patient died of metastasis 8 months later. In this group of cases, generally, extensive transurethral resection resulted in survival of from 1 to 9 years. Radiation offered no predictable benefit. COMMENT

In the reports on carcinoma of the n1ale urethra, a high incidence of antecedent urethral stricture has been noted-between 50 per cent and 88 per cent in the various series. 7 • 8 Postinflammatory or post-traurnatic strictures are usually encountered in the bulbomembranous urethra. In this series, the lowest reported incidence of such strictures was noted-30 per cent for tumors of the posterior urethra and 16 per cent for those of the entire series. Dilatation and 7 Dean, A. L.: Carcinoma of the male and female urethra: Pathology and diagnosis. J. Urol.,

75: 505-513, 1956. 8 Hotchkiss, R. S. and Amelar, R. D.: Primary carcinoma of the male urethra, J. Urol., 72: 11811191, 1954.

PRBJARY CARClNOJ\IA OF MALE URETHRA

incision of what proved to be a neoplasm were far more common. The development of a "stricture" in a middleaged or elderly man with no previous history of nrethral especially an obstrnction which bleeds easily and requires increasingly frequent dilatation, should arouse suspicion with regard to 1u·ethral malignancy. Only an awareness that the symptoms of such benign cli.seases as urethral urethritis, prostatiti~, and prostatic enlargement arc also those of urethral maligrrnncy can lead to early diagrnJsis. This, in turn, results in longer survival. For instance, one patient having a distal urethral carcinoma was seen 4 months after the on~et of symptoms and has .lived 10 years since appropriate treatment, and a patient having carcinoma of the prnxirnal urethra was seen as early as 7 months after his symptoms began and has remained tumor free for 1 year si nee treatment. In establishing the diagnosis, biopsy of tissue protruding into the urethral lumen or of susareas of the urethral ,mil was performed 'in most cases, The Papanicolaou examination -of the urinary sediment and of urethral 'Washings failed to give a positive diagnosis in 2 cases. King 2 found this test to be positive in f(llll" of his cases and suggested that it be used as a diagnostic airl if the disease is suspected. Our limited experience has failed to support his suggestion. The common cell type throughout the series was cquamous carcinoma, and the tnmor was usually grade 2 or 3. Transitional cell carcinoma, as expected, arose in the prostatic urethra and was 8een in two papillomas of the distal urethra, which had undergone malignant degeneration and in one instance of bulbo.membranous involvement. Two patients had adenocarcinoma and both of them had a history of refractory nonspecific urethrifo. Scott and Barelare 9 suggested that adenocarcinoma may follow metaplasia of the urethral epithelium and that it can be differentiated from tumorn arising from the glands of Cowper and Littre. A biopsy ta.ken 3 months before a second one which was positive for tun10r "as studied ,vith this in mind. Only non-specific inflammation was noted; there was no evidence of metaplasia of the urothelium. One would surmise that this tumor arose primarily from the deep urethral glands.

r

9

cinoma 1()52.

z. and l3arelare, B.: Adenocarthe male urethra. ,L Urol, 68: 311-319,

:E. Y.

71

No correlation between the degree of differentiation of the tumor and the prognosis or response to radiotherapy could be found fot· the squamous cell tumors. There ,vas such a conelatio11, however, for transitional cell carcinomac<. Two pa. tients with grade 1, transitional cell lesions of the distal urethra have lixed for 2 and l O years siuu, treatment, and one patient whose grade J, trans1iional cell tumor arose in the prostatic urethra has lived for 7H years, Distal methra.l tumors have the best Partial amputation of the penis offers the best chance for cme of infiltrating lesions, while local excision may suffice for non-infiltrating lesion,,; ho,vever, frequent followup examirmtions shoulcl Le made after local excision. )\.lthougb Richc,s and Cullen 5 noted inguinal node metastasis i11 50 per cent of their cases and recommended treat ment by excision or irradiation, the findings and results in our cases fail to support this. Node di~section ,ms not employed, and radiation failed to alter the downhill course. After partial penectomy, no recurrence of tunwr in the urethral stun1p was observed, and ead1 opera.tor stressed that a tumor-free margin of at least 2 cm. was achieved at operation. The rnsul.ting penile stump was adequate to permit directing of the urinary stream and no perineal urethros tomies were constructed. One troublesome meatal stricture followed local excision and required periodic dilatation. A plastic dilator was med as needed to keep the mea.tns patent. Regardless of the degree to which radical smgi-· cal therapy was extended in the treatment. of deep urethral tumors, it did not give results with respect to survival, in this series of cases. J\Iarshall,1 employing radical excision in the treatment of 5 cases, achieved a stuvival of 80 per cent. Of the 6 cases so treated a.t this clinic, only one is tumor free l year after operation. The direct access of tbc tumor to rich venous and lymphatic drainage and the manipulation by instrumentation when a malignant tumor is unsuspected early in the course of the disease probably lead to early Yisceral and pulmonary spread; micrometasta,es probably are present at the time of evaluation for radical curative operation. Radiation therapy, in this series, has resulted in cornparable to superior survival figures and will continue to be used for palliation and as an adjunct to operation. l\fost. of our patients who were treated by diversion or biopsy were found to be inoperable at the fone of

72

MANDLER AND POOL

their first visit to this clinic. Inoperability was based mainly on the degree of local extension, for few patients presented with recognizable gross metastasis. Prostatic urethral tumors respond much the same as do transitional cell tumors of the bladder, the prognosis varying with the degree of differentiation and the degree of infiltration. These tun10rs seemed to be the most common when the present study was undertaken; however, it was soon apparent that most of them were implants or extensions of neoplasms occurring more proximally in the urinary tract. Of 30 patients having such secondary urethral tumors, 22 died of their disease, 3 were lost to followup evaluation and 5 were alive 3 to 8 years after appropriate surgical and radiation therapy. SUMMARY

We reviewed the case records of 37 men who had primary urethral carcinoma and who had been men at the Mayo Clinic from 1945 through 1964. There was often a long interval of misdirected treatment before the correct diagnosis was made. Interestingly, the incidence of pre-existing urethral stricture was low.

Therapy varied with the site of origin of the tumor, the extent of the tumor, and the age and general condition of the patient: Of 10 patients having lesions of the distal part of the urethra, 3 had local incision, 4 partial penectomy, and 3 palliative radiation; of 20 patients having lesions of the bulbomembranous urethra, 2 had no treatment, 7 excisional operation, and 11 radiation; of 7 patients having lesions of the prostatic urethra, 1 had extensive operation and 6 had transurethral resection~with radiation in 2 cases. Local excision or partial penectomy proved to be adequate treatment for carcinoma limited to the distal portion of the urethra. For lesions of the bulbomembranous urethra (54 per cent of our cases), radiotherapy gave results comparable or superior to those of radical excisional operation: Regression of perineal lesions occurred in 2 of 11 cases in which radiation was used, and the one patient living and apparently free of disease at the time of the study had had radiation in addition to operation. Extensive transurethral resection for lesions of the prostatic urethra resulted in survival for 1 to 7½ years, but radiation offered no predictable benefit.