Carcinoma of deep male urethra

Carcinoma of deep male urethra

CARCINOMA JOHN H. FARRER, OF DEEP MALE URETHRA M.D. ANDRE1 N. LUPU, M.D. From the Department of Surgery, Division of Urology, UCLA School of Medicin...

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CARCINOMA JOHN H. FARRER,

OF DEEP MALE URETHRA M.D.

ANDRE1 N. LUPU, M.D. From the Department of Surgery, Division of Urology, UCLA School of Medicine, Los Angeles, California

ABSTRACT-Carcinoma of the deep male urethra is a rare disease. Conservative measures yielding dismal outcomes were standard until 1957, with the report of an 80 per cent five-year survival rate after radical surgery. To assess the value of this surgery, we reviewed all cases of carcinoma of the deep male urethra managed at UCLA Medical Center and its affiliated hospitals between 1952 and 1980. Of the patients managed with radical surgery, 1 died of a myocardial infarction between staged surgical procedures, and 5 died of their disease between twelve and fifty-two months postoperatively (mean survival, 26 months). There were 2 long-term disease-free survivors, yielding a survival rate of 25 per cent. We have also compiled the results of all major series dealing with deep urethral carcinoma published subsequent to the 1957 report. This review of the literature supports the concept that radical extirpative surgery is mandatory in the management of carcinoma of the deep male urethra.

Primary carcinoma of the male urethra is an uncommon disease, accounting for less than 1 per cent of all urologic malignancies. 1-3Since its initial description in 1834, approximately 400 cases have been reported.4 The site of the lesion is a key prognostic indicator4m6 and is the primary determinant of therapy.4,7,8 Lesions in the pendulous urethra are more amenable to extirpative surgery than are the deep urethral lesions.g Deep urethral carcinoma occurring in the prostatic and bulbomembranous urethra tends to be diagnosed after a long symptomatic interva14sg and requires extensive surgical procedures to achieve local control.‘O Evolution of the surgical management of deep urethral carcinoma has paralleled the development of radical surgical techniques in general. Starting in the 195Os, the principles of radical excision were successfully applied to locally extensive, deep urethral lesions.’ While subsequent series have emphasized the generally poor outcome of any therapeutic modality, the key role of radical surgery in managing deep urethral carcinoma has been reiterated by many authors,3.8-1’ yet questioned by others.r2,r3

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In an attempt to define the role of radical surgery more clearly, a retrospective analysis of all cases of carcinoma of the deep male uret.hra managed at UCLA Medical Center over the past twenty-eight years is presented. Material and Methods The tumor registries of UCLA Medical Center and its affiliated hospitals (Wadsworth Veterans Administration Hospital, Sepulveda Veterans Administration Hospital, and Harbor/UCLA Medical Center) were searched for all entries of primary male urethral carcinoma during the period from 1952 to 1980; 22 such cases were recorded, although only 10 are included in this report. The basis for exclusion is the location of the malignancy distal to the penile suspensory ligament, or a history of previous urothelial malignancy, The ages of the patients at the time of presentation ranged from thirty-two to seventy years (mean, 56 years). The average interval from the onset of symptoms to diagnosis was seven months (range, 1 to 12 months). Past urologic

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TABLE I.

Age

Histol.

Tumor Grade

Specijic data on 10 cases of deep urethral carcinoma UCLA Medical Center from 1953 to 1980 Stage

Surgery*

Therapy Radio.

Chemo.

managed

at

-NodesI P

48 70 65

Squam. Squam. Squam.

3 3 2

B D, D1

Rad IB Rad IB Rad IIC

4,500 R 4,000 R No

No Vin. 5FU

+ +

+

61 32

Adeno. Adeno .

. . 1

B C

Rad IB Rad IS

No

No

No

-

57

Squam.

2

C

Rad IIS

No

Adria., BCG No

-

-

62 49 61

Squam. Squam. Squam.

3 3 3

C D1 D1

Rad IIB B C

No

-

-

+ +

+ ..

Died, metas.; local recur., 14 mo Died, metas., 12 mo Died, MI, 8 mo Died, metas., 7 mo

59

Squam .

3

D,

C

6,000 R

+

. .

Died,

No No

No 6,000 R

5FU, Cytoxan 5FU, Cytoxan

-

Outcome

-

NED at 5 yr Died, metas., 17 mo Died, metas. and local recur., 33 mo NED at 12 yr Died, metas., 52 mo

metas.,

KEY: I = inguinal; P = pelvic; NED = no evidence of disease; Squam. = squamous; Adeno. = adenocarcinoma; 5-FU = 5-fluorouracil; Adria. = Adriamycin; BCG = bacillus Calmette-G∈ MI = myocardial infarction. *Rad IB: radical cystoprostatourethrectomy with proximal corporectomy and Bricker urinary diversion Rad IIC: radical prostatourethrectomy with proximal corporectomy and cystostomy Rad IS: radical cystoprostatourethrectomy with proximal corporectomy and ureterosigmoidostomy Rad IIS: radical prostatourethrectomy with proximal corporectomy and ureterosigmoidostomy B: Bricker ureteroileal diversion c: cystostomy

history included 7 with urethral strictures (70%), 3 with venereal disease (30%), 3 with prior urologic instrumentation other than dilatation (30%), and 1 with significant perineal trauma (10 %). At the time of presentation all 10 patients complained of obstructive symptoms. Moreover, 4 had gross hematuria and 1 Other presentations inhad hematospermia. cluded a palpable inguinal or perineal mass, scrotal abscess, and a bloody urethral discharge. Histologically, 8 of the 10 cases were identified as squamous cell carcinoma; the other 2 were adenocarcinoma. Six of the tumors were grade 3 (of 3), 2 were grade 2, and 1 was grade 1; another was not graded. While the single well-differentiated tumor was an adenocarcinema, all 6 of the poorly differentiated tumors were squamous cell carcinoma. Staging was done retrospectively, using the criteria of Ray et al9 as follows: Confined to mucosa only (in Stage 0: situ) Into, but not beyond, lamina Stage A: propria Into, but not beyond, substance Stage B: of corporus spongiosum, or into, but not beyond, prostate

528

3 mo

Vin. = vincristine;

Direct extension into tissue beyond corporus spongiosum (corpora cavernosum, muscle, fat, fascia, skin, direct skeletal involvement), or beyond prostatic capsule Regional metastases including Stage D1: inguinal and/or pelvic lymph nodes Distant metastases Stage Dz: None of the cases was Stage 0 or A. Two patients presented with Stage B disease, 3 with Stage C, and 5 with Stage D. Of the 5 Stage D patients, 4 were Stage Di (regional nodal metastases), and 1 was Stage Dz (distant metastases). All of the Stage D patients had squamous cell carcinoma. Given the twenty-eight-year time frame of the study, various modifications of the overall radical surgical approach were introduced. Although every patient received the same treatment in substance, technical variations did occur. The surgical and adjuvant therapies are detailed in Table I. The key feature of the surgical approach in this series was a prostatourethrectomy, proximal corporectomy, and inguinal and pelvic lymphadenectomy, performed in 7 of the 10 cases. In 4 of the 7 cases,

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cystectomy was also done. Urinary diversion was achieved with a cystostomy (3), ureteroileal diversion (5)) or ureterosigmoidostomy (2). Adjuvant chemotherapy was used in 5 cases, 2 of which were patients deemed inoperable, managed only with radiation and chemotherapy. Both of these patients received 5fluorouracil and cyclophosphamide (Cytoxan) . The 3 other patients underwent postoperative chemotherapy consisting of 5-fluorouracil, vinblastine, doxorubicin hydrochloride (Adriamycin), or bacillus Calmette-G&in (BCG). Adjuvant radiation therapy was employed in 4 cases, 2 of which (as previously mentioned) were inoperable. Of the 2 surgical candidates receiving radiation therapy, 1 was treated preoperatively with 4,500 rad to the perineum, and 1 was treated postoperatively with 4,000 rad to the pelvis. Results Of the 10 patients in this series, 2 were not deemed surgical candidates but were managed palliatively; they had a mean survival time of five months. A third patient died after a myocardial infarction eight months after ureteroileal diversion had been performed, but prior to radical surgery. Of the 7 patients who actually underwent radical surgery, there were no operative deaths, although 5 of the 7 patients eventually died of their disease between twelve and fifty-two months postoperatively (mean, 26 months). These failures all presented with Stages C (3) or D1 (2) disease. Of these 5 patients, 3 received adjuvant chemotherapy. Survival of the subset treated with postoperative chemotherapy was substantially greater than that of patients who were not treated with chemotherapy (mean survival of 34 months versus 13 months). Two local recurrences occurred at nine and thirteen months after surgery; death came five and twenty months, respectively, after the recurrence. A local recurrence was associated with a modestly reduced mean survival time (23 months versus 27 months in the absence of a local recurrence). The only long-term survivors in the series were the 2 patients who presented with Stage B disease, who are alive without evidence of disease at five and twelve years after treatment: 1 had an adenocarcinoma, the other a grade 3 squamous cell carcinoma. Overall survival when correlated to stage indicated a

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100 per cent five-year survival for Stage B, a twenty-six-month mean survival time for Stage C, and a twenty-five-month mean survival time for Stage D. Inguinal lymph nodes alone were histologically involved with tumor in only 1 case. In 2 others both inguinal and pelvic nodes were involved. In no case were pelvic nodes positive in the absence of inguinal nodal involvement. Comment Of our patients the mean age at presentation (56 years) is consistent with other studies,6J4J5 as is the 30 per cent incidence of venereal disease.g,14J5 However, the 70 per cent rate of stricture disease in our patients is much higher than the 35 to 48 per cent rate reported in other large reviews.14,15 Since these reviews included tumors from the entire urethra and our series is limited to deep urethral tumors, the discrepancy in incidence of strictures suggests an association between deep urethral carcinoma and strictures, which has been observed in another report. l2 Moreover, that same report noted that of 16 cases of deep urethral carcinoma associated with stricture, 10 were of recent onset (less than 1 year) or required increasingly frequent dilatation. Two of 7 of our cases (28 per cent) fell into this category, suggesting that the “stricture” was actually the tumor. The signs and symptoms of urethral carcinoma are said to be varied, nonpathognomanic, and nondiagnostic. Yet the 100 per cent incidence of obstructive symptoms in the current study is particularly striking inasmuch as other authors have substantiated this finding in deep urethral carcinomas.r2 The other presentations, i.e., perineal or inguinal mass, hematuria, hematospermia, and bloody urethral discharge, have all been previously described.4-8,g Presentations reported elsewhere but not seen in our series are priapism, penile gangrene, and incontinence.r4 Classically, deep urethral carcinoma is associated with a prolonged symptomatic interval prior to diagnosis. A mean interval of eighteen months (compared to 11 months for anterior lesions) has been reported.g The interval observed in the current study (7 months) is substantially shorter than in other reports but did not appear to influence either the stage at presentation or long-term survival of our patients relative to prior studies.g In fact, others have found no correlation between duration of symptoms and survival .g

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TABLE II.

Author

Compilation

(Institution)

Marshall’ (Cornell) King’ 1 (Johns Hopkins) Mandler and Po01’~ (Mayo Clinic) Mullin et alG8 (Duke) Ray et aZ.g (Memorial Sloan-Kettering) Farrer and Lupu (UCLA)

of results of major series of deep urethral carcinoma (1957-1980)*

Period

-Cases Total

1933-1955

8

0

4

6

2

4

1

20

3

17

0

0

0

1943-1973

5

2

3

1

1

0

(39 Yr) 1940-1970

14

10

4

2

1

1

(39 Yr) 1952-1980

10

8

2

2

2

0

(19yr)

(28 yr) 1933-1980 -

Survival WINEDRad. Surg. Other

3

19Er~64

KEY NED = no evidence of disease. *Due to insufficient data or insufficient

-5-Yr Total

5

19Er9)61

TOTALS

63

-

(&)

(47 yr) follow-up

time,

other

The distribution of histologic types in our study confirms the widely observed prevalence of squamous cell carcinoma in cancer of the urethra (80 per cent of our cases; 62-88 per cent in other series4J.14J6). However, the absence of any cases of transitional cell carcinoma and the 20 per cent incidence of adenocarcinoma are definitely not consistent with the literature, probably representing sampling error inherent in a small population. Other authors regard adenocarcinoma as rare, occurring in only 6 per cent of cases.14 One of our cases of adenocarcinema was believed to have originated in the glands of Littre rather than the usual.site of origin in the prostatic utricle or Cowper glands, and is the subject of a previous report.17 Historically, management of deep urethral carcinoma was limited to observation, sounds, and cystostomy. l8 The first urethrectomy and inguinal node dissection was performed in 1893.18 Emasculation was introduced in 1895 and radiation therapy in 1925.f8 Younglg described a technique for the excision of a welllocalized, deep urethral carcinoma in 1939. McCrea and Furlong15 credited Zaslow and Priestly with resection of the posterior urethra and reconstruction using saphenous vein in 1947. ,Sullivan and GrabstaldzO stated, “. . . local recurrence with subsequent metastasis is the most frequently noted consequence following surgery,” suggesting inadequate surgical resection initially. To obviate this problem, and in an effort to deal surgically with more extensive tu-

530

TreatedRad. Surg. Other

pertinent

studies

(lF%)

4

0

9

T

(30%)

(3%)

are not included.38

mors, radical surgical procedures were introduced in the 1950s. Uhle and Holfelner in 195221 reported on the radical extirpation of an extensive urethral carcinoma. In 1953 Kaufman and Goodwin22 described a one-stage radical perineal excision for cancer of the urethra. In 1957 Marshall’ published a series of extensive deep urethral carcinomas managed successfully (80% j-year survival) with radical excision.’ While not duplicating the survival statistics, subsequent authors have reported favorable outcomes for cases managed with radical surgery (10-50 % j-year survival) .8.g,11 In 1969 Mackenzie and Whitmorez3 and Shuttleworth and Lloyd-Davies,‘O in separate communications, advocated an approach to deep urethral tumors even more radical than that initially proposed by Marshall. They described an anterior exenteration with a pubic arch excision. In 1982 Bracknerz4 published a description of a two-staged radical extirpative procedure, including a pubic arch excision. In 1983 Klein et d3 published a report on the successful management of Stage C disease with preoperative radiation therapy followed by inferior pubic rami resection with an en bloc radical excision. A report of a long-term survival of a patient with Stage C disease managed with radalone has recently been ical surgery published.25 Support for the radical surgical approach to deep urethral carcinoma has not been universal. In 1966 Mandler and Pool12 reporting on a nineteen-year experience at the Mayo Clinic,

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advocated a central role for radiation therapy. Subsequently, other authors have suggested that radical techniques be reserved for those lesions confined to the bulb without local extension.13 Despite the limitations applied to the use of radical surgery in the treatment of deep urethral carcinoma by some authors, a review of the literature supports the key role of radical surgery. Table II is a compilation of the major series published between 1957 and 1983, covering a total of 63 cases of deep urethral carcinoma. Thirty (47%) of the cases were managed with radical surgery. The five-year disease-free survival in this group of 30 cases was 9 (30 %). lg Of the 33 cases managed without radical surgery, there was a single fiveyear disease-free survivor. Several conclusions can be drawn from our data and the observations of others. Radical surgery has a definite role in the management of deep urethral carcinoma. It is most successful in patients with Stage B lesions, but survival from Stage C lesions has also been documented.3,25 Two long-term survivors of Stage D disease have been rep0rted.l Stage at presentation is the single most important prognosticator; outcome appears to be independent of grade or histology, or of duration of symptoms. We have had no case in which the pelvic nodes were histologically involved with tumor in the absence of inguinal nodal involvement. As others have observed, in view of a 100 per cent concordance between clinically palpable inguinal nodes and histologic involvement,s we recommend that inguinal and pelvic lymphadenectomy be done only when the inguinal nodes are palpable. Los

Angeles, California 90024 (DR. LUPU)

References 1. Marshall cinoma

VF: Radical of the male urethra,

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excision of locally extensive J Urol 78: 252 (1957).

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2. Bouldan JP, and Farah RN: Primary urethral neoplasms: review of 30 cases, ibid 125: 198 (1981). 3. Klein FA, et al: Inferior pubic rami resection with en bloc radical excision for invasive urethral carcinoma, Cancer 51: 1238 (1983). 4. Levine RL: Urethral cancer, Cancer 45: 1965 (1980). 5. Mostofi FK, and Edwards EB Jr: Tumors and tumor-like lesions of the male urethra, in Atlas of Tumor Pathology, Baltimore, Armed Forces Institute of Pathology, fast 8, 2nd series, 1973, p 263. 6. Riches EW, and Cullen TH: Carcinoma of the urethra, Br J Uro123: 209 (1951). 7. Flocks RH: The treatment of urethral tumors, J Uro175: 514 (1956). 8. Mullin EM, Anderson EE, and Paulson DF: Carcinoma of the male urethra, ibid 112: 610 (1974). 9. Ray B, Canto AR, and Whitmore WF Jr: Experience with primary carcinoma of the male urethra, ibid 117: 591 (1977). 10. Shuttleworth KED, and Lloyd-Davies RW: Radical resection for tumours involving the posterior urethra, Br J Urol41: 739 (1969). 11. King LR: Carcinoma of the urethra in male patients, J Urol 91: 555 (1964). 12. Mandler II. and Pool TL: Primarv carcinoma of the male urethra, ibid 96: 67 (1966). 13. Pointon RCS, and Poole-Wilson DS: Primary carcinoma of the urethra, Br J Urol40: 682 (1968). 14. Kaplan GW, Bulkey GJ, and Grayhack JT: Carcinoma of the male urethra, J Urol 98: 365 (1967). 15. McCrea LE, and Furlong JH Jr: Primary carcinoma of the male urethra, Urol Survey 1: 1 (1951). 16. Guinn GA. and Avala AG: Male urethral cancer: report of 15 cases including a’primary melanoma, J Urol 103: *176 (1970). 17. Sacks SA, et al: Urethral adenocarcinoma (possibly originating in the glands of Littre), ibid 113: 50 (1975). 18. Kreutzman HAR, and Colloff B: Primary carcinoma of the male urethra, Arch Surg 39: 513 (1939). 19. Young HH: A new radical oueration for carcinoma of the bulbous ure:hra, Surg Gynecol Obstet 68: 77 (1939). 20. Sullivan J, and Grabstald H: Management of carcinoma of the urethra, in Skinner DG, and deKernion J (Eds): Genitourinary Cancer, Philadelphia, W.B. Saunders, 1978, p 419. 21. Uhle CAW, and Holfelner ED: Treatment of carcinoma of the male urethra by radical surgical infrapubic removal, J Urol 68: 302 (1952). 22. Kaufman JJ, and Goodwin WE: Carcinoma of the male urethra: one stage surgical treatment by radical perineal excision and rectal transplantation of the divided trigone, Surg Gynecol Obstet 97: 627 (1953). 23. Mackenzie AR, and Whitmore WF Jr: Resection of pubic rami for tumor involving the posterior urethra, J Urol 100: 546 (1968). 24. Brackner BR: Exenterative surgery for posterior urethral cancer, Urology 19: 248 (1982). 25. Hopkins SC, Nag SK, and Soloway MS: Primary carcinoma of the male urethra, ibid 23: 128 (1984). 1

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