Primary Carcinoma of the Female Urethra

Primary Carcinoma of the Female Urethra

\:'ol. 1 JC, Decemb~-r THE Cop) ,"ight © 19/:5 The V'./illiarns & Printed U.S.A. PRIMARY CARCINOMA OF THE FEMALE URETHRA SUVAS DESAI, JOHN A. LI...

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\:'ol. 1 JC, Decemb~-r

THE

Cop) ,"ight © 19/:5

The V'./illiarns &

Printed

U.S.A.

PRIMARY CARCINOMA OF THE FEMALE URETHRA SUVAS DESAI, JOHN A. LIBERTINO*

AND

LEONARD ZINMAN

From the Department of Urology, Lahey Clinic Foundation, New Eniland Deaconess Hospital and New Eniland Baptist Hospital, Boston, Massachusetts

Primary carcinoma of the urethra is uncommon. In a review of the literature in 1952 McCrea found 546 cases. 1 Herein we review our experience with primary carcinoma of the female urethra and evaluate the use of inguinal node dissection in this entity. Urethral carcinomas are classified as anterior (vulva-urethral) and posterior urethral tumors. Anterior tumors are confined to the distal third of the urethra but may involve the vestibule. Posterior tumors arise posteriorly and produce diffuse infiltration of the urethral wall. These tumors usually occur in elderly women. The majority of patients are more than 50 years old. The most frequently described symptoms are hematuria, frequency, dysuria, incontinence, urinary retention, tenesmus and pain. Diagnosis is made by biopsy of the tumor, which is seen on inspection, palpated externally or seen by panendoscopy. Squamous cell carcinoma is the most common type of urethral carcinoma. Adenocarcinoma, transitional cell carcinoma, the rare mesonephric carcinoma and mucoid carcinoma comprise the remainder. These tumors seem to arise from the epithelial lining of the urethra, usually at the junction of the transitional epithelium of the urethra and the stratified squamous epithelium of the vulva. Adenocarcinoma is said to arise from the periurethral glands of Skene. 2 Tumors involving the external meatal region metastasize to the superficial and deep inguinal lymph nodes. The more proximal tumors spread to the vesicosacral, hypogastric and external iliac nodes. Distant metastases occur late in the course of the disease and are infrequent on initial examination. 3 • 4 Treatment is variable. Local excision, alone or combined with irradiation, has been used for anterior carcinoma. Radical operations, in combination with irradiation, have been used for pasteAccepted for publication May 18, 1973. * Requests for reprints: Department of Urology, Lahey Clinic Foundation, 605 Commonwealth Ave., Boston, Massachusetts 02215. 1 McCrea, L. E.: Malignancy of the female urethra. Urol. Survey, 2: 85, 1952. 2 Rogers, R. E. and Burns, B.: Carcinoma of the female urethra. Obst. Gynec., 33: 54, 1969. 3 Staubitz, W. J., Carden, L. M., Oberkircher, 0. J., Lent, M. H. and Murphy, W. T.: Management of urethral carcinoma in the female. J. Urol., 73: 1045, 1955. 'Ruch, R. M., Frerichs, J. B. and Arneson, A. N.: Cancer of female urethra. Cancer, 5: 748, 1952.

rior carcinoma. Irradiation therapy alone has been administered for both types of tumor. In general, the reported results have not been good, especially in cases of posterior carcinoma. INCIDENCE AND TREATMENT

Between 1940 and 1970, 17 white women with primary carcinoma of the urethra were treated at our institution. The tumors were classified as anterior or posterior after the method described by Grabstald and associates. 5 The ages of the patients at the time of diagnosis varied from 40 to 85 years. Patients with suspicion of primary carcinoma arising in the bladder or vagina with secondary urethral involvement were excluded from study. One patient with primary carcinoma of the posterior urethra treated in late 1970 has been excluded from the statistical analysis. The most common presenting symptoms in our patients were bleeding, dysuria, urinary frequency and pain (table 1). Diagnosis was made in all cases by physical examination, cystopanendoscopy and biopsy. All patients were examined for inguinal node involvement. The modes of treatment were irradiation, alone or combined with radical operations, and local excision, alone or combined with irradiation. Irradiation consisted of either megavoltage radiotherapy or radium needle implants. RESULTS

Of the 16 patients, 10 had anterior and 6 had posterior carcinoma. There were no patients with coexistent urethral carcinoma and urethral caruncle. The tumor was fungating or cauliflower-like in 10 of the 16 patients (62.5 per cent). Biopsies were obtained in all patients. The type, location and relative frequency of the tumors are shown in table 2. Two grade 1, 7 grade 2, 4 grade 3, 1 grade 4 and 2 ungraded carcinomas were seen. At initial examination palpable inguinal nodes vvere present in 6 of the 16 patients (37 .5 per cent). Histopathology was obtained on all palpable lymph nodes. Of the 16 patients, 12.5 per cent had metastases to the inguinal nodes. Only 1 patient had evidence of metastases to the lungs and liver at initial examination. Treatment included irradiation as the primary method of therapy in 9 patients. Radium needle 5 Grabstald, H., Hilaris, B., Henschke, U. and Whitmore, W. F., Jr.: Cancer of the female urethra. J.A.M.A., 197: 835, 1966.

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DESAI, LIBERTINO AND ZINMAN

implants were used in nearly 50 per cent of this group. Five patients (31 per cent) were treated with local excision alone or combined with irradiation. Radical operations and irradiation were used in the remaining 2 patients (13 per cent). Inguinal lymph node dissection was performed in 3 patients (19 per cent). The over-all 5-year survival rate in our series was 5 of 16 patients (31 per cent): 40 per cent ( 4 of 10 patients) for anterior carcinoma compared to 17 per cent (1 of 6 patients) for posterior carcinoma. The 5-year survival rate with irradiation therapy was 37 .5 per cent (3 of 8 patients) and 40 per cent (4 of 10 patients) with local excision and irradiation. Results with posterior carcinoma have been poor. Only 17 per cent (1 of 6 patients) survived more than 5 years. This patient received radium needle implants with megavoltage irradiation and died with disease at 5 \4 years. Fifty per cent of the patients in this group (3 of 6) died of carcinomatosis in less than a year. Three patients with posterior carcinoma underwent radical operations. One had postoperative megavoltage irradiation and died 9 months postoperatively of recurrence. The second received preoperative x-ray therapy and is alive with disease at 2 ½ years. The third underwent anterior exenteration without preoperative or postoperative irradiation. She is free of disease 2 years postoperatively. DISCUSSION

The average age of our patients was 60 years, which was older than that described by McCrea 1 but similar to that reported by other investigators. 3 The most frequent symptoms were hematuria, frequency, dysuria and pain. The incidence of hematuria was 75 per cent in our patients compared to 63 per cent reported by Grabstald and associates.' The preponderance of epidermoid carcinoma has

TABLE

1. Symptomatolo{?y

Symptom

No.

% Frequency

Bleeding Dysuria Urinary frequency Pain Dyspareunia Urgency Mass Vaginal fistula

12 5 4 4 2 2

75 31 25 25 13 13 6 6

TABLE

2. Type and location of tumors

TABLE

Type

Anterior

Posterior

Total(%)

6 2

3 1 1

9 (56.2) 3(18.7) 2 (12.5) 2 (12.5)

No.(%)

Palpable nodes Biopsied nodes Metastatic nodes

6 (37.5) 6 (:17.5) 2 (12.5)

been described 2 • '· '· 6 by others and was found in 9 of our patients (56 per cent). Pointon and PooleWilson reported a 65 per cent incidence of squamous cell carcinoma. 7 The exact relationship between a urethral caruncle and urethral carcinoma remains unclear. Monaco and associates found an incidence of 10 caruncles in 63 patients ( 16 per cent) with urethral carcinoma. 6 We have not had a patient in whom a caruncle and carcinoma coexisted. Nevertheless it must be emphasized that a biopsy should be performed on all suspicious urethral lesions. The association between a urethral stricture and carcinoma has been stressed in men. However, this association is mentioned infrequently in women. One patient in our series had been treated elsewhere with periodic urethral dilatations for a year because of urethral stricture. No biopsy had been performed. This patient had an epidermoid carcinoma of the entire urethra on biopsy. Therefore, the index of suspicion should be high in patients with a history of resistant urethral stricture. The incidence of lymph node metastases is difficult to assess. Riches and Cullen quoted a 56 per cent incidence of inguinal node metastases and suggested that metastases in the inguinal glands is common and warrants full consideration of treatment either by removal or irradiation. 8 On the other hand, in 10 patients with enlarged inguinal nodes, Ruch and associates 4 found 2 with metastases and Taussig 9 found metastatic carcinoma in the inguinal nodes in 2 of 5 patients in whom the nodes were clinically enlarged. Monaco and associates reported a 22 per cent incidence of palpable inguinal nodes and 17 per cent of these individuals had metastatic carcinoma on histologic examination. 6 Staubitz and others reported a 47 per cent incidence of palpable inguinal nodes and 6 per cent had metastases. 3 In our series palpable inguinal nodes were present in 37.5 per cent (6 of 16) of the patients (table 3). All patients with palpable nodes had inguinal node bi0psies. Only 12.5 per cent (2 of 16 patients) had metastatic carcinoma in the groin. The remainder had inflammatory inguinal adenopathy. 6 Monaco, A. P., Murphy, G. B. and Dowling, W.: Pnmary cancer of the female urethra. Cancer 11: 1215

1958.

,

'

Pointon, R C. S. and Poole-Wilson, D. S.: Primary carcmoma of the urethra. Brit. J. Urol., 40: 682 1968 8 Riches, E. W. and Cullen, T. H.: Carcino~a of the urethra. Brit. J. Urol., 23: 209, 1951. 'Taussig, F. J.: Pri_mary cancer of the vulva, vagina and female urethra: five year results. Surg., Gynec. & Obst., 60: 477, 1935. 7

Epidermoid Adenocarcinoma Transitional Undifferentiated

3. Inguinal node involvement: 16 patients

Nodal Involvement

695 Therefore, we think that palpable inguinal nodes do not necessarily indicate metastases. The value of prophylactic inguinal node dissection has not been clearly established and wound problems after inguinal node dissection are significant. It would thus seem logical to perform a preliminary biopsy in all patients with palpable inguinal nodes. Inguinal node dissection could be decided upon after the results of the node biopsy are available. Our over-all 5-year survival rate of 31 per cent (5 of 16 patients) is similar to that reported by other investigators. 2 · 3 • 6 Rogers and Burns 2 had a 5year survival rate of 29 per cent and Staubitz and associates' had a rate of 28 per cent. As anticipated, survival was better with anterior carcinoma than with posterior carcinoma. Our 5-year survival rate was 40 per cent (4 of 10 patients) with anterior carcinoma and 17 per cent (1 of 6 patients) with posterior carcinoma. Monaco and associates 6 had a 30 per cent 5-year survival rate with anterior carcinoma and none with posterior, while Rogers and Burns 2 had a 5-year survival rate of 29 per cent with anterior carcinoma and none with posterior. Grabstald and associates had only one 5-year survivor in 38 patients with epidermoid carcinoma involving the posterior urethra. 5 In our series the over-all 5-year survival rate with irradiation therapy was 37.5 per cent (3 of 8 patients). Two-thirds of these patients had radium needle implants as the primary mode of treatment. The 5-year survival rate with local excision alone or combined with irradiation was 40 per cent in anterior carcinomas (4 of 10 patients). It seems that the best results were obtained with local excision and interstitial irradiation in the form of radium needle implants in patients with anterior carcinoma and negative inguinal nodes. In addition, the increased survival rates perhaps reflect the better over-all prognosis of anterior carcinoma. Reviewing the results with radical operations, Grabstald and associates reported one 5-year survivor in 38 patients.' Monaco and associates discussed 2 anterior exenterations in 23 patients. 6 One patient died of metastatic carcinoma in 10 months and the other was alive with melanotic sarcoma of the urethra at 1 ½ years. Riches and Cullen conclude that a radical operation is applicable in a minority of patients, with a good prospect of survival in these patients. 8 Three patients were treated with a radical operation at our institution. Of these patients 2 had a radical operation com-

bined with irradiation. One died of carcinomatosis at 9 months while the other one is alive with disease at 2 years. The third patient, not included in the statistical analysis, had an anterior exenteration without radiotherapy. She is free of disease at 2 years. All of these patients had carcinoma of the posterior urethra. Our results with radical operations have been disappointing. We do not perform prophylactic inguinal node dissections. If the patient has evidence of nodal disease we would perform a node dissection unless the nodal disease is massive or fungating. We believe, as do other investigators, that the prospects of radical operations combined with irradiation must be explored, especially in younger patients. 2 • 3 • 5 • 6 • 8 Patients who have high grade tumors with nodal involvement will not do as well as those who have low grade tumors with nodal involvement. Again, no treatment has been accepted as standard. Therefore, individualization of treatment becomes important. Factors to be considered include age, location, type, grade, duration, inguinal node involvement, stage and general condition of the patient. CONCLUSION

Seventeen cases of primary carcinoma of the urethra have been presented. The association of a urethral caruncle with urethral carcinoma has been discussed. The importance of biopsy for resistant strictures or doubtful lesions of the female urethra is emphasized. The importance of inguinal node biopsy, the incidence of nodal metastasis and the indications as well as the complications of inguinal node dissection are discussed. Local excision with radium needle implants should be the primary mode of treatment for anterior carcinoma. 1 • 3 ' '· 10 Results with posterior carcinoma have been uniformly poor with all forms of therapy. The potentials of radical operations with irradiation therapy need to be explored further, The over-all 5-year survival rate was 31 per cent (5 of 16 patients) in our series; 40 per cent (4 10 patients) with anterior carcinoma and 17 per cent (1 of 6 patients) with posterior tumors. The importance of individualization of treatment is emphasized.

of

10 Steyn, J., Hall, lVL and Logie, N. J.: Adenocarcinoma of the female urethra. Brit. J. UroL, 39:504, 1967.