CARCINOMA OF FEMALE URETHRA

Manitoba Experience: 1958-1987" P. HAHN, M.D. G. KREPART, M.D. K. MALAKER, M.D. From the Departments of Radiation Oneology and Obstetrics and Gynecology, The Manitoba Cancer Treatment and Research Foundation and University of Manitoba, Winnipeg, Manitoba, Canada

ABSTRACT--Fourteen female patients with primary urethral carcinoma were treated at thi Manitoba Cancer Foundation in the last twenty-nine years. The relationship of natural history ti the stage, location, and therapeutic modality has been reviewed. A higher stage and length 6 urethral involvement affected prognosis negatively, whereas lower stage had a positive prognost~ effect and location of tumor had no prognostic influence. Two patients with Stage C, who failed t receive inguinal node radiotherapy, died of disease recurring in the inguinal area. Patients wh received inguinal radiation (3 patients Stages B, C, and DI) had no regional recurrence. It is su gested that, for all femaIe urethral carcinoma, bilateral ilioinguinal nodes be included in the radi~ tion field. For radical treatment, iridium 192 insertion in combination with external beam treal ment is recommended.

Primary carcinoma of the female urethra is a rare malignaney and aeeounts for less than 0.02 percent of malignant disease oeeurring in women.1 A wide range of treatment modalities has been employed in this disease• Depending on the stage of disease, local resection, total urethreetomy, vulveetomy, external beam radiation, interstitial irradiation, anterior exenteration, or urinary diversion have been commonly used. Beeause of the rarity of this disease, there is no unanimous consensus regarding the therapeutie modality of choiee for various stages. For this reason, we have reviewed 14 patients with primary urethral cancer treated at the Manitoba Caneer Treatment and Research Foundation (MCTRF) between 1958 and 1987. Material and Methods From January 1958 to December 1987, 14 women with primary urethral eareinoma were *This work was supported by the Manitoba Cancer Treatment and Research Foundation.

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treated in our radiotherapy department. Oi ~ these 14 patmnts, 1 patmnt was treated for r~ current disease eighteen years after surgery. T~i diagnosis was eonfirmed histologieally in all p~ tients. Seven patients (50 % ) had squamous e~ eareinoma, 6 patients (43%) had transition cell carcinoma, and 1 patient (7 %) had adeni carcinoma. The tumors were staged aeeordii to the method of Grabstald and associate (Table I). •

,

Results

Clinical features Patients' ages at the time of treatment rat from thirty-five to seventy-four years (medii 64.5 years). The majority of patients were ovl sixty years orage (Fig. 1). One patient h a d situ carcinoma; none had Stage A disease, 2 Pi tients had Stage B, 5 patients had Stage C, a~ 6 had Stage D. Six patients (43 %) had urethri lesions located proximally, 5 patients (36 % ) h! distal lesions, and 4 patients (21%) had enti urethral involvement. Six patients had regior lymphatic metastasis at the time of diagnOS

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VOLUME XXXVII, NUMBI~

TA~L~;I.

Staging system of Grabstald and associates

t~ ~

Deseriotion

i?~ situ (limited to mucosa) { Submucosal(not beyond submucosa) ! B Muscular (periurethral muscle) { C eeriurethral C~ Infiltrating muscular wall of vagina C~ C~ plus invasion of vaginal mucosa Ca Infiltrating other adjacent structure such as bladder, labia, clitoris D Metastasis D~ Inguinal lymph node involvement D~ Pelvic lymph node involvement below aortic bifurcation Da Lymph node involvement above aortic bifurcation D4 D i s t a n t

8

1

1

1

7-q 7-1 [--q {:

30-39

i'

40-49

50-59

60-69

70-79

Age Rang~ Age distribution of patients with

1.

a.guinal lymph nodes were positive in 2 patents ' ~ on lymphangiogram, ~ and in i pat!ent this ia~ substantiated by biopsy. Three pat',em,ts had ~e!~ielymph node involvement on lymphangiogram, and in 2 of 3 patients metastases were ~io~ed by biopsy. One patient had a left scalene E :~de and Dara-aortie node involvement which ~!as confirmed by biopsy specimen from the e6k and para-aortie nodes.

!

Treatment ',, history, clinical stage, and results of of 14 patients are summarized in ix patients received external beam rame. External beam (32 MeV, ~°Co, 25 ation was delivered to the urethra ithout inclusion of pelvic or inguinal /

FEBRUARY 199i

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nodes. The aim was to deliver 4,500-6,000 eGy tumor dose over 4.5-6.5 weeks. One patient received only 3,300 eGy because she refused further radiotherapy and died later due to failure to control the disease. The remaining 5 patients received radiotherapy doses between 6,000-6,500 eGy. In 2 patients with Stage C disease, external radiation treatment was given to the primary sites only and did not include the inguinal nodes. The primary tumor responded well to radiotherapy and disappeared after 6,000 cGy, but inguinal node metastasis developed in both patients and they died. One patient with Stage D1 disease received external beam radiotherapy to the primary site and inguinal nodes and the tumor responded well to radiotherapy treatment; however pulmonary embolism developed four months later and the patient died. One patient with Stage Da disease received external beam radiation but died later with bone metastasis. One patient with Stage D1 disease received external beam radiation; she is alive and well without recurrence or distant metastasis. One patient who received preoperative radiotherapy plus radical vulveetomy, anterior exenteration is alive and well without tumor recurrence or distant metastasis. Three patients had external beam radiation plus local implant. One patient received 800 cGy external beam radiation plus gold 198 implant 5,900 eGy. Six years later local recurrence developed and the patient died with cancer. One patient with Stage C disease received 3,000 cGy of external beam radiation plus 1°Sir implant. Five years later bone metastasis developed but the patient is still alive with disease. One patient with Stage C disease received external beam radiation 5,000 cGy including inguinal nodes plus l°2Ir implant; this patient is alive and well without disease. Two patients had surgery and external beam radiation: 1 patient is alive without recurrence and the other patient died 2.5 years later with recurrence. One patient had cystourethreetomy and tantalum 182 insertion and died later of acute peritonitis. Early in the series, interstitial irradiation was given with la2Ta wires or ~°SAu implantation to maximum doses of 6,000 cGy to the urethra. In recent years we have been using 192Ir which has now replaced 198Au and ~S2Ta, because of their higher energy which poses a problem for radioprotection. ~92Ir insertion is done three to four days after external beam radiation treatment; 3,000-4,000 eGy is delivered. Radiotherapy is

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TABLE I1.

Stage of disease, treatment, and results

Treatment Year

Age

Histology

Stage

Location

1958 1960

71 49

TCC SCC

D2 C

Whole Proximal

1963

65

SCC

C2

Distal

1968 1969

63 63

SCC SCC

0 B

Distal Distal

1974

74

TCC

C

Whole

i974 1977 1977 1978 1979 1980

60 52 65 70 69 64

TCC Adeno. TCC SCC TCC SCC

C Da D1 D2 D2 B

Proximal Distal Proximal Distal Whole Whole

1984

35

SCC

C

Distal

1986

66

TCC

C2

Proximal

Treatment Ext. beam rad. 6,000 eGy Total eysteetomy, hyst., removal ant. vag. wall + ext. beam tad. 5,600 cGy Ext. beam rad. 800 cGy + QSAuimplant 5,900 eGy 182Ta 6,000 eGy Radical vulveetomy, inguinal lymphadenectomy 69, rec. 87 too. ext. beam rad. 5,600 eGy Cystourethrectomy + 182Ta implant 6,000 cGy Ext. beam rad. alone 6,500 cGy Ext. beam rad. 6,000 cGy Ext. beam rad. 6,500 cGy Ext. beam rad. 6,000 cGy Ext. beam rad. 3,300 cGy Ext., ext. beam rad. 3,000 eGy + 192Ir implant 3,000 cGy Ext. beam rad. 5,000 cGy + 192Ir implant 4,000 cGy Preop rad. 2,000 eGy + radical vulvectomy, ant. exenteration

Survival (Mos.) 4 35

Status DWD DWD:

70

DWD

33 221

DWD ANE~

7

DWD

12 18 119 48 73 95

DWDi DW~.i ANE~ DWDi! DWD ABM

35

ANE~

12

AN~

KEY: T C C = t r a n s i t i o n a l cell e a r e i n o m a ; S C C = s q u a m o u s eell e a r e i n o m a ; a d e n o . = a d e n o e a r e i n o m a ; ext. = e x t e r n a l ; t a d . r a d i a t i o n ; e G y = c e n t i g r a y ; h y s t . = h y s t e r e c t o m y ; a n t . = a n t e r i o r ; ree. = r e e u r r e n e e ; m o . = m o n t h s ; e x t . = excision; D W D = d i e d w i t h disease; A N E D = alive, n o etinieal e v i d e n e e of disease; A B M = alive w i t h b o n e m e t a s t a s i s .

relatively well tolerated. Complications from radiotherapy and interstitial irradiation were mild. A moderate degree of incontinence, frequeney, dysuria, transient diarrhea, mueositis, and postoperative radiation fibrosis (thickening of urethra) have been noted. One patient died of postoperative septicemia after laparotomy and exeisional biopsy of para-aortie lymph nodes. Comment The majority of our patients had locally advanced disease at the time of diagnosis and the outcome of treatment was poor. An attempt at early diagnosis should be made. This type of carcinoma appears to respond in the early stages and tends to become refraetory and lethal once a large tumor develops. 3 In our series, 3 patients had early stage eareinoma. One patient with Stage 0 received local implant because of ineomplete resection and did well without recurrence, but died of intereurrent disease six years later. One patient with Stage B carcinoma had surgery and external beam radiation and is still alive without disease. How108

ever, 1 patient with Stage B had external bean irradiation and 192Ir insertions is alive wii bone metastasis eight years after treatment. Fifty pereent of our patients had squamoui cell carcinoma, 43 percent transitional cell eari einoma, and 7 percent adenoeareinoma, bul there does not seem to be any eorrelation b4i tween histologic types of caneer and response t! radiotherapy in this limited series. Tumor loci tion does not appear to be related to the progni sis. Four patients had proximal location a: 4 patients had distal location. Involvement i the entire urethral length appears to be relat~ to the prognosis. In our series we had 4 patien with total urethra involvement: 2 of these p~ tients died within seven months, 1 patient di~i six years later with disease, and the other Pi tient is still alive with disease. The prognosis of female urethral earcinomi is related to the stage of disease. It is importaI to stage disease properly with lymphangiogra! or computerized tomography (CT) scans for at propriate management. In our series, 43 Pei~ cent had positive lymphangiogram; prognosis poor in these patients. All 4 of our patients wi :~

Seta~es D2 and Da carcinoma died of their dis~.A;;~lthough most of our patients had locally advanced disease, they responded well to external beam and interstitial radiation. In 2 patientS with Stage C disease, radiation treatment was given to the primary site only and the inguinal nodes were not included in the radiation field. In both patients inguinal metastasis subsequently developed and they died with disease. Itls important to cover the inguinal nodes even if tlaey are clinically staged as negative. One patient with Stage B, 1 with Stage D1, and 1 with S~age C carcinoma received external beam rai0therapy to the inguinal nodes; they are still ~e and well without evidence of recurrence. date, only 1 patient has been treated with a ~Nbination of preoperative radiotherapy fol6~ed by radical vulvectomy and anterior exen~e~ation. This patient is alive and well without relcurrence, but the follow-up time (12 months) istoo short to draw any conclusions. Both external beam and interstitial radiation ~r~ relatively well tolerated, and there were no se)i0us acute or,long-term side effects which affe~f the patient s quality of life. Even in locally ~ a n c e d disease, tumor responds well to radiotherapy. Interstitial implants are useful for delivering high doses to the tumor while sparing i~rrounding normal tissue. The combination of external beam and interstitial irradiation has a role in the management of patients with female urethral carcinoma. i Since the primary cancer of the female ~rethra is a rare malignancy which accounts for [ei~ than 0.02 percent of malignant disease occurring in women, it is difficult to do randdmized prospective clinical trials. We have

i

treated 14 patients with female urethral carcinoma during twenty-nine years at the Manitoba Cancer Foundation. The number of patients is small to draw any conclusions from this study; however it appears that Stage 0 should be treated with local excision. For incompletely excised Stage 0 disease, postoperative iridium insertion should be given to a dose of 6,000 cGy at 0.5 cm. Stage A should be treated with local excision followed by postoperative 19~Ir insertion for the entire urethral length. In the event of failure with local excision plus radiotherapy, anterior exenteration should be considered if the disease is still localized. In Stages B, C, D1, and D2 excision biopsy followed by external beam radiation treatment, 5,000 eGy should be applied to the primary site and whole pelvis for regional nodes and inguinal nodes. This should be followed by an iridium 192 insertion to 3,000 cGy in four to five days. Stages D3 and D4 prognosis is very poor; most likely this disease is incurable, however, 4,500-5,000 eGy external beam radiation to local tumor and pelvis may be palliative. 100 Olivia Street Winnipeg, Manitoba R3E OV9 Canada (DR. HAHN) ACKNOWLEDGMENT. To Carrie Campbell for secretarial assistance. References 1. Fagan GE, and Hertig AT: Carcinoma of the female urethra. Review of the literature, Obstet Gyneeol 6:1 (1955). 2. Grabstald H, Hilaris B, Hensehke U, and Whitmore WF Jr: Cancer of the female urethra, JAMA 197:835 (1966). 3. Bracken RB, et aI: Primary carcinoma of the female urethra, J Urol 116:I88 (1976).

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Carcinoma of female urethra. Manitoba experience: 1958-1987.

Fourteen female patients with primary urethral carcinoma were treated at the Manitoba Cancer Foundation in the last twenty-nine years. The relationshi...
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