Squamous Cell Carcinoma of the Vulva Stage IA: Long-Term Results

Gynecologic Oncology 76, 24 –27 (2000) doi:10.1006/gyno.1999.5638, available online at http://www.idealibrary.com on

Squamous Cell Carcinoma of the Vulva Stage IA: Long-Term Results Javier F. Magrina,* ,1 Jesus Gonzalez-Bosquet,† Amy L. Weaver,‡ Thomas A. Gaffey,§ Kevin O. Leslie, ¶ Maurice J. Webb,\ and Karl C. Podratz\ *Department of Obstetrics and Gynecology and ¶Section of Pathology, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259; ‡Section of Biostatistics, §Division of Anatomic Pathology, and \Section of Gynecologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905; and †Hospital vall D’Hebron, Barcelona, Spain Received May 25, 1999

stage IA was defined accordingly to delineate a group of patients without risk of lymph node metastases, obviating the need for groin lymphadenectomy [5]. A retrospective review of our experience was undertaken to evaluate the risk of spread to lymph nodes and the long-term results with conservative and radical surgical therapy for patients with squamous cell vulvar cancer with a single T1 lesion with #1 mm of invasion.

Objective. The aim of this study was to evaluate the risk of metastases to lymph nodes and long-term results of radical and modified radical surgery in patients with a T1 squamous cell carcinoma of the vulva and <1 mm of invasion. Methods. A retrospective review of 40 patients with T1 squamous cell carcinoma of the vulva and <1 mm of invasion was performed. The clinical, pathologic, surgical, and follow-up data were abstracted from the patients’ records. All slides were reviewed by two pathologists according to previously established guidelines. The overall mean follow-up was 7.6 years. Results. Vulvar recurrence developed in 2 patients (5-year rate, 5.9%). There were no groin recurrences among 10 patients undergoing groin lymphadenectomy. One of the 30 patients (10year rate, 6.7%) without groin dissection developed groin metastases at 7.5 years, subsequent to an invasive vulvar recurrence. The 5- and 10-year cause-specific survivals were 100 and 94.7%, respectively. Conclusion. T1 squamous cell carcinoma of the vulva with <1 mm of invasion was associated with a low risk of vulvar recurrence and no groin node metastases. A low risk of subsequent groin node metastasis exists in patients developing an invasive vulvar recurrence. Long-term follow-up of these patients is recommended. Lesser forms of vulvar excision, such as wide local excision, were equally effective as radical vulvectomy for the prevention of vulvar recurrences. Patients treated by radical vulvar surgery experienced increased postoperative complications compared with patients treated by less radical surgery. © 2000 Academic Press Key Words: squamous cancer; stage IA; vulvar carcinoma.

MATERIAL AND METHODS A retrospective review of 238 patients with primary invasive squamous cell carcinoma of the vulva treated at the Mayo Clinic between January 1976 and December 1990 revealed 45 patients with lesions invading to a depth of 1 mm or less. The records of these patients were abstracted for age, medical conditions, clinical findings, tumor location and anatomic structures involved, operative treatment, pathologic findings, complications, recurrence, and survival. The pathology slides of all patients were reviewed retrospectively by a pathologist with regard to depth of invasion, tumor grade, lymphvascular permeation, lesion size, and number of lesions. The depth of invasion was measured with an ocular micrometer from the epidermal–stromal junction of the most superficial dermal papilla to the deepest point of tumor invasion. Tumor volume was calculated from three tumor dimensions in 19 patients. For 10 cases in which only two dimensions were available, the assumption was made that tumor volume did not exceed that of a sphere, with its diameter equal to the largest single dimension. Tumor volume was calculated from the three dimensions (D1, D2, D3) as V 5 3.1416/6 3 (D1 3 D2 3 D3). Invasion to .1 mm (4) or more than a single lesion (1) was noted in 5 patients who were omitted, leaving 40 patients for study. Radical vulvar surgery was considered a radical vulvectomy with bilateral groin lymphadenectomy through a single incision. Modified radical vulvar surgery included patients with vulvar excision, alone or with lymphadenectomy, unilateral or bilateral, through separate incisions.

INTRODUCTION Occasional reports have disclosed groin node metastases in patients with squamous cell vulvar cancer and #1 mm of invasion [1– 4]. However, when analysis was restricted to cases with a single T1 lesion and adhered to a set of specific rules for pathologic analysis, no groin node metastases were noted in 97 patients with invasion #1 mm [5]. Carcinoma of the vulva 1

To whom reprint requests should be addressed at Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259. 0090-8258/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

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SQUAMOUS CELL CARCINOMA OF THE VULVA STAGE IA

TABLE 1 Types of Vulvar Surgical Excision Type of surgery

Patients, No. (%)

Local excision Wide local excision Hemivulvectomy Simple vulvectomy Radical vulvectomy

4 (10) 9 (22.5) 3 (7.5) 7 (17.5) 17 (42.5)

TABLE 2 Early (within 42 Days) Postoperative Complications According to Type of Surgery Patients, No. (%) Modified radical

Complication site

RESULTS Pathologic slide review demonstrated invasion .1 mm in four patients initially identified as stage IA. One of these patients with 1.75 mm of invasion and with unilateral lymphadenectomy developed contralateral groin metastases 10.3 months after initial operation, and another with 1.3 mm of invasion and bilateral lymphadenectomy developed metastatic disease and died of the disease 8 years after initial operation. The third patient with 1.1 mm of invasion without lymphadenectomy experienced no recurrences at a follow-up of 6.3 years. A fourth patient had 2.2 mm of invasion. She underwent bilateral groin node dissection. She experienced a vulvar recurrence 3.4 years later and was free of disease 15.1 years after the initial operation. These patients were excluded from study. The fifth patient eliminated from the study had two lesions of 0.5 and 0.1 mm of invasion. This patient experienced three vulvar recurrences and subsequently developed metastases to groin, pelvic, and left supraclavicular nodes and died of her disease 9.4 years later. The mean age of the patients was 63.2 years (range, 34 –92 years). Previous malignancies were noted in 8 patients (20%). Four had had breast cancer, 2 cervical cancer, 1 colon cancer, and 1 basal cell cancer along with cervical cancer. Associated vulvar diseases were noted in 27 patients (67.5%), including 21 (52.5%) with vulvar intraepithelial neoplasia III, 1 (2.5%) with vulvar intraepithelial neoplasia II, 3 (7.5%) with hypertrophic vulvar dystrophy, and 2 (5.0%) with atrophic vulvar dystrophy. In decreasing order of frequency, presenting symptoms or signs were pruritus (52.5%), vulvar lesion (40.0%) or ulcer (20.0%), pain (15.0%), and bleeding (7.5%). None of the patients had palpable suspicious groin nodes. The surgical therapy for the vulva varied from local excision to radical vulvectomy (Table 1). Groin lymphadenectomy was performed in conjunction with several types of vulvar surgery in 10 patients (25.0%): unilateral in 2 and bilateral in 8. The mean size of the lesions was 1.2 cm (range, 0.1–2.0 cm). The mean tumor volume was 0.76 cm 3 (range, 0.0005– 4.19 cm 3). Forty lesions involved 54 anatomic sites. The labia majora were affected in 17 patients (42.5%) (right 8; left 8; both 1), the labia minora in 19 (47.5%) (right 12; left 5; both 2), the clitoral hood in 7 (17.5%), the perineum in 2 (5.0%), and the fourchette in 6 (15.0%).

Vulva Wound necrosis Cellulitis Wound hematoma Groin Wound necrosis

Radical (n 5 6)

With lymphadenectomy (n 5 4)

Without lymphadenectomy (n 5 30)

2 (33.3) 0 0

0 1 (25) 0

1 (3.3) 0 1 (3.3)

1 (16.7)

0

0

All lesions were squamous cell cancers. The grade (I–IV) of the tumor was distributed as follows: I, well differentiated, 20 patients (50.0%); II, moderately well differentiated, 15 patients (37.5%); and III, poorly differentiated, 5 patients (12.5%). There were no anaplastic lesions (grade IV). Lymphvascular permeation was not observed. Among the 10 patients undergoing unilateral or bilateral groin lymphadenectomy, none had positive nodes. The mean tumor volume of 27 patients in whom this measurement was available was 0.795 cm 3. The tumor volume for the 2 patients who experienced a recurrence was 0.157 and 0.524 cm 3. Postoperative early (within 42 days) vulvar and groin complications were noted in 6 patients (14.3%) and are detailed in Table 2 according to the type of surgery. Late complications (more than 42 days and until last follow-up) occurred in 7 (17.5%) patients and are summarized in Table 3 according to the type of surgery. TABLE 3 Late (More Than 42 Days and until Last Follow-Up) Complications Related or Probably Related to Surgery Patients, No. (%) Modified radical

Type of complication Any Lymphedema Cystocele Rectocele Stress urinary incontinence Uterine or vaginal prolapse

Radical (n 5 6)

With lymphadenectomy (n 5 4)

Without lymphadenectomy (n 5 30)

5 (83.3) 3 (50) 3 (50) 3 (50) 1 (16.7)

1 (25) 1 (25) 0 (0) 0 (0) 0 (0)

1 (3.3) NA 1 (3.3) 0 (0) 0 (0)

2 (33.3)

0 (0)

0 (0)

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MAGRINA ET AL.

TABLE 4 Clinical Features of Patients Experiencing Vulvar Recurrence and Groin Metastases Recurrence, years Patient

Lesion size, cm

Site

Depth, mm

Surgery

Vulva

Groin

1 2

131 2 3 1.5

RLM Left of clitoris

0.2 0.1

WLE RV

2.1 a 4.0 b —

— — 7.5 c

Status, years AW (6.1) DWD (7.7)

Note. AW, alive and well; DWD, dead with disease; RLM, right labia majora; RV, radical vulvectomy; WLE, wide local excision. a Right labia majora, WLE. b Right paraurethral, 2 3 1.1 cm, 3 mm of invasion, WLE. c Metastases to 4 of 9 right groin nodes, 2 of 13 right pelvic nodes, and 1 of 8 right aortic nodes.

The mean length of follow-up was 7.6 years (range, 0.1–16.3 years). Vulvar recurrences were observed in 2 patients (5-year rate, 5.9%) at 2.1 and 4.0 years after initial tumor resection (Table 4). There was 1 instance (5-year rate, 6.7%) of vulvar recurrence in the 17 patients treated by radical vulvectomy and 1 (5-year rate, 5.0%) among the 23 patients who had a lesser degree of vulvar excision (Table 1). There were no groin recurrences in the 10 patients who had a groin lymphadenectomy. Among the remaining 30 patients without lymphadenectomy, 1 (10-year rate, 6.7%) developed groin, pelvic, and aortic node metastases 7.5 years after initial operation and 3.5 years after experiencing a vulvar recurrence (Table 4). The primary lesion measured 2 3 1.5 cm, was moderately well differentiated, and was located to the left of the clitoris with only 0.1 mm of invasion. It was treated by local excision. She did well until 4 years later when she developed a right paraurethral, 2 3 1.1 cm, moderately welldifferentiated lesion with 3 mm of invasion. There were no palpable groin nodes. She underwent a wide local excision. She developed right groin metastases 3.5 years later and also had pelvic and aortic node metastases. She died of vulvar cancer 3 months later. Death was recorded in eight patients: one of vulvar cancer, at 7.7 years after initial operation, and seven of causes other than malignancy. The overall, cause-specific, and disease-free survivals at 5 years were 91.2, 100.0, and 94.1%, respectively. At 10 years, the overall, cause-specific, and disease-free survivals were 74.0, 94.7, and 94.1%, respectively. DISCUSSION Stage IA cancer of the vulva is a relatively common occurrence, being noted in 40 of 238 patients (16.8%) with squamous vulvar cancer evaluated for definitive therapy at the Mayo Clinic during a 15-year period. Our results are in agreement with previous recommendations for the treatment of patients with stage IA squamous cell carcinoma of the vulva [5]: wide local excision is adequate therapy. Although a rare patient may harbor subclinical groin

node metastases, routine groin lymphadenectomy is unwarranted. Strict adherence to the specific pathologic criteria for the diagnosis [5] of these lesions and the use of an ocular micrometer is essential because, on the retrospective slide review, four patients had .1 mm of invasion. Pathologic errors may result in the design of an improper operation. Vulvar recurrences were less common and occurred at an earlier date than in patients from our institution with stage I cancer. Vulvar recurrences occurred in 12% of 106 patients with stage I squamous cell carcinoma of the vulva [6] and in only 5% of patients in this series with stage IA. The mean time to recurrence for patients with stage I cancer was 6.4 years [6] and, for patients with stage IA cancer, 3.0 years. It is unknown whether late recurrences constitute a reactivation of subclinical disease after a long latency period or are a manifestation of new disease. No pathologic or clinical risk factors have been identified for vulvar recurrence in early carcinoma of the vulva after complete surgical resection [6, 7]. Tumor volume was not helpful as a prognostic factor, no differences being noted between the 2 patients who experienced a recurrence and the 27 patients without recurrence in whom this measurement was available. Although we had only two patients with vulvar recurrence, the radicality of the excision appeared not to influence their outcome. A similar recurrence rate was noted among patients with radical vulvectomy or modified radical vulvar surgery (5-year rates, 6.7 and 5.0%, respectively). The extent of surgical resection was likewise not influential in the outcome of patients with equal or more advanced stages of squamous cell vulvar carcinoma [8]. We observed no groin recurrences in 10 patients who underwent groin lymphadenectomy in conjunction with several types of vulvar excision and had histologically negative nodes. However, they have been noted, although rarely, in stage I vulvar cancer patients. We observed groin recurrence in 1 of 71 patients (1.4%) with stage I vulvar cancer and histologically negative nodes at initial operation [6]. Among the remaining 30 patients in this series without groin lymphadenectomy, 1 developed groin metastases. It is believed

SQUAMOUS CELL CARCINOMA OF THE VULVA STAGE IA

that all groin recurrences in undissected groins and in the absence of recurrent or new vulvar cancer are progression of untreated disease. Although groin metastases in undissected groins in general occur at an earlier date than vulvar recurrences, late metastases have been noted. We observed groin metastases in an undissected groin 10 years after excision of a T1 squamous vulvar lesion [6]. However, in this single instance, because the right groin metastases developed subsequent to an invasive right vulvar recurrence (or most likely a new primary tumor) and the primary lesion was on the left vulva and only 0.1 mm deep, we concluded that they are secondary to the recurrent invasive disease, not the primary microinvasive disease. It is estimated that half of the patients developing groin metastases in undissected groins might be cured if they had undergone a groin lymphadenectomy, because half of the patients with stage I superficially invasive carcinoma undergoing groin lymphadenectomy were found to have a single positive node [4]. Because the salvage rate for patients with groin recurrence is less than 10% [7], the avoidance of a groin lymphadenectomy in the presence of subclinical metastases results in a high likelihood of death for the patient. Early and late postoperative complications were higher in patients undergoing radical vulvar surgery than modified radical surgery. Similar findings were observed among patients with more advanced stages of vulvar cancer [8]. Early and late complications increased with the addition of groin lymphadenectomy to the vulvar excision and were highest in the radical surgery group. Vulvar intraepithelial neoplasia findings were noted in association with the microinvasive lesion in 55% of patients in this study. This has been observed in 60% of patients with squamous cell vulvar cancer [5]. Long-term follow-up of patients treated for vulvar intraepithelial neoplasia III has been recommended because 3.8% of patients treated for vulvar intraepithelial neoplasia III developed invasive carcinoma 7 to 18 years after therapy [9]. The criterion of a single vulvar lesion as a component of the

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definition of microinvasive carcinoma of the vulva [10] appears to have validity. The only patient with two lesions of 0.5 and 0.1 mm of invasion, not included in the study, died of her disease. Multicentric microinvasive disease may indicate a higher propensity for recurrence. Because the risk of lymph node metastases in patients with stage IA is nil, there is no role for intraoperative lymphatic mapping and sentinel node identification. REFERENCES 1. Hicks ML, Hempling RE, Piver MS: Vulvar carcinoma with 0.5 mm of invasion and associated inguinal lymph node metastasis. J Surg Oncol 54:271–273, 1993 2. Atamdede F, Hoogerland D: Regional lymph node recurrence following local excision for microinvasive vulvar carcinoma. Gynecol Oncol 34: 125–128, 1989 3. Homesley HD, Bundy BN, Sedlis A, Yordan E, Berek JS, Jahshan A, Mortel R: Prognostic factors for groin node metastasis in squamous cell carcinoma of the vulva. Gynecol Oncol 49:279 –283, 1993 4. Sedlis A, Homesley H, Bundy BN, Marshall R, Yordan E, Hacker N, Lee JH, Whitney C: Positive groin lymph nodes in superficial squamous cell vulvar cancer. A Gynecologic Oncology Group Study. Am J Obstet Gynecol 156:1159 –1164, 1987 5. Wilkinson EJ: Superficially invasive carcinoma of the vulva. Clin Obstet Gynecol 34:651– 661, 1991 6. Magrina JF, Webb MJ, Gaffey TA, Symmonds RE: Stage I squamous cell cancer of the vulva. Am J Obstet Gynecol 134:453– 459, 1979 7. Stehman FB, Bundy BN, Dvoretsky PM, Creasman WT: Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group. Obstet Gynecol 79:490 – 497, 1992 8. Magrina JF, Gonzalez-Bosquet J, Weaver AL, Gaffey TA, Webb MJ, Podratz KC, Cornella JL: Primary squamous cell cancer of the vulva: radical versus modified radical vulvar surgery. Gynecol Oncol 71:116 – 121, 1998 9. Jones RW, Rowan DM: Vulvar intraepithelial neoplasia III: a clinical study of the outcome in 113 cases with relation to the later development of invasive vulvar carcinoma. Obstet Gynecol 84:741–745, 1994 10. Microinvasive cancer of the vulva. Report of the ISSVD Task Force. J Reprod Med 29:454 – 456, 1984