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Squamous cell carcinoma of the vulva: Staging and surgical treatment

Squamous cell carcinoma of the vulva: Staging and surgical treatment
Literature review current through: Jan 2024.
This topic last updated: Jan 25, 2024.

INTRODUCTION — Vulvar cancer is the fourth most common gynecologic cancer in high-resource countries and comprises approximately 5 to 6 percent of malignancies of the female genital tract. Although various histologic subtypes of vulvar cancer exist, the vast majority are squamous cell carcinoma (SCC). (See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment", section on 'Epidemiology'.)

This topic discusses the staging, treatment, and prognosis of patients with vulvar SCC. The clinical presentation, diagnosis, and pathology of vulvar cancer; medical therapy; the techniques for radical vulvectomy; and the management of other histologies are reviewed separately.

(See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment".)

(See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis".)

(See "Radical vulvectomy".)

(See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment", section on 'Treatment'.)

VULVAR ANATOMY — The vulva is part of the female external genitalia, which includes the labia majora, labia minora, clitoris, vestibule, vaginal introitus, and urethral meatus (figure 1). The Bartholin complexes (vestibular glands and ducts) are also considered components of the vulva, and malignancies arising in these structures are grouped with vulvar cancers. (See "Surgical female urogenital anatomy", section on 'Vulva (external female genitalia)'.)

Functionally, the vulva directs urine flow, prevents foreign bodies from entering the urogenital tract, and is a sensory organ for sexual arousal. The blood supply to the vulva is predominantly from the internal pudendal artery with a smaller contribution from the external pudendal artery. The anterior aspect of the vulva is innervated by the ilioinguinal and genitofemoral nerve. The posterior aspect of the vulva is innervated by the perineal branch of the posterior cutaneous nerve of the thigh laterally and the pudendal nerve centrally. The majority of the vulva is drained by lymphatics that pass laterally to the superficial inguinal lymph nodes. The clitoris and anterior labia minora may also drain directly to the deep inguinal or external iliac lymph nodes.

MODE OF SPREAD — Vulvar carcinoma metastasizes by a variety of mechanisms. Understanding these potential pathways is important for the evaluation and treatment of these tumors. Modes of spread include:

Direct extension to adjacent structures (eg, vagina, urethra, clitoris, anus).

Lymphatic spread to regional lymph nodes can occur early in the course of disease, even in patients with small lesions. Vulvar cancer most commonly spreads initially to the superficial inguinal nodes immediately lateral to the pubic tubercles, which is why these nodes are sampled as part of staging. Lesions that are on one side of the vulva generally spread only to the ipsilateral inguinofemoral nodes (also referred to as groin nodes).

In one report, approximately 10 percent of superficially invasive vulvar cancers (ie, lesions with >1 but <3 mm depth of stromal invasion) had lymph node metastases at diagnosis [1]. In other reports, lymphovascular space invasion, tumor stage, grade, and depth of infiltration were the variables with the strongest association with lymph node metastasis [2,3].

Formal evaluation on the distribution of sentinel lymph nodes in patients with vulvar cancer shows that 100 percent of sentinel nodes lie over or medial to the femoral vessels. In one study that included over 59 patients with a vulvar cancer <4 cm [4], the sentinel nodes were superficial in approximately 85 percent of cases, and in 15 percent, the sentinel nodes laid deep to the cribriform fascia. These observations have important implications for the extent of inguinofemoral lymphadenectomy as well as the selection of radiotherapeutic target volumes and techniques.

Hematogenous dissemination, which typically occurs late in the course of the disease, is rare in patients without inguinofemoral lymph node involvement. In one series, patients with fewer than three positive lymph nodes at the time of initial diagnosis had a significantly lower risk of hematogenous spread as compared with those with three or more positive lymph nodes (4 versus 66 percent, respectively) [5].

PRETREATMENT EVALUATION — Before proceeding with staging and surgical and/or adjuvant therapy for vulvar cancer, the patient should undergo evaluation for ability to tolerate treatment and for conditions associated with vulvar cancer.

Issues specific to the preoperative evaluation of patients with vulvar cancer are discussed here. General principles of the preoperative evaluation of patients for gynecologic surgery are discussed separately. (See "Overview of preoperative evaluation and preparation for gynecologic surgery".)

Ability to tolerate treatment — The patient should be evaluated for the ability to tolerate surgery and adjuvant therapy. A complete history and physical examination and appropriate laboratory testing are performed [6]. (See "Overview of preoperative evaluation and preparation for gynecologic surgery".)

Vulvar cancer typically occurs in older patients. Management of medically frail patients is discussed separately. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Patients who are medically frail'.)

Other HPV-associated diseases — A common etiology of vulvar cancer is human papillomavirus (HPV) infection [7]. Thus, the pretreatment evaluation should include evaluation for other HPV-associated disease (eg, cervical or vaginal intraepithelial neoplasia) and, if present, whether it requires surgical management or surveillance. (See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment", section on 'Risk factors and etiology'.)

We perform vulvar colposcopy in all patients because squamous intraepithelial lesions are often multifocal. In addition, we perform cervical cytology and colposcopy of the cervix and vagina. (See "Colposcopy".)

STAGING AND SURGICAL TREATMENT — The staging system for vulvar cancer is a hybrid of a clinical and surgical staging approach. Surgical assessment and treatment techniques for both vulvar excision and lymphadenectomy have evolved to allow less extensive surgery, while providing effective diagnosis and treatment.

Staging system — In vulvar cancer staging, tumor size, depth of invasion, and local extension are determined mostly on physical examination and vulvar biopsy, and lymph nodes are evaluated by physical examination, imaging, and lymphadenectomy or sentinel lymph node biopsy (SLNB).

The 2021 International Federation of Gynecology and Obstetrics (FIGO) staging system is shown in the table (table 1) [8]. The American Joint Committee on Cancer (AJCC) publishes the TNM (tumor-node-metastasis) pathology notation that correlates with the FIGO stages [9]. The current TNM notation is based on the older (2009) FIGO version, and will not be presented here until it has been updated.

Previous systems for vulvar cancer staging were clinical systems. The shift was made from solely clinical staging because clinical staging may miss patients with microscopic nodal metastases [10,11]. Thus, the combined system was implemented because lymph node metastases are the most important prognostic factor for vulvar cancer [12-15].

Vulvar melanoma is staged according to the melanoma staging system and discussed separately. (See "Tumor, node, metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma", section on 'Eighth edition AJCC TNM staging'.)

Clinical staging

Physical examination — The physical examination includes assessment for tumor diameter, local extension (to vagina, urethra, anus, bladder, rectum), and enlarged inguinofemoral lymph nodes, and includes:

A complete pelvic examination is performed.

The vulva is inspected and the diameter of the primary tumor(s) measured. To help guide surgical approach, the proximity of lesions to functionally important midline structures (clitoris, vagina, urethra, and anus) is measured and recorded.

To assess for local extension of invasive disease:

The perineum, anus, vagina, and urethra are inspected for lesions suspicious for local extension of invasive disease. Vulvar cancer is often multicentric.

Bimanual pelvic examination and rectovaginal examination are performed to assess local extension to the vagina, anus, rectum, or bladder (table 1).

Colposcopy is performed of the vulva, vagina, and cervix.

Biopsies are performed as needed to confirm invasive disease and assess depth of invasion.

The inguinal and supraclavicular lymph nodes are palpated [16]. If the inguinofemoral nodes are enlarged, a biopsy is performed to confirm nodal metastases. This may be performed as a fine needle aspiration in the office or at the time of surgery. The presence of clinically palpable inguinofemoral nodes is an important determinant of the approach to further lymph node evaluation and management. Palpable supraclavicular nodes should be evaluated with imaging, since this may be evidence of distant metastases. (See 'Inguinofemoral lymph nodes' below.)

For patients with locally advanced primary lesions, an examination under anesthesia may be necessary to allow for a thorough evaluation to determine the extent of disease. Cystoscopy and proctoscopy may be performed at this time, if clinically indicated.

For patients whose initial treatment will not be surgery because of either frailty or the extent of the primary tumor, it is helpful to take photographs of the extent of visible disease and enter these into the medical record. This assists in treatment planning and modification of treatment. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Patients who are medically frail' and "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Unresectable, locally advanced disease'.)

Imaging studies — Diagnostic imaging of the pelvis, abdomen, or chest may complement physical examination, depending upon the findings on physical examination.

Pelvic/abdominal imaging may be performed to assess:

Tumor size

Extent of local extension to surrounding structures (anus, rectum, urethra, bladder)

Pelvic lymph node metastases

Liver or lung metastases

In our practice, we perform pelvic/abdominal imaging in patients with the following characteristics:

Symptoms that suggest metastases (ie, bowel and bladder dysfunction) [10].

Tumors ≥4 cm in diameter – For smaller tumors, preoperative imaging is generally not performed, as it does not change the surgical management. For patients with smaller tumors and who are surgical candidates, we perform imaging if there is node-positive disease on SLNB.

Clinically palpable inguinofemoral nodes

Not candidates for primary surgical therapy based on cancer extent or medical comorbidities

There are few data comparing imaging modalities in vulvar malignancies, and the choice of imaging modality to evaluate locoregional and distal spread is often based on institutional or personal preference:

Magnetic resonance imaging (MRI) of the pelvis may assist in defining the local extent of disease if surgery is planned, especially for patients with locally advanced cancers. An MRI is also helpful in radiation planning in patients who are not surgical candidates. The accuracy of contrast-enhanced MRI in determining the size of the lesion in one study was 83 percent, and for detecting groin lymph node metastases was 85 percent [17].

The use of positron emission tomography (PET) and PET/computed tomography (CT) in gynecologic malignancies has been increasing. However, prospective data on the utility of PET/CT for identifying groin metastases are limited. One small prospective study demonstrated a sensitivity of 80 percent and specificity of 90 percent in detecting nodal metastases [18].

In a prospective study comparing PET and PET/CT with contrast-enhanced MRI or CT, the sensitivity and specificity of PET compared with CT/MRI for detecting lymph node metastases were similar (92 and 91 versus 92 and 100 percent). PET had a significantly higher false-positive rate than CT/MRI in detecting pelvic or distant metastases [19].

In our practice, we use PET/CT (which includes imaging of the abdomen, pelvis, and chest) to evaluate for locoregional and distant metastases due to the ability to combine it with a diagnostic CT scan as needed.

A chest radiograph is obtained if lung metastases are suspected based on a symptom of shortness of breath and if no other chest imaging has been performed.

Vulvar excision — Vulvar excision of the lesion(s) is performed, if feasible. The choice of location, depth, and width of excision are determined by the incision required to remove invasive disease with a reasonable margin, while at the same time limiting morbidity and disfigurement.

As an overview, the surgical approach chosen depends upon the size and extent of the lesion (table 2) [20] (see "Vulvar wide local excision and simple vulvectomy" and "Radical vulvectomy"):

Tumor confined to vulva (ie, no extension to adjacent perineal structures) – Radical local excision. This is sometimes referred to as "wide local excision," but the most important issue is the depth of the resection, not the width. In order to be certain about the true depth of invasion, one needs to resect the tissue deep enough to the surface so that you can actually measure the depth accurately [6,21].

Tumor of any size with extension to adjacent perineal structures (ie, urethra, vagina, anus) – Modified radical vulvectomy (eg, modified radical hemivulvectomy, modified radical anterior vulvectomy, modified radical posterior vulvectomy).

Extension to any of the following: upper/proximal two-thirds of urethra, upper/proximal two-thirds vagina, bladder mucosa, rectal mucosa, or fixed to pelvic bone – Most of these patients are treated with definitive chemoradiation. After chemoradiation, many lesions respond completely or there is only a small amount of residual disease. In cases where there is residual tumor, surgery may then be performed to resect the primary site to ensure complete response. Exenteration is an option with colostomy or urethral diversion in selected patients for whom chemoradiation therapy is unsuccessful. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Unresectable, locally advanced disease' and "Exenteration for gynecologic cancer".)

Historically, all patients with vulvar cancer were staged and treated with en bloc radical vulvectomy and bilateral inguinofemoral lymphadenectomy through a butterfly incision, a procedure associated with high rates of survival, but also significant morbidity, including poor wound healing, lymphedema, and adverse effects on body image and sexual function [22-27].

In current practice, radical local excision (also known as a radical partial vulvectomy, radical hemivulvectomy, or modified radical vulvectomy) is typically used. The efficacy of this procedure is comparable with more extensive procedures, and it results in less morbidity and disfigurement than en bloc radical vulvectomy (figure 2) [28]. (See "Vulvar wide local excision and simple vulvectomy".)

There are no prospective data comparing radical local excision with radical vulvectomy. A meta-analysis including two small observational studies (n = 94) that addressed this issue found no difference in the incidence of local recurrence between the two procedures [29]. A slightly larger retrospective study (n = 122) reported no differences in the disease-free survival rate at five years for those treated by radical excision or radical vulvectomy (98 versus 93 percent, respectively) [30].

The depth of the dissection for radical local excision is the same as in modified radical or radical vulvectomy (from the skin to the urogenital diaphragm) [31].

A tumor-free margin ≥1 cm is required since a smaller margin is associated with an increased local recurrence risk [6,21,32-35]. This was shown in a retrospective series of 135 patients that found a lower rate of local recurrence in cases with a normal tissue margin of ≥1 cm compared with <8 mm (0 versus 50 percent) [21]. Shrinkage of normal tissue margins consequent to fixation for histopathologic sectioning has been estimated to be 20 percent [36-38]. Therefore, an 8 mm margin in fixed tissue will correspond to an approximate clinical margin of 1.0 cm in vivo.

When presurgical clinical examination reveals tumor extension within <1.0 cm from structures that will not be surgically removed (eg, urethra, clitoris, anus), the potential of an inadequate surgical margin on final examination should be anticipated. For such patients, preoperative or definitive chemoradiation may be of benefit. (See 'Treatment of positive or narrow margins' below.)

In our practice, we use a technique for radical local excision that utilizes two or three separate incisions (figure 3). The first incision is made to perform a radical local excision. This involves resection of the primary tumor with a width of 1 cm clinical margins laterally and, in terms of depth, a dissection down to the perineal membrane (also known as the deep fascia) of the urogenital diaphragm. The excision can be unilateral in most cases. Additional (and separate) incisions are for the inguinofemoral lymphadenectomy, which may be unilateral or bilateral depending on the primary vulvar tumor. This allows for an intervening skin bridge to remain intact, which helps to conserve vulvar anatomy and aid wound healing [39]. Of note, a cancer recurrence in the skin bridges can occur and is attributed to in-transit contamination of dermal lymphatics. This is uncommon and rarely seen unless there is extensive metastatic spread to regional lymph nodes or lesions >4 cm [29].

Treatment of positive or narrow margins — For patients with tumor at or close to the surgical margins (≤8 mm) identified at final pathologic analysis, we suggest re-excision when feasible to ensure complete resection. For those patients who do not want or cannot undergo repeat surgery, limited data suggest that RT is a reasonable alternative, especially when further surgery could compromise the function of adjacent midline structures (clitoris, vagina, anus) [36,40,41]. Vulvar radiation can be associated with significant skin toxicity, and so these cases need to be individualized.

The National Comprehensive Cancer Network (NCCN) guidelines regarding vulvar cancer advise that other factors, such as nodal status, should be considered in deciding whether to perform a re-excision in patients with positive or narrow margins [6]. Repeat surgery may not be beneficial in patients with inguinal metastases that require chemotherapy and/or radiation. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Chemoradiation versus RT alone'.)

Although our cutoff for further intervention is ≤8 mm, studies are evaluating whether intervention is necessary in all such cases. In a retrospective pathology slide review of 287 patients, the risk of local recurrence was 43 percent and, on multivariate analysis, was unaffected by margin distances of 8, 5, or 3 mm, but was influenced by the presence of premalignant lesions at the margin (differentiated vulvar intraepithelial neoplasia) [42]. In a separate retrospective study including 37 patients with stage I disease and close margins, there was no statistically significant difference in the risk of local recurrence or death between patients who underwent additional treatment (re-excision or RT) and those who did not [43]. Given that these studies are small and retrospective, more data are needed.

Coexistent precancerous lesions or dermatoses — Vulvar cancer may coexist with vulvar or vaginal intraepithelial neoplasia or dermatoses (eg, lichen sclerosus). At the time of surgical treatment or staging, intraepithelial neoplasia should be excised, but it is not necessary to excise benign lesions. Because vulvar cancer may be a manifestation of "field cancerization," lifetime observation of residual vulvar tissue is typically required when conservative treatment approaches are employed.

Inguinofemoral lymph nodes — Assessment for inguinofemoral lymph node metastases is essential for staging. The approach to evaluation is guided by whether the inguinofemoral nodes are palpable on examination. Selected patients with stage IB or II disease are candidates for SLNB. The surgical procedure for evaluation or debulking of inguinofemoral nodes is performed concomitant with excision of the vulvar tumor.

As an overview, the approach to inguinofemoral nodes is:

For patients with no palpable nodes on groin examination, lymphadenectomy is performed for most patients:

For stage IA (table 1), no lymphadenectomy is performed. Lymph node metastases are rare in this group (<1 percent) [34].

For stage IB or higher, inguinofemoral lymphadenectomy is performed. In this group, the risk of inguinofemoral lymph node metastases is ≥8 percent [44].

Some patients with stage IB or II disease are candidates for SLNB rather than complete lymphadenectomy. (See 'Sentinel lymph node biopsy' below.)

While lymph node evaluation is recommended for patients with stage IB or higher, rates of utilization indicate that disparities in access to care continue to exist. In a retrospective study including over 5600 patients with stage IB or higher disease in the United States, lymph node evaluation with either lymphadenectomy or SLNB was performed in only 66 percent of patients [45]. Patients ≥80 years, Black race, and those treated at low-volume or nonacademic hospitals were less likely to undergo lymph node evaluation.

For patients with palpable inguinofemoral nodes, lymph node biopsy is performed. This may be done as an office procedure with fine needle aspiration or in the operating room as a frozen section. If lymph node involvement is confirmed, patients are typically treated with definitive chemoradiation rather than debulking or lymphadenectomy. The rationale for this approach is that these patients will still require radiation or chemoradiation of the inguinofemoral nodes and upfront nodal surgery may delay or increase morbidity of (chemo)radiation.

No palpable groin nodes on examination — Inguinofemoral lymphadenectomy or SLNB is performed in all patients with stage IB or higher disease who have a clinically negative lymph node examination.

Inguinofemoral lymphadenectomy — An inguinofemoral lymphadenectomy consists of removal of the inguinal (superficial) and femoral (deep) lymph nodes (figure 4 and figure 5).

In terms of surgical technique, most gynecologic oncologists perform radical local excision or modified radical vulvectomy with inguinofemoral lymphadenectomy through separate groin incisions for presumptive stages I to II disease (figure 6). (See 'Vulvar excision' above.)

A classical inguinofemoral dissection requires removal of both superficial and deep inguinal lymph nodes. The deep nodes are situated within the fossa ovalis, and the superficial lymph nodes surround the greater saphenous vein and superficial epigastric vessels [40].

Superficial lymphadenectomy alone had been studied, but does not appear to be effective for vulvar cancer [29,37]. This approach entails removal of the inguinal lymph nodes without the use of a deep excision to retrieve femoral nodes. As an example, the prospective Gynecologic Oncology Group (GOG) 74 trial found that patients with stage I disease who underwent an ipsilateral superficial lymphadenectomy and radical local excision had a significantly higher risk of pelvic recurrence (in the groin and/or vulva) compared with historic controls who were treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy (15.6 versus 6.7 percent, respectively) [37]. Of note, groin recurrences were only seen in those patients treated with an ipsilateral lymphadenectomy (nine cases, 7.4 percent). This may be explained by the observation that the first sentinel lymph node may lie below the cribriform fascia in approximately 15 percent of patients [4].

Unilateral versus bilateral — Unilateral rather than bilateral lymphadenectomy is performed whenever possible because a unilateral procedure decreases postoperative morbidity.

Multiple observational studies of patients with early-stage, lateral disease found that unilateral lymphadenectomy was associated with a <3 percent risk of contralateral groin node metastases [10,37,46].

Unilateral inguinofemoral lymphadenectomy has a potential benefit of a reduction in morbidity. Bilateral inguinofemoral lymphadenectomy is associated with a high morbidity rate, including a 20 to 40 percent risk of wound complications and a 30 to 70 percent risk of lower extremity lymphedema [37,40,47,48]. There are no studies that have directly compared unilateral with bilateral procedures regarding morbidity; however, this is likely to reduce the incidence of wound infections, and lymphedema is limited to the ipsilateral lower extremity.

A retrospective study of 122 patients with lateral T1 and T2 squamous cell carcinomas of the vulva showed that the rates of lymphedema, lymphocyst formation, and wound separation were significantly lower among patients undergoing unilateral versus bilateral inguinal lymphadenectomy (7.5, 7.5, and 3.2 percent versus 26, 23, and 6.7 percent, respectively) [30]. The average length of stay for patients undergoing radical hemivulvectomy with ipsilateral inguinal lymphadenectomy was also shorter than for patients undergoing radical vulvectomy and bilateral inguinal lymphadenectomy (5.0 versus 9.6 days, respectively).

We suggest unilateral lymphadenectomy for patients with vulvar squamous cell carcinoma who meet the following criteria [6]:

Primary lesion <2 cm in diameter

Lateral lesion (≥2 cm from the vulvar midline)

No palpable inguinofemoral nodes on examination

When unilateral lymphadenectomy is performed, the nodes should be sent for intraoperative frozen pathology evaluation. If metastases to the inguinofemoral nodes are found at the time of surgery or at final pathology, contralateral lymphadenectomy should be performed. If further surgery may compromise the function of adjacent midline structures (clitoris, vagina, and anus) or the patient refuses further surgery for any reason, we would offer the patient adjuvant RT. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Chemoradiation versus RT alone'.)

Patients who will receive RT — It is important to note that lymph node assessment is performed even if radiation therapy (RT) is planned. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Node-negative disease'.)

This was evaluated in a 2011 systematic review that concluded that while primary RT was associated with less toxicity compared with inguinofemoral lymphadenectomy, including a lower incidence of lymphedema and life-threatening cardiovascular complications, it was associated with a higher recurrence rate and lower disease-specific survival [49]. However, this analysis was limited by the inclusion of only one randomized trial of 52 patients [50], which was the only paper to fulfill selection criteria prespecified in the methodology. In addition, although patients in this trial were prospectively enrolled and randomized to treatment, the technical administration of RT to a prescription depth in tissue of only 3 cm in the inguinofemoral regions represented therapeutic underdosing or a "marginal miss" in many patients. In patients with micrometastatic disease (≤2 mm), radiation alone without lymphadenectomy is appropriate [51].

Sentinel lymph node biopsy — Sentinel lymph node biopsy (SLNB) is an alternative to inguinofemoral lymphadenectomy for selected patients with stage I or II disease (table 1) and no palpable inguinofemoral nodes. SLNB appears to be effective in detecting inguinofemoral lymph node metastases without increasing the risk of groin recurrence and helps to avoid the acute and late morbidities associated with complete inguinofemoral lymphadenectomy (eg, wound dehiscence, infection, lymphedema). The usual technique includes the use of technetium 99 (99mTc) plus blue dye, but if a near-infrared camera is available for detection, indocyanine green may be used in select patients (eg, patients with a low body mass index) [52].

Representative studies regarding SLNB for vulvar cancer include:

A systematic review and meta-analysis of 29 observational studies included 1779 patients with mostly stage IB or II vulvar cancer [53]. In 12 studies using both 99mTc/blue dye, ultrastaging, and immunohistochemistry with inguinofemoral lymphadenectomy as the reference standard, SLNB had a pooled sensitivity of 95 percent (95% CI 92 to 98 percent) and a negative predictive value of 97.9 percent.

The GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I was a prospective study in which 403 patients with stage I or II (tumor size <4 cm) vulvar squamous cell carcinoma had SLNB with a combination of 99mTc and blue dye [54]. If SLNB was performed and was negative (n = 276), no lymph node surgery was performed. If an SLNB was positive or no sentinel lymph nodes were identified, inguinofemoral lymphadenectomy was performed. With a median follow-up of 35 months, the groin recurrence rate in patients with a negative SLNB was 3 percent, which is similar to the historical recurrence rate following inguinofemoral lymphadenectomy [12,32,37,38,55-58].

A long-term update of the GROINSS-V I trial showed a groin recurrence rate of 2.5 percent for SLNB-negative patients at five years, with a 10-year disease-specific survival (DSS) of 91 percent in this group of patients [59]. The 10-year DSS was 65 percent in SLNB-positive patients.

Results of the GROINSS-V II/GOG-270 trial suggest that those with negative SLNB may be able to avoid further treatment; those with micrometastases may have acceptably low recurrence rates with adjuvant radiation alone, rather than lymphadenectomy; and those with macrometastases to the sentinel lymph node (SLN) would benefit from lymphadenectomy (followed by radiation if more than one SLN was involved or extranodal extension was present). In preliminary results, among 1222 patients with SLNB-negative vulvar cancer, isolated groin recurrences occurred in approximately 3 percent of patients [60]. This trial also included 322 patients with positive sentinel nodes, approximately one-half of whom had micrometastases (≤2 mm) and one-half of whom had macrometastases (>2 mm) [51]. Among the 160 patients with SLN micrometastases, 126 received inguinofemoral radiotherapy, among whom the ipsilateral isolated groin recurrence rate at two years was 1.6 percent. Among the 162 patients with sentinel node macrometastases, the isolated groin recurrence rate at two years was 22 percent in those who underwent radiotherapy, and 6.9 percent in those who underwent lymphadenectomy, the majority of whom (56 percent) also received adjuvant RT.

Eligibility criteria for SLNB are still evolving. The issue regarding the risk of groin recurrence with tumors ≥2 cm requires further investigation, since data are limited to one small study [61]. Among the authors and editors of this topic, most offer SLNB to patients with vulvar cancer who meet GROINSS-V criteria and a few additional criteria:

Tumor diameter <4 cm

>1 mm depth of invasion

No palpable groin lymph nodes

Unifocal disease

Surgeon has sufficient expertise (has performed >10 SLNB procedures under supervision)

However, a more conservative approach is reasonable and is used in some institutions, with SLNB offered only to patients with tumor diameter <2 cm.

In terms of technique, a 2015 systematic review and guidelines published by Cancer Care Ontario examined the various approaches of detecting lymph node metastases in vulvar cancer [62]. The overall detection rate with a combination of radiocolloid and blue dye as assessed in 18 studies was 86.9 percent, and the false-negative rate from a meta-analysis of 25 studies was 6.6 percent. The recurrence rate for negative sentinel nodes was 3.4 percent. The group recommended that for appropriate detection of sentinel nodes, radiocolloid tracers should be used alone or with blue dye. When lymphoscintigraphy does not identify a sentinel node, blue dye should be used. Use of Lymphazurin alone was discouraged due to low detection rates. The authors also recommended four quadrant intradermal injections into normal tissue at the tumor margins. They also suggested experience with 10 cases of SLNB followed by inguinofemoral dissection before performing SLNB alone, to overcome the technical challenges associated with the technique. The technique of SLNB is similar to that used for breast cancer [62]. (See "Sentinel lymph node biopsy in breast cancer: Techniques".)

SLNB may also be useful in identifying patients with a laterally ambiguous or midline tumor that may not require a bilateral groin lymphadenectomy. In a separate analysis of GOG-173, SLNB showed there was a lower frequency of bilateral nodal drainage as the lesion moved from midline to laterally ambiguous to a lateral position (70, 58, and 22 percent, respectively) [63]. Among patients with a laterally ambiguous (n = 27) or midline (n = 32) tumor who demonstrated unilateral drainage patterns on SLNB, no contralateral sentinel nodes were identified. However, contralateral groin lymphadenectomy demonstrated positive nodes in four patients with a midline tumor (13 percent), though none were identified among those with a laterally ambiguous tumor. Therefore, while patients with a midline tumor should undergo bilateral inguinofemoral lymphadenectomy, an SLNB may be useful to select patients with a laterally ambiguous tumor who may be safely treated with a unilateral lymphadenectomy instead.

Palpable groin nodes on examination — Patients with palpable inguinofemoral nodes on examination should undergo a lymph node biopsy to confirm nodal metastases.

Subsequent surgical approach depends on the results of lymph node biopsy, which can be performed in the office as a fine needle aspiration or in the operating room at time of other surgical evaluation and treatment:

If nodes are positive, we do not proceed with lymphadenectomy and instead plan adjuvant therapy including radiation to the groin. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Adjuvant therapy for surgically resectable disease'.)

This is due to the substantially increased morbidity associated with full lymphadenectomy and groin RT over groin RT alone [64]. Therefore, if it is known at the time of surgery that groin RT is necessary because of palpable, involved nodes, we prefer to resect those nodes only and include the groin in our adjuvant radiation fields. Limited data suggest that removal of only clinically involved nodes results in similar overall and disease-free survival compared with a full inguinofemoral lymphadenectomy, provided adjuvant RT is administered [64,65].

If the frozen section reveals no evidence of malignancy in the lymph nodes, we proceed with lymphadenectomy and offer adjuvant radiation, if indicated, based on the results of the final pathology. Of note, 24 to 41 percent of those with clinically enlarged nodes are negative at histological examination [36-38]. This is likely due to reactive changes from a superficial infection or the occurrence of necrosis at the primary site.

Nodal debulking — For patients who present with palpable groin lymphadenopathy on examination and are candidates for surgery, it is our practice to perform vulvar excision with nodal debulking.

Patients who are not candidates for surgery due to disease extent (eg, groins fixed to the femoral vessels) should proceed with primary chemoradiation. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Unresectable, locally advanced disease'.)

ADJUVANT THERAPY — For patients who do undergo a surgical resection of disease, risk of recurrence may be decreased with adjuvant therapy. This is discussed in detail separately. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Adjuvant therapy for surgically resectable disease'.)

DISEASE THAT CANNOT BE MANAGED SURGICALLY — The management of patients with unresectable disease is discussed separately. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Disease that cannot be managed surgically'.)

POST-TREATMENT SURVEILLANCE — Post-treatment surveillance is discussed in detail separately. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Post-treatment surveillance'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vulvar cancer and vaginal cancer".)

SUMMARY AND RECOMMENDATIONS

Histology – Vulvar cancer is the fourth most common gynecologic cancer in high-resource countries. Most vulvar cancers are squamous cell histology. (See 'Introduction' above.)

Staging – Vulvar cancer is staged using a hybrid of clinical and surgical findings. The International Federation of Gynecology and Obstetrics (FIGO) staging system is presented in the table (table 1). Tumor size and depth of invasion are determined mostly on physical examination and vulvar biopsy, and lymph nodes are evaluated by physical examination, imaging, and lymphadenectomy or sentinel lymph node biopsy (SLNB). (See 'Staging system' above.)

Vulvar excision – Excision of the primary vulvar lesion is performed by radical local excision, if feasible. Large, central, or multicentric lesions may require modified radical vulvectomy (figure 2). Resection of only involved tissue with an adequate margin conserves vulvar anatomy and aids wound healing. (See 'Vulvar excision' above.)

Lymph nodes evaluation and management – Evaluation or management of lymph nodes is determined primarily by whether there are clinically palpable inguinofemoral nodes on physical examination. (See 'Inguinofemoral lymph nodes' above.)

Patients with stage IA disease and no palpable inguinofemoral nodes require surgical resection of the primary lesion alone, with no lymphadenectomy.

For patients with stage IB to II disease who are at low risk for lymph node metastases (lesions <2 cm, lateral, no palpable nodes), we suggest a unilateral (ipsilateral) lymphadenectomy or SLNB rather than bilateral lymphadenectomy (Grade 2C). Bilateral lymphadenectomy is performed for patients with palpable lymph nodes and other factors (lesions 2 cm, central, and/or local extension).

More data are needed regarding selection criteria for SLNB in terms of the upper limit of tumor size and the risk of groin recurrence. Many institutions also offer SLNB to patients with a tumor diameter up to <4 cm. (See 'Unilateral versus bilateral' above.)

Patients with palpable inguinofemoral nodes do not undergo complete lymphadenectomy and are typically managed with a debulking procedure for the inguinofemoral nodes.

Treatment of positive or narrow margins – For patients with tumor at or close to the surgical margins (≤8 mm) identified at final pathologic analysis, we suggest re-excision to ensure complete resection, rather than observation (Grade 2C). For those patients who do not want or cannot undergo repeat surgery, limited data suggest that radiation therapy is a reasonable alternative, especially when further surgery could compromise the function of adjacent midline structures (clitoris, vagina, anus). (See 'Treatment of positive or narrow margins' above.)

Role of other treatments – Chemotherapy and radiation for vulvar cancer, both as adjuvant treatment as well as primary treatment for disease that cannot be surgically resected, are discussed separately. (See "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Adjuvant therapy for surgically resectable disease' and "Squamous cell carcinoma of the vulva: Medical therapy and prognosis", section on 'Disease that cannot be managed surgically'.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to recognize John C Elkas, MD, JD, and Anthony H Russell, MD, who contributed to an earlier version of this topic review.

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References

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