What are the management options for vulvar cancer?

Vulvar Cancer Management

Surgery is the cornerstone of vulvar cancer management, with treatment determined by stage, tumor size, location, and depth of invasion, followed by adjuvant radiation therapy ± chemotherapy for node-positive disease. 1, 2

Stage IA Disease (≤1 mm Invasion)

• Perform wide local excision only with observation—no lymph node evaluation is required due to <1% risk of lymphatic metastases 1, 2
• If final pathology reveals >1 mm invasion in aggregate, proceed to additional surgery for lymph node assessment 1, 2

Stage IB-II Disease (>1 mm Invasion)

Surgical Approach Based on Tumor Location

For lateral lesions (≥2 cm from vulvar midline):

• Perform radical partial vulvectomy or modified radical vulvectomy targeting 1-2 cm margins 1, 3, 2
• Resection depth should extend to the urogenital diaphragm 1, 2
• Conduct ipsilateral inguinofemoral lymph node evaluation only 1, 3
• A negative unilateral lymphadenectomy carries <3% risk of contralateral metastases 1, 3

For central or near-midline lesions (<2 cm from midline):

• Perform radical partial vulvectomy or modified radical vulvectomy 1, 3
• Conduct bilateral inguinofemoral lymph node evaluation due to risk of contralateral lymphatic spread 1, 3

Lymph Node Assessment Strategy

Sentinel lymph node (SLN) biopsy is the preferred initial approach when ALL criteria are met: 1, 3, 2

• Unifocal tumor <4 cm in diameter 1, 3, 2
• Clinically and radiologically negative groin nodes 1, 3, 2
• No previous vulvar surgery that disrupted lymphatic drainage 1, 3, 2
• High-volume SLN surgeon available 1, 2

Technical requirements for SLN biopsy:

• Use dual tracer technique (technetium-99m radiocolloid plus blue dye such as Isosulfan Blue 1%) for optimal detection 1, 3
• Inject radiocolloid 2-4 hours prior to surgery 1
• Inject approximately 3-4 cc of blue dye 1
• If SLN is not detected, proceed immediately to complete inguinofemoral lymphadenectomy 3, 2

SLN biopsy reduces lymphedema risk to approximately 5% compared to 30-70% with complete lymphadenectomy 1, 3

If SLN criteria are not met, proceed directly to complete inguinofemoral lymphadenectomy (superficial inguinal and deep femoral nodes through separate incisions) 1, 2

Management Based on Nodal Status

If lymph nodes are negative:

• Observe if margins are adequate (≥8 mm) 1
• Consider adjuvant radiation to primary site based on other risk factors: lymphovascular invasion, close margins (<8 mm), large tumor size, depth of invasion >5 mm 1, 4

If lymph nodes are positive:

• Postoperative radiation therapy to the groins is mandatory—this significantly decreases recurrence and improves survival 1, 3, 2
• Add concurrent platinum-based chemotherapy for high-risk features: multiple positive nodes, extranodal extension, or bulky nodal disease 3, 2
• Chemotherapy options include cisplatin alone, 5-FU + cisplatin, or 5-FU + mitomycin C 3, 2
• Recommended radiation dose is 50.4 Gy in 1.8 Gy fractions 2
• Initiate adjuvant treatment within 6-8 weeks post-surgery once adequate healing is achieved 3, 2

If unilateral lymphadenectomy reveals positive nodes:

• Perform contralateral lymphadenectomy OR radiation of the contralateral groin 1
• Evaluate any grossly enlarged or suspicious nodes by frozen section intraoperatively to tailor extent and bilaterality of dissection 1

For SLN metastasis ≤2 mm:

• Postoperative radiotherapy alone is safe (2-year isolated groin recurrence rate of 1.6%) 4

For SLN metastasis >2 mm:

• Complete inguinofemoral lymphadenectomy followed by postoperative radiotherapy is required (radiotherapy alone results in unacceptably high 22% 2-year groin recurrence rate) 4

Margin Management

If margins are positive or close (<8 mm):

• Re-excision is preferred if feasible without significant morbidity 1
• Adjuvant local radiation therapy is an alternative 1
• Do not re-excise margins involving urethra, anus, or vagina if this would cause significant morbidity or adverse impact on quality of life 1
• Re-resection may not be beneficial in patients with positive nodes who will receive radiation therapy anyway 1

Stage III-IVA Disease (Locally Advanced)

Primary chemoradiation is the preferred approach to preserve organ function and avoid exenterative surgery: 1, 2, 5

• Recommended radiation dose is 59.4-64.8 Gy in 1.8 Gy fractions for unresectable disease 2
• Administer concurrent platinum-based chemotherapy (cisplatin alone, 5-FU + cisplatin, or 5-FU + mitomycin C) 2, 5
• Use 3D conformal or IMRT to ensure adequate coverage while minimizing toxicity 2
• Brachytherapy boost can be used for anatomically amenable primary tumors 2
• Minimize treatment breaks and aggressively manage acute toxicities 2

If complete response is not achieved after chemoradiation:

• Surgical resection of residual disease is recommended in patients with resectable disease who are appropriate surgical candidates 1

For bulky inguinofemoral lymph nodes with unresectable or T3 primary tumor, consider either: 1

• Primary cytoreductive surgery of bulky nodes followed by platinum-based chemoradiation to bilateral groins and primary tumor, OR
• Platinum-based chemoradiation to bilateral groins and primary tumor alone 1

Stage IVB Disease (Distant Metastases) and Recurrent Disease

Systemic chemotherapy options include: 2, 6

• Cisplatin alone 2, 6
• Cisplatin + vinorelbine 2
• Cisplatin + paclitaxel 2
• 5-fluorouracil + cisplatin 6

For recurrent disease, treatment depends on location and prior therapy: 6

• Lateralized local vulvar recurrences: Wide radical local excision with inguinal lymphadenectomy (70% cure rate) 6
• Central pelvic recurrence with prior radiation: Total pelvic exenteration in select patients 6
• Inguinal recurrences without prior radiation: Excision followed by radiotherapy with chemosensitization 6
• Inguinal recurrences with prior radiation: Avoid excision due to high complication rate; offer brachytherapy for palliation 6
• Pelvic recurrences: Chemoradiation is the treatment modality 6

Imaging for Staging and Surveillance

At initial diagnosis: 1

• Imaging is useful to assess size and extent of primary tumor 1
• Evaluate status of inguinofemoral lymph nodes 1

For suspected recurrence: 1

• Imaging is essential to demonstrate local extent of tumor and identify lymph node and distant metastases 1
• Consider whole body PET/CT if not previously performed 1
• Consider pelvic MRI to aid in treatment planning 1

Surveillance schedule: 1

• Interval history and physical examination every 3-6 months for 2 years, every 6-12 months for 3-5 years, then annually 1
• Cervical/vaginal cytology screening as indicated 1
• Imaging and laboratory assessment (CBC, BUN, creatinine) as indicated based on symptoms or examination findings 1

Critical Pitfalls to Avoid

• Never omit lymph node evaluation in stage IB-II disease—the risk of lymphatic metastases exceeds 8% 1, 3
• Do not perform SLN biopsy if tumor is multifocal or >4 cm—proceed directly to complete lymphadenectomy 3, 2
• Avoid en bloc radical vulvectomy—modern separate incision technique reduces morbidity without compromising survival 1, 2
• Do not use primary groin radiation instead of surgery—this results in higher groin recurrence rates despite lower morbidity 3
• Groin recurrences are generally fatal—emphasizing the critical importance of adequate initial nodal management 7

Prognostic Considerations

Lymph node involvement is the most critical prognostic indicator: 7

• Node-negative patients: >80% 5-year survival 7
• Node-positive patients: <50% 5-year survival 7
• Patients with ≥4 positive nodes: 13% 5-year survival 7

Surgical margin adequacy significantly impacts outcomes: 7

• Negative margins: 82% 4-year recurrence-free rate 7
• Close margins (<8 mm): 63% 4-year recurrence-free rate 7

Recurrence risk is highest in the first 2 years post-treatment, but nearly one-third of relapses occur after 5 years, necessitating long-term surveillance 7