HOLLYWOOD, FLA. – The National Comprehensive Cancer Network has issued new guidelines for the diagnosis and management of vulvar cancer.

Vulvar cancers are rare neoplasms, with an estimated U.S. annual incidence of 5,950 cases, and 1,110 deaths. The majority of cases (about 90%) are of squamous cell histology.

Treatment of vulvar cancer has evolved from en bloc resections used throughout most of the 20th century, to more refined techniques, said Dr. Benjamin E. Greer , professor of gynecological oncology at the University of Washington in Seattle.

“In the 1980s, we started to modify treatment to reduce morbidity,” he said at the annual conference of the National Comprehensive Cancer Network.

With older, more radical techniques, groin breakdown, leg edema, and impaired sexual function were common post-surgery consequences. Current practice, however, is to perform regional lymph node management for unilateral cancers, radical local excision rather than en bloc resections, separate groin incisions, lymphatic mapping, radiation, chemotherapy, and, if necessary, exenteration, Dr. Greer noted.

The guidelines note that adequate surgical margins – 1 to 2 cm – at the time of primary surgery appear to be essential for reducing risk of local recurrence, and that if margins are within 8 mm of tumor, the surgeon should consider re-excision or adjuvant radiation.

Lymph node status is the most important determinant of survival, with historical reports showing overall survival following surgery of 70% to 80% among patients with negative nodes, compared with 30% to 40% of those with positive nodes, he said.

Evaluation of bilateral inguinofemoral groin nodes should be performed in patients with lesions in the vulvar midline, and ipsilateral groin node evaluation should be performed for those with lateral lesions lying more than 2 cm from the vulvar midline. Additionally, select patients may require sentinel lymph node biopsy, the guidelines state.

Unilateral carcinomas of the vulva can be treated with limited radical vulvectomy and ipsilateral inguinal femoral node dissection. Lymph node dissection can be performed through a separate incision. For patients with positive nodes, adjuvant radiation may aid in disease control. Patients with inoperable carcinomas are recommended to receive radiation and chemotherapy.

Radiation for vulvar cancer

“For early stage tumors, adjuvant radiotherapy is an effective treatment modality that significantly decreases recurrence, especially in surgically resected groins, and it leads to improvement in relapse-free and overall survival,” said Dr. Wui-Jin Koh , medical director for radiation oncology at the Fred Hutchinson Cancer Research Center in Seattle.

Concurrent chemotherapy and radiation may provide additional therapeutic benefit, especially for patients with advanced, unresectable tumors, and it may help to address systemic risk in patients with multiple positive lymph nodes, Dr. Koh said.

The guidelines state that radiation can be given with external beam radiation delivered via a 3D-conformal or intensity modulated (IMRT) technique, with brachytherapy boost for some tumors where the anatomy permits.

“Careful attention should be taken to ensure adequate tumor coverage by combining clinical examination, imaging findings, and appropriate nodal volumes at risk to define the target volume,” the guideline states.

For adjuvant therapy, doses of 50.4 Gy divided in 1.8 Gy fractions should be delivered once daily 5 days per week, with minimal treatment breaks.

For treatment of unresectable tumors, doses range from 59.4 Gy to 64.8 Gy in 1.8 Gy fractions, with a boost dose to approximately 70 Gy for large lymph nodes in select cases.

Residual disease

The decision to provide additional treatment following surgery is based on whether the patient is clinically negative for residual tumor at the primary site and nodes.

“If one has negative margins and negative nodes? Observation, absolutely,” Dr. Koh said. “If one has positive margins for invasive disease, our recommendation is to re-excise and not go straight to radiation, and if one can do it and get negative margins, again observe the majority of them.”

“Use radiation very judiciously,” he added. “Only if patients have positive margins or have unresectable primary disease do we routinely recommend radiation.”

Locally advanced disease

For patients who cannot be treated with conventional or sphincter-sparing, organ preserving surgery upfront, the recommendation is to provide chemoradiation, with initial radiation to the primary site, groins, and pelvis, and concurrent week cisplatin at a dose of 30-40 mg/m2 per week. The recommended radiation doses are 45 Gy to at-risk, microscopic clinical tumor volume, and 57.6 to 60 Gy to gross tumor volume (primary site and nodes).

“If one uses IMRT, you need to be very generous with the volumes,” Dr. Koh said.

The panelists also recommend re-imaging and re-evaluating patients 6 to 8 weeks after the completion of chemoradiation, with possible resection or biopsy of the primary tumor site, and limited groin resection of imaged residual disease.

For patients with clearly node-positive disease, “my general preference is to give upfront chemoradiation therapy to avoid delay of primary therapy, and then resect residual nodes after the chemoradiation is done,” he said.