Carcinoma of the Vulva - Treatment

Contents

VIN III

The optimal treatment is by surgical excision. Laser is not encouraged because its primary use is to preserve the basement membrane, to facilitate wound healing. However, the dysplastic cells arise from the basement membrane. This would suggest that laser can never adequately treat VIN where the basement membrane is preserved. Clinical evidence suggests otherwise. It is speculated that the successful treatment of the VIN by laser may involve the action of growth factors and cytokines released in the vicinity. The use of laser may be appropriate in trying to preserve the clitoris or other vital vulval anatomy. 5-FU cream has been used where there is extensive disease or where surgical removal is difficult or undesirable. Where there is extensive VIN, consideration should be given to a "skinning" or superficial (non-radical) vulvectomy with placement of a skin graft. On occasions, the use of plastic surgery flaps and other techniques may be necessary to cover the defect left by surgical excision of VIN.

Early Vulval Cancer 

Patient requires a radical local excision or radical hemivulvectomy. If the cancer is bilateral and multifocal, a radical vulvectomy is required. If the cancer is associated with extensive VIN or extensive vulval dystrophy, consideration given to radical vulvectomy. The surgical objective is to obtain at least a 1 cm clinical margin around the primary lesion, and ideally a 1.5 cm margin (2). The resection should involve the full thickness of the vulva down to the deep fascia of the urogenital diaphragm or the musculature of the leg, underlying the circumscribed cutaneous resection. 

Stage IA: 

nodes clinically negative: No inguino-femoral lymphadenectomy required.

Stage IB and II:

 Inguino-femoral lymphadenectomy is required. In the case of Stage IB disease, the inguino-femoral lymphadenectomy can be deferred until after histological quantitation of the depth of invasion confirms >1mm invasion.

Inguino-femoral lymphadenectomy entails resection of all the fibro-fatty-lymphatic tissue between the superficial and deep fascia overlying the femoral triangle extending 2 cm cephalad to the inguinal ligament, plus removal of all the femoral nodes adjacent to the femoral vein and within the fossa ovalis. Resection of saphenous vein in continuity with this tissue is optional. 

Inguino-femoral lymphadenectomy is bilateral in all cases except well lateralized T1 and T2 lesions on the labium majus (3). If primary lesion is within 2 cm of the posterior fourchette or clitoris/urethra then bilateral groin node resection is required. Separate incisions for resection of primary disease and lymphadenectomy are recommended but not mandatory. This has been proven to decrease wound breakdown and perioperative morbidity with no compromise in survival (4).

Clinically Suspicious Groin Nodes.

These patients require pre-operative CT scan of the groins, pelvis and abdomen. The primary disease is managed according to the principles outlined above. The macroscopically enlarged or suspicious lymph nodes are resected and submitted for frozen section to confirm histological status. If no evidence of disease on frozen section, standard inguino-femoral lymphadenectomy is completed. Otherwise all macroscopically enlarged nodes are removed in the expectation that post-operative radiotherapy will be administered. By preserving some clinically uninvolved fibro-fatty-lymphatic tissue, there is a lower incidence of lymphoedema at the completion of treatment.

If there is imaging evidence of pelvic lymphadenopathy, an extra-peritoneal pelvic lymph node debulking is performed at the time of groin node surgery. The superior skin flap is retracted cephalad and an incision made through the rectus fascia 2 cm above and parallel to the inguinal ligament. The underlying muscles are divided and separated allowing access to the retroperitoneum. Bulky lymph nodes are then systematically resected.

Fixed or Ulcerated Groin Nodes.

If there is a realistic expectation of resection of all macroscopic disease with surgery, then this is the preferred treatment. Such surgery can be difficult and option of vascular bypass grafting or myocutaneous transposition flaps may need to be considered. Following surgery the affected groin requires treatment consolidation with radiotherapy. If primary surgery is not feasible, treat with primary radiotherapy. At completion of radiotherapy, options include surgery or expectant follow-up.

Advanced Primary Tumour

T3 Lesions

Lesions extending to the distal urethra may be resected with a 1+ cm margin by resecting the distal urethra. Up to 1.5 cm (or the distal 1/3) of distal urethra can be resected with minimal effect on urinary continence. The greater the resection beyond this extent, the greater the incidence of incontinence. If there is disease involving the distal anus, rarely can an adequate margin around the primary tumour be obtained without compromising rectal continence. These patients all require bilateral inguino-femoral lymphadenectomy.

There is a place for exenterative surgery in selected cases. The adjacent viscera may be sacrificed and the primary cancer resected en bloc with bladder or rectum.

Where viscera-preserving radical vulvectomy surgery does not provide an adequate margin around the primary disease, consideration is given to preoperative (chemo-) radiotherapy. Groin node dissection can be completed prior to this therapy and is not associated with significant delays in treatment. This treatment technique is associated with very good survival rates and avoids the need for a stoma. At the completion of radiotherapy, consideration should be given to resection of the tumour bed to exclude the presence of persisting disease. 

T4 Lesions

Management of patients with this extent of disease is highly individualized taking into account the patient's age and medical condition, the extent and distribution of disease, the likelihood of cure.

Options for treatment include:-

1. Exenterative surgery with radical vulvectomy and groin node dissection
2. Preoperative (chemo-)radiotherapy followed by surgery
3. Surgery followed by (chemo-)radiotherapy

Post-operative Treatment

Positive or Close Surgical Margins (<1cm)

Treatment is individualized, but options include:-

1. Observation (if margin negative)
2. Reoperation 
3. (Chemo-) radiation of the primary surgical site.

N0 Lesions

Patients with N0 disease who refuse or are unfit for groin dissection can be treated with inguino-femoral (chemo-)radiotherapy. With modern anaesthetics and peri-operative care there are very few patients who are truly unfit for surgery. There is a randomized trial comparing primary radiation and primary surgery in the management of groin nodes. This demonstrated a superior outcome for patients managed surgically (7). With the utilization of pre-treatment CT scan of the groin to determine nodal depth and to plan treatment, it is possible that the results for radiotherapy would be better.

N1 and N2 Lesions

Where there is a single lymph node involved with microscopic metastatic disease, no adjuvant treatment is required.

Where there are 2 or more microscopically positive lymph nodes or 1 or more macroscopically positive lymph nodes, or a single node with significant extra-capsular spread, for bilateral groin plus whole pelvic radiotherapy (5).

Recurrent Disease

15-40% of patients develop recurrent disease. 70% of these patients will have local disease with 55-90% of these being an isolated local recurrence. Aggressive management of patients with an isolated local recurrence is associated with prolonged survival and quality of life.

Vulval Melanoma

Vulval melanoma is the 2nd commonest vulval malignancy. The most important aspect of treatment is adequate radical resection of the primary lesion. There are limited data regarding the extent of resection margin, however a 1-2cm margin is widely quoted as adequate.

The role of inguino-femoral lymphadenectomy is contentious. Some argue that if nodes are negative then resection is unnecessary and if positive, the prognosis is so poor and adjuvant treatments so ineffective that the surgical intervention cannot be justified.

The contrary view is that the nodal status provides important prognostic information and is associated with minimal morbidity. Furthermore, this will often provide local disease control even if there is a high risk of distant failure. Finally, these patients can be offered investigational protocols such as vaccine therapy.

T1A and B Clitoral Lesions in Young Women

1. The conventional treatment of this lesion is radical local excision +/- bilateral inguino-femoral lymphadenectomy (depending on depth of invasion). This is associated with significant psychosexual morbidity. These patients may be offered an investigational protocol consisting of chemo-radiation to the primary lesion with preservation of the clitoris (6). The groin nodes are managed using a conventional surgical approach. There are several patients treated in the unit who have been successfully managed in this manner and are being followed long term. 
   

Radiotherapy Guidelines

The total dose and the dose per fraction, depends on the volume irradiated and whether concomitant chemotherapy is used. In general, the lower of the total dose options is used if concomitant chemotherapy is used. The dose per fraction recommended is between 1.6-1.8 Gy with the lower dose per fraction preferred when using concomitant chemotherapy.

Dose

Subclinical Disease (Adjuvant radiotherapy)

45-50 Gy in 1.6-1.8 Gy per fraction.

Positive Margins/Gross Residual Disease

45-50 Gy in 1.6-1.8 Gy per fraction to large volume then boost macroscopic disease to 54-60 Gy in 1.6-1.8 Gy per fraction.

Pre-Operative 

45-50 Gy in 1.6-1.8 Gy per fraction followed by surgery 4-6 weeks later.

Definitive Radiotherapy

45-50 Gy in 1.6-1.8 Gy per fraction to large volume them boost macroscopic disease to 54-60 Gy in 1.6-1.8 Gy per fraction.

Chemoradiation

Options include:-

1. Cisplatin 40mg/m2 per week
2. Cisplatin 80mg/m2 D1 or 40 mg/m2 D1 and D2 plus 5FU 800mg/m2/day IV infusion for 4 days (96 hrs) in first and fifth week of radiation.

Femoral neck tolerance 42-47 Gy

Technique

The patient is treated supine with hips abducted to reduce groin folds, eg feet in stocks.

CT planning is essential to define the depth of the inguino-femoral nodes.

Primary (vulva) portals should be by radiotherapy portals that encompass the primary tumour with a 20mm margin. If unifocal disease in the vulva, a direct perineal portal may be used and the whole vulva does not need to be included. A mega-voltage photon field with appropriate bolus to ensure surface dose, or an energy electron field may be used. 

If more extensive vulvar disease, the whole vulva will need to be included, usually via AP/PA coaxial opposed portals using mega voltage photons.

For inguinal and pelvic nodal treatment, the superior margin of the radiation volume is at the level of the mid-sacroiliac joint (ie just below the common iliac bifurcation). The inferior and lateral margins of the radiation volume are determined clinically. This volume can be encompassed by mega voltage photon AP/PA parallel ports utilizing a tissue compensator to shape the treatment volume as defined by CT scan. Other options include using biased fields, a large anterior field covering the pelvis and inguinal nodes with a small posterior field to boost the pelvic nodes and anterior electron fields to boost the inguino-femoral nodes, keeping to within the femoral neck tolerance of 42-47 Gy.

Sites of bulky disease can be boosted with direct electron or photon fields using appropriate bolus.

Interstitial implants or intracavitary brachytherapy eg. Intravaginal cylinder for vaginal extension, may be used as a boost. 

References

1. Clinical Practice Guidelines. Management of Gynecologic Cancers. Volume1, No. 1, 1996
2. Heaps JM, Fu YS, Montz FJ et al. Surgico-pathological variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynaecol Oncol 1990; 38: 309.
3. Iversen T , Abeler V, Aalders J: Individualized treatment for stage I squamous cell vulvar carcinoma. Obstets Gynecol 1984;63,155.
4. Hacker NF, Leuchter RS, Berek JS, et al. Radical vulvectomy and bilateral inguinal lymphadenectomy through separate groin incisions. Obstets Gynecol 1981;58,574.
5. Homesley HD, Bundy BN, Sedlis A, Adcock L: Radiation therapy versus pelvic lymph node resection for carcinoma of the vulva with positive groin nodes. Obstets Gynecol 1986;68,733.
6. Jones RW and Matthews JH. Early clitoral carcinoma successfully treated by radiotherapy and bilateral inguinal lymphadenectomy. Int J Gynecol Cancer 1999;9,348.
7. Stehman FB, Bundy BN, Thomas G, et al: Groin dissection versus groin irradiation in carcinoma of the vulva: A Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys 1992;24,389-396.

Dr James L. Nicklin
M.B., B.S. (Qld), F.R.A.C.O.G., C.G.O
Gynaecologic Oncologist
Queensland Centre for Gynaecological Cancer

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