Agreed 2009
Review 2012
MEDICAL PROTOCOL
ONCOLOGICAL MANAGEMENT OF VULVAR
CANCER
These guidelines have been developed by members of the Gynaecological
Oncology Guidelines Group, for approval by the Merseyside and Cheshire
Gynaecological Cancer Network Group.
1. Background...................................................................................................................... 3
2. Diagnosis and Referral ..................................................................................................... 4
3. Staging ............................................................................................................................ 5
4. Prognostic factors ............................................................................................................ 5
5. Pre-treatment assessment ................................................................................................ 6
6. Treatment ........................................................................................................................ 6
7. Surgery ............................................................................................................................. 7
Surgery in early disease: ................................................................................................... 7
Vulvo-vaginal Melanoma .................................................................................................... 8
Surgery in advanced disease: ............................................................................................ 9
8. Radiotherapy.................................................................................................................. 10
I. Primary Radiotherapy ................................................................................................... 10
II. Adjuvant Radiotherapy................................................................................................. 10
III. Palliative Radiotherapy ............................................................................................... 11
IV. Irradiation of Inguinal Nodes....................................................................................... 11
9. Chemoradiation.............................................................................................................. 11
10. Chemotherapy ............................................................................................................. 12
11. Treatment at Relapse .................................................................................................. 12
12. Hormone therapy .......................................................................................................... 12
13. Palliative Care and Nursing care ................................................................................... 13
14. Follow-up ..................................................................................................................... 14
15. Maintenance of Quality ................................................................................................ 14
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FIGO Staging Description ................................................................................................... 15
Appendix 1 .......................................................................................................................... 16
Radical Radiotherapy....................................................................................................... 16
Concurrent Chemoradiation ............................................................................................. 16
Palliative Radiotherapy dose schedules ........................................................................... 16
References ......................................................................................................................... 17
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1. Background
Vulvar cancer is an uncommon illness with fewer than 800 cases registered in the
UK each year. Hence most information about it comes from small personal series. In
establishing these guidelines we have drawn upon previously published guideline
texts, relevant published papers and chapters, and the recent RCOG publication,
“Clinical Recommendations for the Management of Vulvar Cancer”1
Ninety percent of all vulvar cancers are squamous in origin, histological type being of
importance because it is a variable affecting the likelihood of lymph node
involvement. Survival is closely related to lymph node involvement. For those without
any lymph node involvement 5-yr-survival is 80% but this falls to 50% if groin nodes
are involved and to 10-15% if iliac or other pelvic nodes are involved. Overall 30% of
patients presenting with vulvar cancer will be found to have nodal metastasis.
Multifactorial analysis shows that nodal status and the diameters of the primary
tumour are the only two variables which are associated with prognosis 2. These two
variables, of course, simply represent advancing stage of disease.
There is no screening test available for vulvar cancer although a number of
precursor lesions are recognised. These include Vulvar intraepithelial neoplasia
(VIN), and Paget’s disease of the vulva, and it is therefore appropriate to offer
women with these conditions long-term surveillance. Patients with lichen sclerosus
responsive to topical treatment may be discharged, but advised that they should
seek re-referral in the event of any symptomatic deterioration. It should also be
remembered that women who develop a vulvar cancer are at an increased risk of
developing other genital cancers, particularly cervix.
Surgery has been the treatment of choice for most women with vulvar cancer. Until
recently this has involved a radical vulvectomy combined with a bilateral groin node
dissection as popularised by Stanley Way in the 1950s. He clearly demonstrated the
superiority of such radical surgery over simple vulvectomy and hence this approach
came into use for virtually all vulvar cancers. An improved understanding of the
disease, its natural history and prognostic factors has recently led to a change in
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practice. Contemporary thinking emphasises individualisation of care and recognises
that it is possible to adhere to the important principles of wide excision of the primary
tumour and appropriate node dissection without performing a radical vulvectomy and
bilateral node dissection on all patients.
Another change in practice has been the introduction of combined modality therapy.
This includes the use of radiotherapy with or without chemotherapy. Significant
response can be achieved with well-planned radiotherapy, with or without
chemotherapy. This may be of particular importance in advanced disease or where a
tumour affects midline structures which are not amenable to surgical resection.
These guidelines will relate to all histological types of cancer occurring on the vulva.
2. Diagnosis and Referral
Early diagnosis is vital if survival is to be improved and the morbidity of treatment
reduced. Factors which may assist primary care doctors in making or suspecting a
diagnosis include the following:
a)
Vulvar cancer is a disease which is most frequent in elderly women
b)
Vulvar pain, burning, pruritus and soreness can all be associated with vulvar
cancer. However a lack of symptoms does not exclude invasive disease since
some tumours are asymptomatic.
c)
ANY vulvar symptom should prompt an examination of the lower genital tract.
d)
Warts are uncommon in elderly women and should be regarded with suspicion.
In pre-menopausal women “warts” may initially be treated as condolymata
accuminata but persistent warts should be referred for an excision biopsy.
It is recommended that referral should be made if any of the following changes are
detected:
a swelling, polyp, lump or ulcer
colour change- whitening or pigment deposition
elevation and/or irregularity or surface contour
a clinical “wart”
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irregular fungating mass
an ulcer with raised rolled edges
enlarged groin nodes
If invasive disease is suspected then the patient should be referred to a clinician with
an interest in vulvar disease, with a view to onward referral to the network
Gynaecological Oncology Centre if invasive cancer of any stage is confirmed. It is
important that relevant histological material should be sent to the specialist
gynaecological pathologist in the GOC.
Referrals should be made within the current rapid access time limits stipulated by
the Department of Health.
Diagnosis should in most cases be confirmed by a biopsy prior to definitive surgery.
Occasionally, where the clinical situation dictates, definitive surgery to the lesion
may be performed. In general, surgery to the groin nodes should not be performed
prior to pathological confirmation of invasive disease. If lesions are small (<2cm in
diameter) then it is sometime appropriate to excise the whole of the lesion as a
diagnostic biopsy. It is important to keep detailed notes regarding the site and size of
the lesion in case further treatment is required. It may be helpful to take a clinical
photograph prior to surgery in these circumstances, with the patient's express
consent.
3. Staging
This is perhaps the worst and most illogical staging system used in gynaecological
oncology. It is a clinical staging system except for the recent addition of stage 1a
which is a histological classification. It is hard to understand why a histological
approach could not have been introduced for lymph node involvement since this is
the most important prognostic factor. See Appendix 1.
4. Prognostic factors
The two factors which are significantly associated with prognosis are nodal
involvement and the size of the primary lesion2.
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5. Pre-treatment assessment
The most important investigation is a biopsy to confirm the diagnosis and assess
depth of invasion. Biopsies are normally representative although smaller lesions may
be completely excised. A representative biopsy should include an area of epithelium
where there is a transition from normal to abnormal tissue. Biopsies should be sent
for examination by a pathologist with a special interest in gynaecological oncology.
Other investigations may include:
 FBC
 Biochemical profile
 Chest X-ray
 appropriate imaging to assess extent of disease and nodal status - this may
include modalities such as Ultrasonography, CT or MRI scanning. Imaging of
pelvic nodes is indicated if the groin is clinically suspicious.
 Biopsy or FNA of clinically suspicious nodes or other metastases where the result
may alter management
6. Treatment
Although considerable change has taken place in the management of vulvar cancer
during the last decade, the principles of management remain unchanged. All
patients need assessment for:
1)
appropriate treatment for the primary site of disease
2)
appropriate treatment for potential lymph node metastases.
Since the presentation of vulvar cancer may vary enormously, each case needs to
be judged on its own merits. As alluded to above, treatment may involve surgery,
radiotherapy or chemotherapy and in some cases a combination of all three. There
is also an increasing use of plastic surgery techniques. This may lessen the surgical
morbidity by allowing closure of tissues without undue tension and could reduce
long-term psycho-sexual morbidity associated with the scarring that follows the
standard radical approach. Many factors will influence decisions regarding
management including the site and size of the primary tumour and its histological
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features, the presence or absence of nodal metastasis, the fitness of the patient and
her informed decision.
In these guidelines, the management of the primary tumour and the nodes will
discussed in turn. Furthermore, in order to refine the broad principles of treatment
into a management programme, two categories of disease, “early” and “advanced”
will be considered separately. These can be defined as:
Early Disease: Disease that is limited on clinical examination to the vulva with no
evidence of nodal metastasis.
Advanced Disease: Disease in which nodal metastasis is suspected and/or where
excision of the primary tumour would involve sacrifice of important midline
structures.
7. Surgery
Surgery in early disease:
Management of the primary tumour should involve a radical wide local excision. The
main aim of the surgery is to remove the primary tumour with minimum 1cm clinical
margins of disease-free tissue in all directions. This approach reflects evidence
demonstrating that the risk of local recurrence is related directly to the size of the
surgical excision margins3,4. Consideration should also be given to the removal of
adjacent areas of abnormal epithelium (e.g. VIN or Lichen sclerosus) since it is
possible that they could contain small, separate foci of invasion.
Surgery to assess the possibility of nodal metastasis is necessary in all cases except
1)
Stage 1a disease5.
2)
Basal cell carcinoma and verrucous carcinoma - rarely associated with
metastasis6,7.
3)
Malignant melanoma - no evidence of any nodal involvement8.
In most cases bilateral groin node dissection will be required because of the
extensive crossover of lymphatic channels in the vulva. However in very lateral
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tumours whose medial edge lies at least 2 cm from the midline ipsilateral groin node
dissection may be performed initially, with recourse to dissection or irradiation of the
contralateral nodes if the ipsilateral histology is positive. Surgery can be carried out
by the “triple incision” technique described by Hacker9 since the incidence of skin
bridge recurrence in early-stage disease is very low. It is recommended that
superficial groin nodes as well as deep femoral nodes are removed as the removal
of superficial nodes alone is associated with a higher risk of groin node recurrence 10.
Recent research indicates that it is possible to accurately predict nodal metastasis
using sentinel node biopsy in patients with early vulvar cancer (<4cm) 11. A. Van der
Zee et al performed sentinel node procedure on 623 groins, they found that
recurrence rate was low (n=6) and survival excellent and treatment related morbidity
minimal. A large RCT is due to commence within the next 12 months. Until then
sentinel node biopsy should only be performed as part of a trial and after appropriate
training of the team involved.
Another method of follow up for patients who have declined groin dissection or been
deemed unfit for surgery is a combination of ultrasonography and fine needle
aspiration and cytology12. At LWH over the last 4 years have assessed 40 patients
with a positive predictive rate of 100%, and we have had one patient who developed
a groin recurrence 6 months after initial treatment.
Vulvo-vaginal Melanoma
The risk of recurrence and therefore survival in vulval melanomas is mostly related
to size of the tumour and the depth of invasion. The management of the groin nodes
in melanoma is controversial and has little effect on survival but may provide local
control of the groins. Thus, if nodes are palpable then they should be removed.
There is however no indication for groin dissection when the depth of invasion is less
than .76mm as the risk of metastasis is almost zero. For patients with a depth of
invasion between 1mm and 4 mm but without palpable nodes, ultrasonography and
fine needle aspiration can be offered. The role of sentinel node in this group has yet
to be decided. Interestingly the role of cutaneous melanoma in this specific group
has shown a survival advantage with sentinel node biopsy (MSLT-1).
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New cases of vulvovaginal melanoma should be referred to the gynaecological
MDT, who will in turn notify the network melanoma MDT with a view to arranging
combined management as indicated by each individual presentation.
Surgery in advanced disease:
The principles of surgery are unchanged in that wide excision of the disease with at
least 1cm clinical margins is the aim. The surgery required will of course depend
upon the size and site of disease and the involvement of any important midline
structures. Primary radiotherapy or chemoradiation is advised when surgery might
be significantly morbid, and in some patients may remove the need for surgery
altogether if a complete response is achieved. Two studies have suggested that preoperative chemoradiation can reduce the need for defunctioning stomas 13,14. Clearly
the surgery required for advanced disease will be more radical than for early disease
and more likely to involve radical vulvectomy or even exenterative surgery with the
formation of faecal stomas or urinary conduit where necessary. The size of the
deficit left behind after removing the primary tumour may also be more difficult to
close by primary closure. It is therefore appropriate to consider using reconstructive
surgical techniques in some cases. These procedures may be performed by the
gynaecological oncologist or in conjunction with plastic surgery colleagues
depending upon the procedure required.
Groin node dissection is appropriate in all cases of late disease unless there are
fixed and/or ulcerated groin nodes present. In these circumstances the involvement
of the nodes should be confirmed by biopsy (open, trucut or FNA). The appropriate
treatment options include palliative radiotherapy or radical treatment using
radiotherapy +/- chemotherapy with surgery later if there is good response to
treatment.
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8. Radiotherapy
For early stage, surgery is the treatment of choice. Radiotherapy given alone or in
conjunction with chemotherapy may be used in advanced stage to downstage the
tumour prior to surgery or as a primary treatment if there is complete response. The
use of radiotherapy prior to surgery will of course be determined by clinical factors
relating to the extent and site of the disease.
I. Primary Radiotherapy
1)
Very small lesions in unfit patients - Radiotherapy can be limited to the vulva
treating inguinal nodes at recurrence.
2)
Patients with clitoral lesions where surgery would be associated with major
psychosexual sequelae.
3)
Patients with advanced disease where primary surgery is inappropriate - radical
radiotherapy alone or in combination with concurrent chemotherapy may be
considered.
II. Adjuvant Radiotherapy
Factors which will influence the need for radiotherapy in an adjuvant setting are
related to the pathological findings from operative specimens. These include the
surgical margins since the risk of local recurrence increases as the disease-free
margin decreases (>8mm = 0%; 8-4.8mm = 8%; <4.8mm = 54%)3,4 . Adjuvant
radiotherapy for patients with close or involved margins does improve local control.
In patients with positive nodes after radical surgery, adjuvant Radiotherapy
significantly improves survival. A randomised GOG study15 showed 28%
improvement in survival due to decreased incidence of groin recurrence.
Other factors which may influence the decision to give adjuvant radiotherapy include
the presence of an infiltrative growth pattern and lymphovascular space involvement
both of which are associated with an increased risk of local recurrence though not of
nodal metastasis. The majority of recurrences after surgery are locoregional16 and a
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number of clinicopathological variables have been identified which predict local
recurrences and overall3,17.
Adjuvant radiotherapy should be considered:
1)
When two or more nodes are involved or if a single node is completely
replaced by tumour or has extra-capsular spread.
2)
If the excision margin is less than 8mm, but surgical re-excision is an equally
valid approach. Surveillance with surgical salvage at recurrence is also valid in
selected cases.
3)
If one groin is node positive and the other has not been dissected, both groins
and the pelvis should be considered for treatment.
III. Palliative Radiotherapy
In unfit patients with poor performance status and advanced tumours, a palliative
approach is recommended to control symptoms such as pain and bleeding.
IV. Irradiation of Inguinal Nodes
Surgical dissection remains the treatment of choice, although it is not easy to draw
conclusions about the efficacy of inguinal irradiation as primary treatment. A GOG
study comparing groin dissection to groin radiotherapy was closed prematurely as an
excess of groin failure was noted in the irradiated arm 15. There are number of
criticisms of this study. It is clear that the groin nodes would have been inadequately
treated in many patients in this study.
We have to accept from this data that
radiotherapy may be inferior to groin dissection and its use alone should be reserved
for the less fit patients.
9. Chemoradiation
Chemoradiation has never been compared with radiation alone in the pre-operative
setting in vulvar cancer. Several small single arm studies and a recent larger GOG
phase II study have shown high response rates averting the need for exenteration in
most patients
18.
In the GOG study almost half the patients had no visible cancer at
the time of surgery and the vast majority of these had complete pathological
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responses. This has lead to questioning the role of surgery in patients having
complete response. Unlike for anal carcinoma, there is currently insufficient
evidence to advocate chemoradiation as the sole treatment of vulvar cancer. The
morbidity of chemoradiation is the major issue and patients have to be carefully
selected for this aggressive approach. Ideal patients are those with large tumours
where surgery would need to be exenterative.
10. Chemotherapy
Cytotoxic chemotherapy is not regarded as standard treatment in the management
of vulvar cancers but can be used in selected patients with metastatic disease. The
drugs of choice are 5-Fluorouracil and cisplatin, alone or in combination. Single
agent Taxol is considered in patients who progress after first line chemotherapy. The
response rate to chemotherapy is low and the duration of response of the order of 36months.
Suitable patients are those with no co-existing morbidities, and normal organ
function. In view of the age group of the patients with vulvar cancer it is rarely
considered.
11. Treatment at Relapse
Some patients particularly those with local vulvar relapse can be salvaged with
further surgery. Generally patients with nodal and/or distant failure have poor
prognosis and palliative treatments are appropriate. Selected patients may be
considered on an individual basis for more aggressive treatment.
12. Hormone therapy
Hormonal therapy has no significant place in the management of vulvar cancer.
There are no contraindications to the prescription of hormone replacement therapy
in women who have suffered from this disease.
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13. Palliative Care and Nursing care
Palliative care input is appropriate to consider at all stages of the patient’s cancer
journey. Please refer to the separate palliative care guideline for detailed advice.
All women with a diagnosis of a Gynaecological Cancer should be offered the
support of, and have access to a Clinical Nurse Specialist (CNS), in order to
facilitate the woman’s needs throughout the Cancer Journey, including those of her
partner or carer.
The skills of the C.N.S. as a consultant, practitioner and educator can be drawn
upon at all stages throughout their illness, from the pre-diagnosis to the terminal
stage – incorporating the Specialist Palliative Care Services provided in the hospital
and the community setting. Bereavement Support will also be available, if
appropriate.
Important aspects of the role are to provide advice, support, information and to
effectively incorporate appropriate resources. The C.N.S. will be receptive to the
social, physical, psychological, cultural, sexual and spiritual needs of the patient.
The aim of the patient support is to assist with the improvement in the quality of their
lives, allowing them to become more empowered; to help take control and enhance
their self esteem.
The C.N.S. works closely with Surgeons, Oncologists, Radiotherapists, Consultants
in Palliative Medicine and others (Nurses & P.A.M.s).
They will undertake a number of key responsibilities including:

Linking with other professionals who can help the patients throughout the
system

A resource for information and support to the patient carer and other H.C.P.s

Liaison point for other health care professionals in primary and secondary care

Teacher and Educator

Researcher

Standards and Audit Co-ordinator

Co-ordinate Care Services
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14. Follow-up
Standard: Four monthly for years 1 and 2, six monthly to 3 years. Discharge with
open access to CNS in the event of new symptoms or concerns. CNS holistic
assessment is carried out 6 weeks after the completion of primary treatment.
A careful examination of the vulva and examination of the pelvis and inguinal regions
is required.
Patients who have associated VIN or Lichen sclerosus may be reviewed at intervals
in a colposcopy clinic where vulvoscopy can be performed.
Longer term follow-up may be considered in patients treated with radiotherapy.
15. Maintenance of Quality
These guidelines conform to:
Improving Outcomes in Gynaecological Cancers. NHS Executive 1999.
RCOG recommendations on specialists in gynaecological oncology, 1996.
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FIGO Staging Description
FIGO
Description
TNM
1a
Lesion confined to vulva with <1mm invasion,
T1N0M0
superficially invasive vulvar carcinoma
1b
All lesions confined to vulva with diameter <2cm and
no
T1N0M0
clinically suspicious groin nodes
2
All lesions confined to the vulva with a maximum T2N0M0
diameter >2cm and no suspicious groin nodes
3
Lesions extending beyond vulva but without grossly T3N0M0
positive
T3N1M0
groin nodes
T3N2M0
T1N2M0
Lesions of any size confined to the vulva and having T2N2M0
clinically
suspicious groin nodes
4
Lesions with grossly positive groin nodes regardless T1N3M0
of
T2N3M0
the extent of the primary
T3N3M0
T4N3M0
Lesions involving mucosa of rectum, bladder, urethra T4N0M0T4N
or bone
1M0
T4N2M0
All cases of distant metastases
M1A
M1B
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Appendix 1
RADIOTHERAPY DETAILS
Radical Radiotherapy

Radiotherapy dose of 60 Gy or equivalent.

45 Gy in 25 fractions over 5 weeks followed by phase II to gross disease, to
equivalent dose of 60 Gy.

Preoperative dose of 45 Gy in 25 fractions over 5 weeks with concurrent
chemotherapy in selected cases.
Concurrent Chemoradiation

45 Gy in 25 fractions over 5 weeks with concurrent 5-fluorouracil infusion plus
cisplatin on weeks 1 and 4, or weekly cisplatin for 5 weeks. Followed by small
volume boost taking the dose to 60 Gy.

50.4 Gy in 28 fractions with concurrent 5-FU in 2 phases followed by boost (as
above) to a total dose equivalent to 60 Gy.

A split course is recommended in patients with severe acute skin reactions.
Palliative Radiotherapy dose schedules
30 Gy in 10 fractions over 2 weeks
20 Gy in 5 fractions over 1 week
8 Gy single fractions
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References
1
RCOG publications. (2006) Clinical Recommendations for the Management of
Vulvar Cancer. July 1999.
2
Holmsley, HD, Bundy, BN, Sedlis, A et al (1991). Assessment of current
International Federation of Gynecology and Obstetrics staging of vulvar carcinoma
relative to prognostic factors for survival (a Gynaecologic oncology group study). Am
J Obstet Gynecol 164, (4), 997-1004.
3
Heaps, JM, Yao SF, Montz FJ, Hacker NF, Bereck JS. (1990). Surgical-
pathological variables predictive of local recurrence in squamous cell carcinoma of
the vulva. Gynecol Oncol 38, 309-314.
4
Hacker NF. And Van der Velden J. (1993) Conservative management of early
vulvar cancer. Cancer71, 1673 - 1677.
5
Herod JJO
6
Partridge EE, Murad T, Shingleton HM. Et al. (1980) Verrucous lesions of the
female genitalia 2. Verrucous carcinoma. Am J Obstet Gynecol 137, 412-418.
7
Helm CW, Shingleton HM. et al. (1992) The management of squamous carcinaom
of the vulva. Curent Obstet Gynecol 2, 31-37.
8
Davison T, Kissin M and Westbury C. (1987) Vulvo-vaginal melanoma - should
radical surgery be abandoned? Br J Obstet Gynaecol. 94, 473-476.
9
Hacker NF, Leuchter RS, Bereck, JS Castaldo TW and Lagasse LD. (1981).
Radical vulvectomy and bilateral inguinal lymphadenectomy through separate groin
incisions. Obstet Gynecol. 58, 574-579.
10
Stehman FB, Bundy BN, Dvoretsky PM and Creasman WT (1992). Early stage 1
carcinoma of the vulva treated with superficial inguinal lymphadenectomy and
modified rasdical hemivulvectomy. A prospective study of the GOG. Obstet Gybecol.
79, 490-497.
11
Sentinel Node Dissection Is Safe in the Treatment of Early-Stage Vulvar Cancer.
A. Van der Zee et al. Journal of Clinical Oncology, Vol 26, No 6 (February 20), 2008:
pp. 884-889.
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12
The role of high resolution ultrasound with guided cytology of groin lymph nodes in
the management of squamous cell carcinoma of the vulva: a pilot study. Moskovic E.
et al. BJOG 1999 Aug;106(8):863-7.
13
Hacker NF, Berek JS, Juillard JF and lagasse LD (1984). Pre-operative
radiotherpy for locally advanced vulvar cancer. Cancer 54, 2056-2061.
14
Rotmensch J, Rubin SJ, Sutton HG, Javaheri G, Halpern HJ, Schwarz JL, Stewart
M, Weichselbaum RR and Herbst AL. (1990) Pre-operative radiotherapy followed by
radical
vulvevctomy
with
inguinal
lymphadencetomy
for
advancedf
vulvar
carcinomas. Gynecol Oncol 36, 181-184.
15
Homsley HD, Bundy LN, Sedlis A, Adcock L. (1986). Radiation therapy versus
pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet
Gynecol 68: 733-740.
16
Bryson SC, Dembo AJ, Colgan TJ et al (1991) Invasive squamous cell carcinoma
of the vulva defining low and high risk groups for recurrence. Int J Gynecol. Cancer,
1, 25-31
17
Hopkins MP, Reid GC, Vettrano I et al (1991) Squamous cell carcinoma of the
vulva prognostic factors influencing survival. Gynecol. Oncol, 43, 113-17
18
Moore D, Thomas G, Montana G. (1998). Preoperative chemoradiation for
advanced vulvar cancer: a phase II study of the Gynaecologic Oncology group. Int
J Radiat Oncol Biol Phys 42: 79-85
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