Professional Documents
Culture Documents
Gynaecological Oncologist
Department of Gynaecology, Coombe Women’s Hospital, Dolphin’s Barn Street, Dublin 8, Ireland
Vulval cancer has an incidence of 1 –2/100 000. Approximately one-third of patients develop
recurrent disease usually within the first 2 years following primary treatment. Isolated vulval
recurrences account for up to 50% of all cases and these recurrences are often amenable to
curative surgery with radical wide local excision. Reconstruction and skin closure for larger
surgical defects necessitate skin flaps. Radical exenterative procedures are considered when the
recurrence involves the urethra, bladder, vagina and/or the anorectal canal. Chemoradiation
therapy may be used pre-operatively or to palliate the disease. Disease recurrence in the groin is
difficult to treat and is associated with very poor survival rates. Surgical effort to debulk large-
volume groin disease is often unsuccessful and chemoradiation therapy is the cornerstone of
treatment. The management of retroperitoneal and distant disease recurrence is generally based
on symptom control as radiation therapy and chemotherapy have limited success. Palliative
medicine should be integrated early in the management plan both in patients with incurable
recurrent disease and in those undergoing potentially curative treatments.
appropriate investigation and assessment the aim should be determined. Poor survival
rates after recurrence of vulval cancer are associated with nodal/distant recurrence,
short time interval to recurrence and increasing tumour grade.6 – 10 Many dilemmas
arise for both the gynaecological oncologist and the patient. In this chapter we address
the issues of treatment of recurrent disease as well as critical analysis of the treatment
modalities. We also discuss the management of specific symptoms of recurrent disease
which are all too often more distressing to patients than the disease itself.
Patterns of recurrence
Squamous vulval cancer recurs after primary treatment in 12– 37% of patients6 – 13
(Table 1). The size of the lesion, close margins of resection (, 1 cm) and lymph node
status at primary surgery are the main predictors of recurrence.6 – 13 Preti et al14
reported that lymphvascular space invasion was also an important factor. Heaps et al6
reported 21 (16%) vulval recurrences out of a total 135 patients with squamous vulval
cancer. Ninety-one patients with a tumour-free margin of $ 8 mm on tissue section had
no local vulval recurrences. Fifty percent of those with a tumour-free margin of , 8 mm
had a local recurrence. Recurrence is very unlikely when the deep margin has a tumour
clearance of more than 10 mm.6 Thus, allowing for tissue shrinkage during laboratory
fixation of the tumour, surgical lateral and deep tumour-free margins of less than 10 mm
are associated with a greater risk of local recurrence. This risk is independent of the type
of radical surgery performed. The risk of local recurrence is not increased following
radical local excision compared to radical vulvectomy.15 The pattern of invasion in the
primary tumour influences metastasis and local recurrence rates. A confluent or pushing
pattern has a lower risk of recurrence than a stellate or spray pattern.6 The presence
of multiple disease sites, multiple lymph node involvement and the presence of
extracapsular inguinofemoral lymph nodal disease are associated with the highest risk
of recurrence.8,16 – 18 Other authors have expressed concern that a 1 cm margin may not
be adequate, is associated with an increased incidence of local recurrence and indicated
that a 2 cm margin should be the goal of surgical management in primary disease.19
Fifty percent to 70% of recurrences have a local component on the vulva/perineum.6,7
Isolated vulval/perineal recurrences are more common if the inguinofemoral lymph
nodes are negative at primary surgery. The multicentre study of Maggino et al reported
Podratz et al (1982)8 68 22 19 17
Prempree and Amornmarn (1984)27 86 38 5 N/A
Cavanagh and Shepherd (1982)39 53 11 5 37
Piura et al (1993)7 82 11 31 8
Maggino et al (2000)9,a 53 19 6 8
a
Data for isolated recurrences. Multiple site recurrences occurred in 14%.
patterns of recurrence in 187 patients: 53% had isolated vulvoperineal recurrence, 19%
inguinal, 6% pelvic, 8% distant and 14% had multiple site recurrences. Isolated vulval/
perineal recurrences were more likely to occur in patients with negative inguinal lymph
nodes (57%) than in patients with inguinal node metastases (27%). Overall, 52% patients
with metastasis to inguinal lymph nodes developed disease recurrence compared to 31%
without nodal involvement.9 Other studies demonstrate the dominance of local
vulvoperineal recurrences but do not give the rates of isolated local recurrences. Piura
et al7 and Podratz et al8 report overall recurrence rates of 19% (of 376 patients) and 26%
(of 224 patients) but their series contained only 33 and 40% stage I patients, respectively.
Podratz et al reported that 68% patients had a local vulval recurrence, 22% recurred in
the groin, 19% in the pelvis and 17% had distant recurrence. Piura et al quote an even
higher rate of local vulval recurrence (82%),with 11% recurring in the groin, 31% in the
pelvis and 8% distant disease. Combining the largest studies, the average recurrence
rates are 57% vulvoperineal, 22% groin, 14% pelvic and 23% distant (Table 2).
Adjuvant radiation treatment has been proven in primary treatment for patients with
positive or ‘close’ margins. Thomas et al20 reported no ‘in field’ recurrences in nine
patients treated with adjuvant chemoradiation. Faul et al21 studied 62 patients with
positive or ‘close’ surgical margins and compared 31 who received adjuvant radiation
with 31 observed patients. There were significantly less local recurrences in the
irradiated group (16%) compared to the observed group (58%) and the positive margin
observed group had a significantly poorer actuarial 5-year survival than the irradiated
group.
The risk of groin node metastases in primary vulval carcinoma is related to the depth
and size of tumour and to the presence of vascular space invasion. Pelvic node
metastasis is very rare in the absence of inguinofemoral nodal disease. Macroscopic
nodal disease, multinodal disease, extracapsular spread and any metastases to the pelvic
nodes predict nodal recurrence. Maggino et al9 reported isolated inguinal recurrence
rates increasing from 13% when the inguinal nodes were initially negative to 26% when
less than three nodes were involved to 31% when more than three nodes were positive.
Preti et al14 reported 33% inguinal recurrence rate in their series. Five of eleven patients
had an isolated groin recurrence and six had combined groin and vulval recurrences.
Pelvic nodal disease at primary diagnosis correlates with the extent of inguinal nodal
involvement. Pelvic node metastasis, in turn, carries a high risk of distant metastasis22.
Timing of recurrence
Up to 80% of recurrences occur within the first 2 years after primary treatment. Close
follow-up of patients treated for vulval cancer is recommended to detect recurrences
666 J. Coulter and N. Gleeson
Sites of recurrence
Two-thirds of recurrences have an external component on the skin of the vulva and/or
perineum.6,7 Recurrence in the inguinal and/or pelvic lymph nodes may occur in isolation
or in association with vulval or distant metastasis. Retrograde lymphatic metastasis may
result in widespread cutaneous involvement of the lower trunk and upper thighs (Figure
1). Some authors have subdivided the recurrence on the basis of the proximity of the
recurrence to the original surgery and have described skin-bridge recurrences
separately.13 Histological confirmation is required. Outpatient punch biopsy of skin
lesions and fine-needle aspiration of lymph nodes provide adequate histological or
cytological material for diagnosis. The extent of disease recurrence is determined prior
to the planning of treatment. Physical examination reveals superficial disease on the skin,
inguinal or pelvic nodes or distant metastases, and pelvic examination may locate disease
in the urethra, vagina, anorectum or pelvic sidewalls. The presence of extravulval and
extrapelvic disease alters management strategies significantly. Diagnostic imaging assists
in the ‘re-staging’. CT or MRI scans are used to locate metastases within the pelvis and
abdomen and to assess the retroperitoneum. Positron emission tomography (PET) scans
are increasingly being employed for the detection of recurrent disease. A recent study by
Cohn et al23 reported a sensitivity of 80% specificity of 90% and positive predictive value
of 80% for PET detection of groin node metastases in primary vulval cancer. Most of the
current data looking at the role of PET scanning are in recurrent cervical cancer with
sensitivities in the order of 80 –90% and specificities approaching 100%. Chest X-ray, CT
scan and PET scan may detect pulmonary metastases.
The management of patients with recurrent vulval cancer depends on the patient and
disease variables. The site of recurrence may be local at the vulva/perineum or may
involve the adjacent organs, namely, the urethra, bladder, vagina or anorectum.
Recurrence may be at one or both of the groins or in the pelvic lymph nodes. Distant
metastases to the lungs or skeleton may be diagnosed. The type and extent of primary
treatment, the previous use of adjuvant therapy, the current medical status and wishes
of the patient all play an important role in the decision for further treatment. Vulval
cancer is rare and recurrent disease even less common. The related literature consists
mainly of small retrospective single-institution reports. Prospective randomized trials
are not available to determine the optimal treatment of recurrent disease. However,
there is widespread consensus regarding the principles of management of disease
recurrence, and novel strategies have ensued from the studies of squamous cancer at
other sites. The disease-free interval (DFI) or time to relapse has a major impact on
prognosis, with fewer patients salvaged as the DFI decreases. Extrapolating from other
cancers a useful guide is poorer survival if the DFI is less that 2 years.
Recurrence: management dilemmas 667
Figure 1. (A) Recurrent vulval cancer on the mons pubis and left groin nodes. Note the multiple cutaneous
metastatic deposits at the vulva and upper thigh. (B) A view from above in the same patient.
668 J. Coulter and N. Gleeson
In the absence of obvious metastatic disease the treatment aim is curative. Most lesions
are amenable to radical surgical resection and this is generally held to be the procedure
of choice. The surgical excision of the recurrent lesion must include an adequate
tumour-free margin but we do not know whether the data from primary treatment can
be extrapolated to repeat radical excisions. Salom and Penalver24 recommend a 2 cm
tumour-free margin when excising recurrent disease. A generous tumour-free margin
may necessitate a very large diameter of tissue excision, depending on the size of the
recurrence. Scarring from previous surgery results in reduced tissue volume and
flexibility. The skin is typically scarred directly to the deep fascia. The deep margin of the
excision of recurrent disease must also go to the deep urogenital fascia. Primary skin
closure may be achievable only in small-volume recurrent disease. Repeat radical
excision in patients who have had previous complete radical vulvectomy or radiotherapy
may require a flap to cover the defect and/or reconstruct the vulva and lower vagina.
Smaller vulval defects can be satisfactorily closed with a local full-thickness skin flap;
for example a Z-plasty or rhomboid flap may suffice to close the defect. Barnhill et al25
have eloquently described the technique for rhomboid flaps. The medial incision of the
‘V’ approximates the length of the defect to be closed while the lateral limb of the ‘V’
approximates the width of the defect or part of the width if bilateral rhomboid flaps are
to be used. When the defect is larger or reconstruction of the lower vagina is necessary
myocutaneous flaps are employed. Myocutaneous flaps have the advantage that the size
and shape can be individualized to suit the defect and the flap brings a new blood supply
to an area that may have a compromised blood supply following the surgery and/or
radiation.
Various myocutaneous grafts have been described for the purpose of closing vulval
defects. These include gracilis, rectus abdominis, tensor fascia lata and gluteus maximus
flaps. The choice of myocutaneous graft to be used depends on the anatomy of the
defect. The gynaecological oncologist often consults with the plastic/reconstructive
surgeons pre-operatively to decide on the procedure required. The patient is advised
on the need for a donor site prior to the procedure—these donor sites can be more
painful than the vulval recipient site post-operatively. Skin, subcutaneous fat, fascia and
underlying muscle based on a vascular pedicle are dissected and transposed in to cover
the defect in the vulva or vagina, and closure without tension is achieved.26 The vascular
pedicles are the obturator artery for the gracilis flap, inferior epigastric for the rectus
abdominis flap, lateral circumflex femoral artery for the tensor fascia lata flap and
inferior gluteal artery for the gluteus maximus flap (Figure 2).
Some patients with recurrence of vulval cancer will not have had an inguinal
lymphadenectomy performed –at the time of previous surgery due either to missed
primary diagnosis, diagnosis of microinvasive disease, or to inadequate primary
treatment. In the presence of local recurrence a unilateral or bilateral inguinofemoral
lymphadenectomy should be performed depending on the location of the recurrence.
Post-operative radiation ^ chemotherapy should be employed if the margins of
excision are positive or if metastatic disease is detected in the inguinal nodes, assuming
no prior radiation treatment had been employed.24
(continued)
Figure 2
Recurrence: management dilemmas 671
(continued)
Figure 2
672 J. Coulter and N. Gleeson
Surgery or chemo/radiatherapy?
Figure 3. Radionecrosis of skin over the symphysis pubis in a patient with recurrent vulval cancer following
radical vulvectomy undergoing external beam radiotherapy.
chemotherapy is considered for bulky local disease when the recurrence involves
urethra, bladder, vagina or anorectum in women who have not previously had radiation
treatment of the vulva (Figure 4). This may spare the patient from exenterative surgery,
but a defunctioning colostomy may be necessary prior to radiotherapy if the recurrence
is close to the anorectal canal. Thomas et al20 published a retrospective study of
recurrent vulval cancer treated with chemoradiation followed by surgery and reported
a 46% 2-year survival rate. Eight of the 15 patients with recurrent disease had a
complete response to treatment. Russell et al38 reported four complete and three
partial response rates in seven patients with recurrent disease treated by
chemoradiation. Two patients survived to 2 years. Overall 5-year survival rates for
patients with recurrent vulval cancer are 25– 35%. However, 5-year survival rates after
radical wide local excision for isolated vulval/perineal recurrences range from 50 to
70% and justify the sometimes extensive surgical/radiotherapeutic modalities of
treatment.7,10 – 12,14
Ultraradical surgery
The prognosis for groin recurrence of vulval cancer is very poor, with 5-year survival
rates of 0– 8%.5,11,16,17 Hopkins et al11 reported no disease-free survivors in a series of
10 patients with groin recurrence. Groin recurrence appears to predict survival. Six
patients in Hopkins’ study received adjuvant radiation to the groin after excision of the
lymph nodes without benefit. Simonsen12 reported only one disease-free survivor out
of 12 patients with groin recurrence. Salvage is negligible if pelvic lymph nodes are
involved.
Figure 5. Extensive right groin and upper thigh recurrence in a patient with previous groin irradiation.
a case report. The vascular graft occluded 21 months after surgery but the patient was
clinically free of disease 4 years following the reconstructive surgery. Deppe et al48
had previously reported successful limb salvage with bypass graft in a patient who
suffered femoral artery rupture in the presence of recurrent vulval cancer. More
recently, Sevin et al49 described a case of radical although palliative limb-sparing
surgery for groin node recurrence. Radical surgical effort should be considered as an
alternative to radiation in otherwise healthy patients. These cases are very rare and
no successful surgical or combined treatment modality has yet been described. With
the increased use of the triple-incision rather than radical en bloc dissection, isolated
skin bridge metastases have been described in patients with and without groin node
metastases.13,50,51 These may represent recurrences or late presentation of a skin
metastases after initial surgical treatment. If the skin bridge is an isolated site of
disease radical local excision is effective treatment.
Pelvic recurrence is typically sidewall nodal disease and usually concomitant with groin
node recurrence. Surgical excision is not usually feasible and chemotherapy and
radiotherapy are the mainstays of treatment. Pelvic recurrence is often associated with
distant metastatic disease and survival is rare.52 In the presence of distant disease
Recurrence: management dilemmas 677
the aim of local therapy is to achieve symptom control. Patients with para-aortic nodal
recurrence often complain of back pain, lower limb pain and dysaesthesia and/or
gastrointestinal symptoms related to disordered gut motility. Appropriate analgesia is
prescribed. Pain can sometimes be palliated by the use of a small field of radiation to the
area of tumour recurrence. Pro-kinetic agents may help restore gut function. A
gastrostomy tube should be considered if long-term nasogastric suctioning is
required.53 The lung is the most frequent site of distant recurrence.7 Patients’
symptoms in this setting are more often related to other synchronous metastatic sites
such as vulva, groin, retroperitoneal nodes or axial skeleton. Palliative relief of bone
pain with radiation is achievable for patients with symptomatic skeletal metastases.
Therapeutic options include chemotherapy, radiotherapy and, most importantly,
palliative care. Chemotherapy can be employed for patients with advanced locoregional
recurrence not amenable to surgery or radiation and for those with distant disease.
Active agents include the platinum drugs, bleomycin, methotrexate, mitomycin C and 5-
fluorouracil. Wagenaar et al54 reported a 56% response rate in 25 patients (two
complete and 12 partial responses) using bleomycin, methotrexate and CCNU
(Lomustine). However, the regimen was associated with a major haematological
toxicity profile. The median progression-free survival was 4.8 months and median
survival 7.8 months. Response rates to chemotherapy are usually poor and the duration
of response usually short. There is little evidence available that combination
chemotherapy has any advantage over single-agent treatment. The use of a single-
agent platinum drug may be the most appropriate for patients considered too unwell to
tolerate treatment. 5-Fluorouracil is a reasonable alternative for older or less medically
fit women and can now be given as an oral preparation.
PALLIATIVE CARE
Practice point
† vulval cancer recurs in 12– 37% of patients
† 80% of recurrences occur within 2 years of primary treatment
† isolated vulval recurrences are more likely if lymph nodes are free of disease at
primary surgery
† in the absence of metastasis wide local excision is the mainstay of treatment of
vulval recurrences
SUMMARY
The low incidence of vulval cancer makes management of its recurrence a rare event
for the gynaecological oncologist. With increased incidence of the disease in
immunodeficient patients—whose immunodeficiency may arise from both acquired
infections and survival to adulthood of females with congenital immune deficient
Recurrence: management dilemmas 679
states—we can expect this challenge to expand numerically and to include more
younger women in the future. Newer treatment modalities, such as immunotherapy
(BCG and recombinant human interleukin-2), are currently being investigated with
some success and may have a role in the future treatment of these women. At present,
the principles of management of recurrent vulval cancer include: the precise delineation
of recurrence site(s), the optimal use of surgery and/or chemoradiation to achieve cure
and/or local control, and the correct identification of patients who are not curable but
who may benefit from palliative surgery, radiation or chemotherapy. Treatment must be
tailored to the individual patient’s needs and expectations. Many patients with
recurrent vulval cancer die of their disease. The palliative care team is invited to
participate early in the patient’s clinical course to maximize her quality of life.
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