Vulvar cancer has been staged by the International Federation of Gynaecology and Obstetrics (FIGO) since 1969, and the original staging system was based on clinical findings only. This system provided a very good spread of prognostic groupings. Because vulvar cancer is virtually always treated surgically, the status of the lymph nodes is the most important prognostic factor and this can only be determined with certainty by histological examination of resected lymph nodes, FIGO introduced a surgical staging system in 1988. This was modified in 1994 to include a category of microinvasive vulvar cancer (stage IA), because such patients have virtually no risk of lymph node metastases. This system did not give a reasonably even spread of prognostic groupings. In addition, patients with stage III disease were shown to be a heterogeneous group prognostically, and the number of positive nodes and the morphology of those nodes were not taken into account. A new surgical staging system for vulvar cancer was introduced by FIGO in 2009. Initial retrospective analyses have suggested that this new staging system has overcome the major deficiencies in the 1994 system.
Staging is used to describe the extent of an individual’s cancer. Four basic stages are described, and these are assigned by dividing the extent of the disease into four categories, based on increasingly poor prognostic features. Ideally, the 5-year survival for the four stages should be reasonably evenly distributed between 0% and 100%.
For an individual patient with vulvar cancer, an accurate knowledge of the extent of her disease is critical for optimal management, and for determining the prognosis. Staging is also important beyond the individual patient, because it allows patients to be placed in reasonably homogeneous groups, so that results can be compared between treatment centres internationally. It also facilitates entry of reasonably homogeneous groups of patients on to clinical trials.
The most widely used staging system for vulvar cancer is the one defined by the International Federation of Gynaecology and Obstetrics (FIGO) , but vulvar cancer may also be staged according to the TNM classification, which is used by both the American Joint Commission on Cancer (AJCC) and the Union for International Cancer Control (UICC) . There was close collaboration between FIGO, AJCC and UICC in developing the 2009 staging system for vulvar cancer.
Earlier FIGO staging systems for vulvar cancer
The first FIGO staging system for vulvar cancer was introduced in 1969. The system was based on a clinical evaluation of the primary tumour and regional lymph nodes, and a limited search for distant metastases . Basically, patients with stage I disease had a primary tumour confined to the vulva ≤2 cm in diameter, with no suspicious groin nodes; patients with stage II disease had a tumour confined to the vulva >2 cm in diameter with no suspicious groin nodes; patients with stage III disease had a tumour that had spread to the urethra, distal vagina or anus, or clinically suspicious groin nodes; and patients with stage IV disease had infiltration of the bladder, rectum or proximal urethral mucosa, fixation to bone or distant metastases.
This clinical staging was easy to apply, and it gave a reasonable distribution of prognostic groups, the 5-year survivals being 90.4%, 77.1%, 51.3% and 18% for patients with stages I, II, III and IV, respectively . This prognostic distribution reflected the fact that the status of the lymph nodes is the single most important prognostic factor in vulvar cancer , and the incidence of lymph node metastases increased with each stage, with 10.7% for patients with stage I disease, 26.2% for stage II, 64.2% for stage III and 88.9% for stage IV .
Both microscopic and macroscopic metastases may be present in lymph nodes that are not palpable, and suspicious nodes may be enlarged because of inflammatory changes only. Clinical evaluation of lymph nodes is therefore inaccurate in approximately 20–30% of cases . Because vulvar cancer is virtually always treated surgically and the true status of the lymph nodes can only be determined histologically, FIGO introduced a surgical staging system for the disease in 1988.
The 1988 FIGO surgical staging system was modified in 1994, with the subdivision of stage I into IA and IB. Stage IA was a lesion up to 2 cm in diameter, with stromal invasion not greater than 1 mm. Such patients have virtually no risk of lymph node metastases , so they can be treated by radical local excision alone. The 1994 FIGO staging is shown in Table 1 .
| FIGO stage | Clinical/pathologic findings |
|---|---|
| C | |
| Stage I | Tumour ≤2 cm in greatest diameter, confined to the vulva or perineum; nodes are negative |
| IA | As above with stromal invasion ≤1.0 mm a |
| IB | As above with stromal invasion >1 mm |
| Stage II | Tumour confined to the vulva and/or perineum, >2 cm in greatest dimension, nodes are negative |
| Stage III | Tumour of any size with: |
| 1. Adjacent spread to the lower urethra and/or the | |
| vagina and/or the anus | |
| 2. Unilateral regional lymph node metastasis | |
| Stage IVA | Tumour invades any of the following: Upper urethra, |
| bladder mucosa, rectal mucosa, pelvic bone or | |
| bilateral regional node metastasis | |
| Stage IVB | Any distant metastasis including pelvic lymph nodes |
a The depth of invasion is defined as the measurement of the tumour from the epithelial–stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion.
In 1991, the Gynecological Oncology Group (GOG) reported a retrospective analysis of 588 patients with vulvar cancer available from their database . This analysis highlighted a number of problems with the new surgical staging system.
The first problem was that the new system did not give a reasonably even spread of prognostic groupings. The GOG study demonstrated that when the tumour had negative lymph nodes, even primary lesions with up to 8-cm diameter had an excellent prognosis . An analysis of 121 cases of stages I and II squamous cell carcinoma of the vulva managed at the Royal Hospital for Women in Sydney from 1987 to 2005 showed no difference in recurrence rates, time to recurrence or survival between patients with 1988 FIGO stages I or II disease. The 5-year actuarial survival for patients with stage I disease was 97%, compared to 95% for patients with stage II ( p = 0.83) .
A second problem was that patients with stage III disease were a heterogeneous group prognostically, with survivals ranging from 100% to 34% . For example, the GOG study reported six patients with tumours ≤2 cm in diameter with negative nodes, but with involvement of the distal vagina and/or urethra. Their survival was 100%. There were 47 patients who had a tumour <2 cm in diameter with one positive node, and their survival was 95%. On the other hand, 28 patients had a tumour >8 cm in diameter with two positive nodes, and their survival was only 34%, yet all of these patients were officially classified as having FIGO stage III disease . In addition, Rouzier et al. reported a cohort of 895 patients with FIGO stage III vulvar cancer who had been registered with the Surveillance, Epidemiology, and End Results (SEER) database from 1988 through 2004. The 5-year overall survival (OS) for patients with regional metastatic nodal disease (39%) was significantly worse than that of patients with locally advanced tumours but negative nodes (62%; p < 0.0001) .
A third problem with the 1988 FIGO staging was that the number of positive nodes, and the morphology of those nodes, was not taken into account. The GOG study reported a 5-year survival of 90.9% for 385 patients with negative nodes, 75.2% for 125 patients with one to two positive nodes, 36.1% for 40 patients with three to four positive nodes, 24.0% for 19 patients with five to six positive nodes and 0% for 16 patients with seven or more positive nodes .
A recent study from Brazil retrospectively analysed 234 patients who underwent inguinal lymphadenectomy for vulvar squamous cell carcinoma between January 1980 and February 2010. Lymph node metastases were present in 107 patients (45.7%). Patients with negative nodes had a disease-specific 5-year survival of 78.2%, compared to 48.7% for patients with one to two positive nodes ( p = 0.004) and 30% if there were three or more positive nodes ( p = 0.025) .
The significance of the morphology of the positive nodes was not appreciated until 1992, when Origoni et al. demonstrated survivals of 90.0%, 41.6% and 20.6% for nodal metastases <5, 5–15 and >15 mm in diameter, respectively . They also demonstrated that patients whose lymph node metastases had extracapsular spread had a much worse prognosis (25%) than patients in whom the metastatic disease was confined to the node (85.7%; p = 0.001). Other studies have subsequently confirmed these findings . The percentage of the lymph node replaced by tumour has also been shown to be significant in multivariate analysis .
The fourth problem was that the number of positive nodes is the critical prognostic factor, not the bilaterality of the positive nodes, yet the 1988 FIGO staging classified patients with unilateral regional lymph node metastases as having stage III disease, and patients with bilateral regional lymph node metastases as having stage IVA disease. Although the majority of reported studies have indicated that bilaterality was not an independent prognostic factor , others have suggested that it was . Papers suggesting that bilaterality was an independent risk factor included patients with only one positive node in the analysis. This is clearly invalid, because such patients are not at risk of having bilaterally positive nodes.
Just prior to the publication of the 2009 FIGO staging, a Dutch group reported 134 patients with stage III/IVA vulvar cancer. They demonstrated that the presence of bilateral lymph node metastases was not a significant prognostic factor if the correction was made for the number of positive nodes .
New 2009 FIGO staging for vulvar cancer
In view of the above considerations, the 1994 FIGO staging was modified in 2009 ( Table 2 ). Stage IA was not changed, but the former stages IB and II were combined to create a new stage IB. This is now a tumour of any size greater than stage IA, confined to the vulva and with negative lymph nodes. All of these patients should have a good prognosis. A tumour of 1-cm diameter with 2 mm of stromal invasion would be stage IB, as would a tumour 3 cm in diameter with a maximum depth of invasion of 1 mm.
| Stage I | Tumour confined to the vulva |
| IA | Lesions ≤2 cm in size, confined to the vulva or perineum and with stromal invasion ≤1.0 mm, a no nodal metastasis |
| IB | Lesions >2 cm in size or with stromal invasion >1.0 mm, a confined to the vulva or perineum, with negative nodes |
| Stage II | Tumour of any size with extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with negative nodes |
| Stage III | Tumour of any size with or without extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with positive inguino-femoral lymph nodes |
| IIIA | (i) With one lymph node macrometastasis (≥5 mm), or |
| (ii) One to two lymph node micrometastasis(es) (<5 mm) | |
| IIIB | (i) With two or more lymph node macrometastases (≥5 mm) or |
| (ii) Three or more lymph node micrometastases (<5 mm) | |
| IIIC | With positive nodes with extracapsular spread |
| Stage IV | Tumour invades other regional (2/3 upper urethra, 2/3 upper vagina), or distant structures |
| IVA | Tumour invades any of the following: |
| (i) upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa or fixed to pelvic bone, or | |
| (ii) fixed or ulcerated inguino-femoral lymph nodes | |
| IVB | Any distant metastasis including pelvic lymph nodes |
a The depth of invasion is defined as the measurement of the tumour from the epithelial–stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion.
The former stage III has been divided into new stages II and III, to overcome the heterogeneity of the former stage III. Patients with spread to the lower third of the urethra and/or the lower third of the vagina or anus with negative nodes form a fairly homogeneous group prognostically, and they are classified as stage II.
All stage III patients now have positive nodes, with subdivision into stages IIIA, B and C to take into account the prognostic implications of the morphology of the nodes. Bilateral involvement is no longer included in the staging, but only the number of the positive nodes, the diameter of the metastatic foci and the presence or absence of extracapsular spread.
Stages IVA and B remain essentially unchanged, except that patients with bilaterally positive groin nodes are no longer classified as having stage IVA disease. They would be classified as having at least stage IIIA (ii).
The 2009 FIGO vulvar cancer staging has been shown to be an improvement on the 1988 staging in several retrospective institutional reviews.
The first report was from Nijimegen in the Netherlands, where 269 patients with vulvar squamous cell carcinoma treated from 1988 to 2009 were retrospectively staged according to the old and revised FIGO staging systems . As a result of the restaging, 113 patients (42.4%) were reclassified into a lower stage. No patients were upstaged. The greatest change was in patients with tumours confined to the vulva with negative lymph nodes – all 81 patients (30.1%) with old stage II disease were downstaged to IB. The 76 patients (28.3%) with old heterogeneous stage III disease were reclassified into stage II (7 patients, 9.2%), stage IIIA (40 patients, 52.6%), stage IIIB (eight patients, 10.5%) and stage IIIC (21 patients, 27.6%). The 31 patients (11.5%) with old stage IVA disease were reclassified into stage IIIA (four patients, 12.9%), stage IIIB (10 patients, 32.3%), stage IIIC (11 patients, 35.5%) and stage IVA (six patients, 19.3%).
This study confirmed that, in patients with negative nodes, the tumour diameter was not predictive of OS ( p = 0.475) or disease-specific survival ( p = 0.915). There was also a decreasing OS for patients with stages IIIA, IIIB and IIIC disease ( p = 0.005). The 5-year disease-specific survival was 77% for patients with one positive node, 62% for two or three positive nodes and 28% for four or more positive nodes. Patients with intranodal lymph node metastases ( n = 54) had a 5-year disease-specific survival of 72% compared to 45% for 32 patients with extranodal spread ( p = 0.004). There was no significance to the presence or absence of bilaterally positive nodes when the individual stages of disease were taken into account .
A retrospective review of 468 patients undergoing surgery for vulvar cancer from the Mayo Clinic and the Medical University, Gdansk, Poland, reported that the new staging system downstaged 31% of patients ( n = 155), with only one patient upstaged from III to IVA because of grossly ulcerated lymph nodes . The new staging failed to separate stages IB and II in terms of 10-year cause-specific survival ( p = 0.52), but the authors felt that the complexity and morbidity of treating tumours involving the urethra, vagina and anus were much higher, and would justify the assignment of such tumours to a higher stage. Only 31 patients had stage II disease, limiting the power to find a statistically significant survival difference. Similarly, they were unable to show a statistically significant difference between the substages of stage III, probably because of small numbers of cases in each substage, but they did find a strong trend toward worse survival in patients with extracapsular spread. Their study supported the omission of bilateral lymph node involvement from the new staging system.
The group at the Queensland Centre for Gynaecological Cancer retrospectively reviewed 394 patients treated in Brisbane from 1988 until 2009 . Seventy-two patients were downstaged (18.3%) and five upstaged (1.3%), because of ulcerated groin nodes. Their data confirmed the wisdom of combining the old stages IB and II. OS and relapse-free survival (RFS) for substages IIIA and IIIB were similar and ranged between 50% and 60% at 5 years, but the number of patients in each substage was relatively small. Patients with stage IIIC disease had an RFS of only 18% at 5 years. They concluded that the FIGO 2009 staging system successfully addressed some of the concerns of the 1988 system, and they noted that it especially identified high-risk patients within the heterogeneous group of lymph-node-positive patients.
From the three major retrospective reviews above, it is apparent that the new staging system has seen a major downstaging of about 30% of patients ( Table 3 ). This has mainly involved old patients with stage II disease being downstaged to stage IB. This has generally been considered appropriate, although Tabbaa et al. suggested that tumours >4 cm in diameter had a less favourable prognosis. Less than 1% of patients were upstaged by the new system ( Table 3 ).
| Author | Number | Downstaged | Upstaged |
|---|---|---|---|
| van der Steen et al. 2010 | 269 | 113 (42%) | 0 |
| Tabbaa et al. 2012 | 468 | 155 (31%) | 1 (0.2%) |
| Tan et al. 2012 | 394 | 72 (18.3%) | 5 (1.3%) |
| 1131 | 340 (30.1%) | 6 (0.5%) |
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