Vulval cancer comprises 4% of female gynecological malignancies, with squamous cell type representing 90% of the cases.1 Human papillomavirus is thought to be a causative agent among other risk factors including vulva dystrophy, cigarette smoking, vulva or cervical dysplasia, history of cervical carcinoma, immunodeficiency, and northern European ancestry.2 Its treatment involves a combination of radical local excision and inguinofemoral lymphadenectomy with or without postoperative radiotherapy. Recent studies have shown that use of sentinel lymph node dissection may be a less morbid alternative to full groin node dissection.3
In 1988, the 1970 International Federation of Gynecology and Obstetrics (FIGO) vulva cancer staging was changed from clinical to surgical staging because clinical assessment of lymph node involvement is unreliable, and lymph node metastasis remains the most important prognostic factor.4–6 However, it has become evident that the 1988 staging system failed in 3 important areas7: (1) It did not give a good spread of prognostic groupings, as it is generally accepted that stages I and II had no difference in survival. (2) Stage III represented a group of patients with varying prognosis, with a large survival range. (3) Number and morphology of positive nodes were not taken into account; and it has become increasingly evident that morphology of positive nodes is a significant prognostic indicator.
Therefore, a revised version of the staging system for vulval cancer was offered by FIGO in 2009. Tumors larger than 2 cm are now stage IB, and the new FIGO stage II tumors comprise of lesions involving the lower urethra, vagina, or anus. The new stage 3 now contains 3 substages based on number and morphology of involved nodes rather than laterality.
The present study describes the migration of stages and compares outcomes of patients with vulval carcinoma previously staged using the FIGO 1988 staging with those staged using the new FIGO 2009 staging.
MATERIALS AND METHODS
After institutional review board approval, data were obtained from the Queensland Centre for Gynecological Cancer’s (QCGC) database. We identified 435 patients who received treatment at our center from 1988 to August 2009 for primary vulval carcinoma. All patients had to have a histological diagnosis of squamous cell carcinoma, adenocarcinoma, or Bartholin gland carcinoma. Patients with primary vulva melanoma, secondary malignancies to the vulva, or incomplete data to allow appropriate restaging were excluded from analysis. After application of the inclusion and exclusion criteria, 394 were available for analysis.
All individual patients’ charts were reviewed, and relevant information was extracted to confirm accuracy of initial FIGO 1988 staging. Then, all patients were assigned a FIGO stage based on the new FIGO 2009 system.
Pretreatment investigations for patients with vulval carcinoma at Queensland Centre for Gynecological Cancer included a preoperative computed tomographic scan of the groins, abdomen, and pelvis to detect gross nodal enlargement and metastatic lesions elsewhere. Metastasis was confirmed histopathologically wherever possible to determine the extent of the disease. In patients with histologically confirmed distant metastatic disease, surgical staging was not performed. In patients who had a radical vulvectomy or wide local excision, a clearance margin of 1 cm or wider was attempted. Groin lymphadenectomy was omitted if the depth of invasion was 1 mm or less. In patients with depth of invasion greater than 1 mm, lymphadenectomy included removal of the superficial and deep groin nodes with preservation of tissues above Scarpa fascia. Lymphadenectomy was unilateral if the lesion is unifocal, located greater than 2 cm from the midline, not located in the anterior portion of the labia minora, and when there was no clinical or radiological evidence of lymph node metastasis. During a transition period from 2007 to 2008, patients underwent a sentinel lymph node dissection using combined radioactive tracer and blue dye as described by de Hullu et al,8 followed by a full lymphadenectomy. From 2008, patients had only a sentinel lymph node dissection without a subsequent formal groin node dissection if the primary tumor was less than 4 cm in diameter, unifocal, not infected, and lymph node involvement was not suspected clinically or on imaging. Conversion to full lymphadenectomy was performed if there was any suspicion as to the accuracy of the sentinel lymph node technique. If positive lymph nodes were found, then full groin dissection was performed at subsequent operation. All histopathology reports and clinical management were routinely reviewed at our multidisciplinary tumor board meetings attended by a pathologist with a special interest in gynecological oncology, as well as gynecological, medical, and radiation oncologists.
Adjuvant radiotherapy was tailored according to clinical and histopathological findings. Patients with more than one positive groin lymph node, with macroscopic lymph node involvement, or with extracapsular spread were offered external beam radiation to the whole pelvis and the groins. Patients with close or positive surgical resection margins (<10 mm) at the vulva were offered another surgical resection or received adjuvant radiotherapy to the vulva. Radiotherapy was delivered to the midplane of the pelvis and inguinal regions using mixed electron and photon fields. The treatment was given using a wide anterior field covering the pelvis and groin, a narrower posterior field covering the pelvis and medial inguinal nodes, and small electron fields that supplemented the dose to lateral inguinal nodes that were excluded from the posterior field. A median dose of 45 Gy to the midplane of the pelvis in 1.8-Gy fractions was used. Chemotherapy was used in cases with palliative intent.
All patients were followed for 5 years. Of the 394 eligible patients, 16 patients were lost to follow-up, resulting in a median (interquartile range) follow-up period of 35.8 (12.1–69.8) months. The diagnosis of recurrence was based on radiological and histopathological evidence in one or more of the following sites: vulva, pelvis, and distant organs.
Descriptive statistics were used where relevant. With regard to prognosis, our end points were overall (OS) and relapse-free (RFS) survival. Overall survival was defined as the time difference between the date of diagnosis and the date of death or date of last follow-up for patients who were alive and censored. Relapse-free survival was calculated from the date of diagnosis to the time of first relapse or date last seen if there is no relapse. If the patient died because of this cancer without any documented relapse date, then the date of death was taken to be the date of relapse. All the events were censored at 5 years. We estimated OS and RFS using the Kaplan-Meier method, and the log rank test was used to test for significant differences between survival curves.
The patients’ mean age was 64 years (range, 25–99 years). Table 1 demonstrates the stage migration after application of the new (2009) FIGO staging system. All previously stage IA, IB, and IVB patients did not change their stage allocation. However, the new (2009) FIGO stage IB now also includes FIGO 1988 stage II, as patients with lesions greater than 2 cm were moved to this stage. Fifty-one patients were migrated from the 1988 stage II to the 2009 stage IB. Lower vaginal, urethral, or anal involvement is no longer stage III but migrated to stage II in the new staging system. Therefore, 6 patients (8%) migrated from stage III to stage II. The new FIGO stage III defines 3 substages. From the original 1988 stage III cohort (n = 78), 6 patients (8%) migrated to the new stage II, 38 patients (49%) to stage IIIA, 12 patients (15%) to stage IIIB, 17 patients (22%) to stage IIIC, and 5 patients (6%) to stage IVA. From the 1988 stage IVA cohort (n = 21), 1 patient (5%) migrated to IIIA, 8 patients (38%) to IIIB, 6 patients (28.5%) to IIIC, and 6 patients (28.5%) remained as IVA.
Table 2 displays survival probabilities (OS and RFS) broken down by FIGO 1988 and 2009 stages, respectively. As expected, there is no change in survival data in the old and new stages IA and IVB, as they are comprised of identical patients. New (2009) stage IB (173 patients) and previous (1988) stage IB (122 patients) had very similar survival, even if FIGO 2009 stage IB includes 51 patients who were stage 2 previously. Kaplan-Meier plots demonstrate that the difference in OS and RFS was diminished after application of the new FIGO staging system for stage IB and II diseases (Figs. 1, 2). Rates for OS in the patients with stage II disease were essentially unchanged when the 2009 and the 1988 FIGO staging systems were compared (Table 2).
The FIGO 2009 stage III includes 3 subgroups displaying distinctly different survival probabilities (Table 2). Overall survival and RFS at 5 years were similar for patients with stage IIIA and stage IIIB disease but significantly worse for patients with stage IIIC disease (Figs. 3, 4).
The new (2009) FIGO staging system on vulval cancer has mainly 2 implications. First, former stages IA, IB, and II are now combined to a large group of stage IA or IB disease, and only very few patients remain as stage II. Second, patients who formerly had a diagnosis of stage III disease are now substaged into stages IIIA, IIIB, and IIIC with distinct prognosis.
The number of patients in stage I in our sample of 394 patients increased from 234 (FIGO staging 1988) to 285 (FIGO staging 2009), which is a rise of 22%. All patients in formerly stage II migrated to stage IB in the new staging system. Hence, the number of patients in stage II decreased from 51 to 6 (decrease of 78%), which makes FIGO 2009 stage II a rare entity. At the same time, RFS and OS at 5 years remained stable.
Previous literature reported similar OS for the 1988 stage I and stage II disease, thus providing support to the proposed change in the 2009 staging.9 Similarly, our data indicate comparable RFS and OS between stages I and II. However, it must be noted that in our study, there were only 6 patients with FIGO 2009 stage II. Our finding on stage 2 is similar to the results reported by van der Steen et al.10 The number of patients in stage II changed very little. Fifteen of the 394 patients migrated from stage IVA to stages IIIA, IIIB, or IIIC. Interestingly, survival in the 3 substages is diverse. Whereas RFS and OS is similar and ranges between 50% and 60% at 5 years among patients with stage IIIA and IIIB diseases, prognosis for patients with FIGO 2009 stage IIIC vulval cancer is very poor. For this group of patients, RFS was 18% and OS was 17% at 5 years.
Diversification of the entire group of patients formerly stage III was the most important revision in the new staging system. Well-documented evidence suggested that lymph node status and nodal features are the most significant prognostic indicators.11–14 The decision of FIGO to omit laterality of lymph node metastasis in the new staging system was confirmed by a recent study by Fons et al,15 which concluded that bilateral existence of lymph node metastasis was not sufficient to qualify stage, whereas extracapsular spread seems to be the most valuable lymph node–associated prognostic factor for survival.
The low number of patients in stage IVA halved again by applying the FIGO 2009 staging criteria. The new criteria of ulcerated or fixed nodal disease facilitated a migration of patients from the former stage IVA (n = 21) to the 2009 stage IVA (n = 11). Overall survival remained poor at 13% for these patients.
Unfortunately, the FIGO 2009 vulval carcinoma staging system does not address the use of sentinel lymph node study and dissections, which is increasingly being used in clinical practice in developed nations.16 In fact, if a single node dissected on sentinel lymph node dissection is positive for tumor and a full dissection is not performed but adjuvant radiotherapy is used instead, then one can only classify it as “at least” stage IIIA, relying on clinical staging rather than surgical staging to assume there is no further disease.
The main aim of cancer staging is to determine the extent of disease to tailor treatment and compare patients for analyses. The present study suggests that the new 2009 FIGO staging system successfully addresses some of the concerns with the 1988 system and divides patients into more distinct groups with different survival probabilities.
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Keywords:Copyright © 2012 by IGCS and ESGO
Vulva; Carcinoma; FIGO; Staging; 2009