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10.1245/s10434-007-9417-5
Annals of Surgical Oncology 14:2128-2132 (2007)
© 2007 Society of Surgical Oncology
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Original Article

The Definition of Optimal Inguinal Femoral Nodal Dissection in the Management of Vulva Squamous Cell Carcinoma

Tien Le1, Ramadan Elsugi1, Laura Hopkins1, Wylam Faught2 and Michael Fung-Kee-Fung1

1 Dept of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Ottawa, Ottawa, Ontario
2 Dept of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alberta, Edmonton, Alberta

Correspondence: Address correspondence and reprint requests to: Tien Le; E-mail: tle{at}ottawahospital.on.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Objectives: To reject the hypothesis that the number of nodes removed at time of surgical staging for vulva cancer is not an important prognostic factor.

Methods: Retrospective chart reviews were carried out from 1980–2004 to identify patients with squamous cell vulva carcinoma treated with radical vulvectomy and bilateral inguinal femoral lymph node dissection. Patients’ demographics, disease characteristics, the number of lymph nodes removed at surgery, and standard oncologic outcomes were recorded. Cox proportional hazard models were built to model times to clinical progression and death using predictor variables of: age, tumor size and maximum depth of invasion, resection margin status, and total number of nodes removed.

Results: Fifty-eight patients were identified. The median lesion size was 3.5 cm. The median depth of invasion was 7.5 mm. The 20th percentile for total number of lymph nodes removed was 10. Adjuvant radiation therapy was given in 31% of patients. At a median follow-up of 37 months, recurrence was observed in 17 patients (29.3%). Cox regressions showed the total number of nodes removed less than 10 to be the only significantly predictive of shorter time to first progression (HR = 12.88, 95% CI = 1.47–112.89, P = .021) and shorter disease specific survivals (HR = 11.41, 95% CI = 2.21–58.86, P = .004) (HR, hazard ratio; CI, confidence interval).

Conclusion: The total number of nodes removed at time of surgical staging is an independent survival prognostic factor. A total of at least 10 nodes from a bilateral dissection can be used to define an optimal evaluation.

Key Words: Vulva cancer • Nodal dissection • Surgical staging • Prognosis


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Vulva cancer represents between 3 and 5% of all gynecologic malignancies1 and about 1% of all cancer in women with an incidence rate of 1 to 2 in 100,000.2 Due to the tumor rarity, large prospective randomized trials to guide management are few in this disease. Since 1988, The Federation International of Gynecologists and Obstetricians (FIGO) have recommended the adoption of surgical-staging system in vulva cancer due to the clinical difficulties in diagnosing inguinal nodal metastasis. The current Canadian practice guideline on the management of squamous cell cancer of the vulva also recommended surgical nodal assessments in clinical stage 1 to 3 vulva cancer.3 One important component of the staging procedure includes a comprehensive surgical assessment of the inguinal femoral lymph nodes as this has been shown to be a strong prognostic indicator forming the basis for recommendations of subsequent adjuvant radiotherapy.4,5 Over the years, there has been a consistent trend toward less radicality in the operative management of invasive squamous cell carcinoma of the vulva.6 Inguinal nodal dissections can be complicated by significant postoperative complications such as infections, symptomatic lymphocysts, wound breakdown, as well as chronic lymphedema of the extremities that seriously interfere with patients’ quality of life.7–9 To limit the morbidities associated with this procedure, some authors have recommended either the use of sentinel node sampling10,11 or superficial nodal dissection with saphenous vein preservation.12,13 Currently, due to the lack of established long-term oncologic outcomes as well as experience with sentinel node procedures in most centers, this approach remains experimental. Patients undergoing superficial inguinal node dissections had been reported to have a slight but significant increase in the rate of inguinal recurrences compared to those having a complete groin dissection.14,15 With the expected poor salvage rate of inguinal nodal recurrence, the increase in recurrence rate observed after superficial groin node dissection is unacceptable, and the procedure cannot be regarded as a standard of care for most patients with vulva carcinoma.

At present, despite the well-accepted importance of the inguinal node status, no study has clearly defined the optimal way to assess lymph node status, and surgical practice varies significantly among gynecologic oncologists.16 Reviewing most retrospective surgical-staging series, the minimal number of inguinal nodes removed ranged from three to five with a median of seven nodes removed at time of surgical staging from each inguinal area.14 We attempted to correlate the number of nodes removed at surgical staging to patients’ prognosis to assess the optimal nodal yield for adequate evaluation of the inguinal area. We also sought to reject the hypothesis that the number of nodes removed at time of surgical staging for vulva cancer is not an important prognostic factor.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A retrospective review of all patients diagnosed with squamous cell carcinoma of the vulva treated with radical vulvectomy and bilateral inguinal femoral nodal dissection at the University of Ottawa was carried out from 1980–2004 after research ethics board approval. Radical vulvectomy was performed to obtain at least a 1 cm margin around the tumor with the deep margin being the perineal fascia. Bilateral labia majora and minora including the clitoris were included in the surgical specimen. Each inguinal femoral node dissection was performed using separate incisions from the vulva incision to remove nodal tissues in the region of the fossa ovalis. Patients treated with just wide local excisions or those had only unilateral inguinal nodal dissection were excluded as there were wide differences in surgical procedures used to address the primary vulva lesion and the criteria used to define a midline lesion. Eligible patients were identified through the Ottawa Regional Cancer Center registry. Throughout this time period, significant variations in surgical practice to assess the inguinal area existed at our institution because a number of surgical oncologists had differing philosophies of treatments and surgical practices. Relevant patients’ demographics, together with disease-related characteristics, were abstracted from cancer clinic charts with cross references made to the electronic hospital patient information database to ensure completeness and accuracy of information. Due to the long time span covered by this study, formal pathology reviews of the histology were not performed.

Descriptive statistics were used to summarize demographic variables for the group. Cross tabulations were used to test for associations between categorical variables. Cox proportional hazard models were built to model times to clinical progression and disease-related death using predictor variables of: age, tumor size, and maximal depth of invasion, resection margin status, and total number of nodes removed. These variables were chosen based on previous publications confirming their prognostic values in predicting recurrent disease. Backward stepwise variable selection strategy was used to obtain the most parsimonious model. The Kaplan-Meier method was used to estimate overall survivals. The log-rank test was used to compare survival curves. SPSS software (SPSS for Windows, Rel. v13. Chicago: SPSS Inc.) was used for data management and all subsequent statistical analysis. All P values less than .05 were considered to be statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Over this 24-year period, 155 patients with vulva carcinoma were treated at our institution. Preoperative radiation was not used during this time period. Of these patients, 58 had squamous cell carcinoma treated with radical vulvectomy and bilateral inguinal femoral node dissection all using triple incision technique as part of their primary surgical management were selected forming the basis for this report. No sentinel lymph node procedure was performed in this time period. The median age of the group was 71.3 (range from 28.33–90.86). All patients had macroscopically visible lesion with the mean largest lesion dimension of 3.75 cm. Seven patients (12.1%) presented with foul-smelling discharge, and another 14 patients (24.1%) had significant perineal pain as their initial presentation. Nine patients (15.5%) had clinically documented enlarged inguinal lymph nodes. Three patients had superficial involvement of distal urethra, and four patients had tumor spreading to the distal anus and rectovaginal septum. Resection margin was positive for high-grade vulva intraepithelial lesions in 11 patients (19%). The median maximum depth of invasion was 7.5 mm. The mean number of lymph node harvested was 7.8 on the right side (range 1–19) and 7.9 (range 1–18) on the left side, respectively. The median number of lymph nodes removed was 14 with the 20th percentile number of total nodes removed being 10. Nodal metastasis was documented in 21% of patients.

Significant postoperative complications requiring hospital readmission or reoperation were encountered in 19 patients (32.7%). Adjuvant radiation therapy was administered in 18 patients (31%) for nodal metastasis and/or positive resection margins at a median dose of 4500 cGy to the pelvis and perineum with curative intent. Patients with negative inguinal nodes and clear resection margins were followed expectantly with no adjuvant radiotherapy. Significant radiation-induced side effects requiring modifications or delays of the treatment plans were observed in 13 patients (22.4%). After finishing the primary treatment, 56 patients had clinically complete response. Two remaining patients progressed during treatment.

At a median follow-up of 37 months, 17 recurrences were observed (29.3%). Six were local recurrences on the perineum, three were groin recurrences, two had extra pelvic recurrences, and six had recurrences in both pelvic and extra pelvic locations. All local perineal recurrences were successfully treated with radical re-excisions. At time of latest follow-up, 10 patients have died from their disease (17.2%). Of the 18 patients treated with radiotherapy postoperatively, six recurrences (33%) were noted. Four of these recurrences involved extra-pelvic locations, one recurrence was in the inguinal area, and the other one recurred locally on the perineum. At the last follow-up of these patients, five patients have died of their disease and one patient is currently disease free.

In the Cox model examining the time to first clinical recurrence, the total number of lymph nodes removed was the only statistically significant predictor in the multivariate analysis (HR = 0.86, 95% CI = 0.74–0.99, P = .04) (HR, hazard ratio; CI, confidence interval). Age, tumor size, maximal depth of invasion, and resection margin status were not significantly predictive. Using a cut-off value of at least 10 nodes removed (based on the 20th percentile value in our dataset) to define the optimal dissection of the inguinal areas, the model again showed the total number of nodes removed of less than 10 being the only significantly predictive of shorter time to first progression (HR = 12.88, 95% CI = 1.47–112.89, P = .021) and shorter disease specific survivals (HR = 11.41, 95% CI = 2.21–58.86, P = .004). Figure 1Go plots the estimated survival functions for the two groups adjusted for the above covariates in the Cox model.


Figure 1
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  		FIG. 1. Survival curves for patients with more or less than 10 harvested inguinal nodes at time of surgical staging.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The extent of inguinal femoral nodal involvement is an important prognostic variable in patients with vulva carcinoma as expected 5-year survival decreases from 90% with uninvolved lymph nodes to 24% when five or six lymph nodes are involved.4,17 Adjuvant radiation therapy is often recommended for patients with two or more metastatic nodes18 or if there was extensive extracapsular nodal extension3 to improve both local control and overall survival. Radiation therapy has even been suggested to be of potential benefits in patients with only one metastatic node when a less extensive lymph node resection (arbitrarily defined as less than 12 nodes removed) has been performed.19 The optimal definition of an adequate inguinal dissection has not been clearly defined to guide clinical practice, and surgical practices vary widely among oncologists, as such standardized procedures with clearly defined and measurable goals are needed.16 In our case series, the total number of nodes harvested during primary surgical management proved to be an independent predictor of both progression-free and overall survivals. It is conceivable that the more nodes that are removed, the less chance there is of missing an occult nodal metastasis, which could affect timely treatment, thereby reducing recurrence. Complete lymphadenectomy may also have a therapeutic effect as has been shown in endometrial cancer.20,21 The 20th percentile of total number of nodes removed in our study was 10, and this was arbitrarily chosen as the minimal nodal count to define an optimal nodal resection. This figure was consistent with the median nodal counts in other reports of vulva cancer patients similarly treated surgically.

When patients were divided into those with less than 10 nodes and those with more than 10 nodes removed from both inguinal areas, patients with a fewer number of nodes had a significant inferior oncologic outcome and a higher recurrence rate after adjusting for other potential confounders. A more radical groin dissection can result in a better pickup of occult metastatic disease resulting in proper application of adjuvant pelvic radiotherapy lessening the chance of perineal recurrence post-radical vulvectomy where the surgical site was usually encompassed within the radiation treatment portal. Furthermore, as inguinal recurrences after surgical evaluation are expected to have an universally poor prognosis14 and adjuvant radiotherapy can salvage a significant portion of patients with inguinal metastasis,17 we recommend a complete inguinofemoral lymphadenectomy in all patients with vulva carcinoma until the sentinel node procedures are better established with regard to long-term safety and patient selection criteria are clearly defined. Alternatively, lymphatic mapping can be used to identify the sentinel node that can be processed using ultrastaging protocol to detect micrometastasis in combination with complete inguinal lymphadenectomy in those with sentinel nodal spread.

Similar findings of more complete nodal dissection assessed by using nodal count resulting in improved outcomes have also been observed in endometrial cancer with poorly differentiated tumors where adjuvant radiation therapy is also commonly used.21 One should recognize that this is one prognostic factor in the management of vulva cancer that can be directly controlled by the surgical oncologist with regard to the extensiveness of surgical assessment. Similar observations of improved outcomes with more comprehensive evaluation of regional nodes as defined by a higher nodal count have also been reported in other tumor sites such as gastric carcinoma.22

The difficulties in using nodal count in assessing the quality of surgical dissection lies in the obvious variation in the number of existing nodes among patients as well as the effort and techniques used by pathologists to process the surgical specimen. A standardized protocol for pathologic specimen processing is needed. As per our findings in the multivariate analysis, we propose to define optimal inguinal nodal dissection using a cut-off value of at least 10 nodes in total for patients undergoing bilateral inguinal femoral lymphadenectomy. This criterion will need to be validated in larger datasets, ideally in a prospective manner.

The limitations of our study include its retrospective design as well as the long time period that this report covers. Many different surgical oncologists have worked at this center during this time period, and treatment paradigms in vulvar cancer have evolved. Selection bias in our dataset could not be eliminated. We have attempted to adjust for some previously identified important confounders such as age, lesion size, depth of invasion, and marginal involvements,5,23 but due to the rarity of the disease and the small number of available patients, more detailed adjustments could not be performed limiting the power of the analysis.

In summary, we document the importance of performing as complete an inguinal nodal dissection as possible in patients undergoing radical vulvectomy for vulva carcinoma. We believe a standardized surgical procedure allowing for a complete and comprehensive evaluation of the inguinal area is crucial for influencing patients’ prognosis by timely administration of adjuvant radiotherapeutic treatment. Nodal count should be an important part of the overall evaluation of the quality of surgery performed in the staging and treatment planning for patients with vulva cancer.

Received for publication February 10, 2007. Accepted for publication March 16, 2007.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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