Survival outcomes for patients with stage IVB vulvar cancer with grossly positive pelvic lymph nodes: Time to reconsider the FIGO staging system?

doi:10.1016/j.ygyno.2014.12.013

Gynecologic Oncology

Volume 136, Issue 2, February 2015, Pages 269-273

https://doi.org/10.1016/j.ygyno.2014.12.013 Get rights and content

Highlights

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Definitive treatment for patients with involved pelvic nodes led to favorable outcomes.
•
Overall survival was similar to that of patients with positive inguinal nodes.
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We recommend modification of the FIGO stage IVB classification.

Abstract

Objective

To evaluate treatment outcomes for patients with vulvar cancer with grossly positive pelvic lymph nodes (PLNs).

Methods

From a database of 516 patients with vulvar cancer, we identified patients with grossly positive PLNs without distant metastasis at initial diagnosis. We identified 20 patients with grossly positive PLNs; inclusion criteria included PLN 1.5 cm or larger in short axis dimension on CT/MRI (n = 11), FDG-avid PLN on PET/CT (n = 3), or biopsy-proven PLN disease (n = 6). Ten patients were treated with chemoradiation therapy (CRT), 4 with RT alone, and 6 with various combinations of surgery, RT or CRT. Median follow-up time for patients who had not died of cancer was 47 months (range, 4–228 months).

Results

Mean primary vulvar tumor size was 6.4 cm; 12 patients presented with 2009 AJCC T2 and 8 with T3 disease. All patients had grossly positive inguinal nodes, and the mean inguinal nodal diameter was 2.8 cm. The 5-year overall survival and disease specific survival rates were 43% and 48%, respectively. Eleven patients had recurrences, some at multiple sites. There were 9 recurrences in the vulva, but no isolated nodal recurrences. Four patients developed distant metastasis within 6 months of starting radiation therapy.

Conclusions

Aggressive locoregional treatment can lead to favorable outcomes for many patients with grossly involved PLNs that is comparable to that of grossly involved inguinal nodes only. We recommend modification of the FIGO stage IVB classification to more accurately reflect the relatively favorable prognosis of patients with PLN involvement.

Introduction

Advanced inguinal and pelvic lymph node (PLN) disease in vulvar cancer has consistently been found to correlate with disease recurrence and death [1], [2], [3], [4]. As the number of involved inguinal nodes increases, survival decreases and the likelihood of involved PLNs increases [5].

However, most data defining the prognosis of patients with positive PLNs date from the 1950s through 1980s, before postoperative regional radiation therapy (RT) became standard [6], [7], [8], [9]. Gynecologic Oncology Group (GOG-37) reported higher rates of disease-specific survival (DSS) with inguinal and pelvic RT as compared to PLN resection after radical vulvectomy and bilateral inguinal lymphadenectomy [10]. Patients who were treated with surgery alone and were found to have PLN metastases had a very poor survival rate of only 23% at 2 years [10].

As a result, the International Federation of Gynecology and Obstetrics and American Joint Committee on Cancer 2009 (FIGO/AJCC) classified patients with positive PLNs as IVB, grouping these patients with patients that have hematogenous metastases [11], [12]. However, outcome data for patients with positive PLNs treated with post-operative or definitive RT have been derived solely from studies of patients who had PLN dissection, usually without postoperative RT. Following the results of GOG-37, PLN resection fell out of favor for most patients with vulvar cancer, and patients who have inguinal nodal metastases are routinely treated with RT to the groin and pelvis. For this reason, diagnosis of microscopic PLN involvement is rare; patients who are diagnosed with stage IVB disease on the basis of PLN involvement usually have grossly enlarged nodes detected on imaging.

We therefore evaluated outcomes for patients with grossly positive PLNs to determine if classifying such disease as stage IVB remains appropriate in an era when RT is standard for most patients with inguinal node-positive vulvar cancer.

Section snippets

Patients

From a database of 516 unselected patients with histologically confirmed vulvar cancer treated at The University of Texas MD Anderson Cancer Center during the period from 1980 through 2010, we identified 20 patients who had evidence of gross PLN involvement. Two patients who had para-aortic lymph node metastases, which were defined as metastases in lymph nodes superior to the aortic bifurcation without distant metastases, were included in our analysis. PLNs were considered positive if they

Results

Patient, tumor, and treatment characteristics of the 20 patients who met our inclusion criteria are presented in Table 1. Median follow-up time for all patients in the cohort was 21 months and for patients who had not died of vulvar cancer was 47 months (range, 4–228 months). Most patients had extensive primary tumors with grossly involved inguinal nodes. The mean primary tumor size was 6.4 cm (median, 5.0 cm). Twelve patients presented with 2009 AJCC T2 and 8 with T3 vulvar disease. Seventeen

Discussion

Our data demonstrate that locoregional treatment with definitive or adjuvant RT can be curative for many patients with PLN-positive stage IVB vulvar cancer. Indeed, OS and disease-free survival for these patients approached those of patients with M0 disease with positive inguinal nodes (i.e., FIGO stage III disease) [14], [15].

The FIGO stage IVB designation for patients with positive PLNs initially resulted from the poor survival rates of a limited number of patients with positive PLNs

Conflicts of interest statement

MF reports personal fees from Novadaq and Ethicon. Otherwise, the authors declare that there are no other conflicts of interest.

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There were 18,207 eligible women. Median age at diagnosis was 64 years, and 31% diagnosed ≥75 years old were categorized as elderly. Most vulvar cancers were diagnosed at stage I and with squamous histology. Diagnosis with higher stage or non-squamous histology was more common in elderly vs. non-elderly patients (P < 0.001). Survival was 3.5 times worse in the elderly than the non-elderly (P < 0.0001). Risk of death for each 5-year increment in age increased by 22% for non-elderly and 43% for elderly patients (P < 0.0001). The prognostic value of comorbidity score, stage, regional node assessment and histology was smaller in elderly vs. non-elderly women (each P < 0.05). Adjuvant chemoradiotherapy (CTRT) use in the elderly vs. non-elderly was rare for stage I-II disease (3% vs. 2%) and more common for stage III-IV disease (6% vs. 43%), respectively (P < 0.0001). The survival disadvantage for elderly patients persisted following no adjuvant therapy, radiotherapy or chemotherapy alone, or CTRT (P < 0.0001). In stage III-IV disease, survival was superior following CTRT vs. radiotherapy when diagnosed <75 years (HR = 0.80, 95% CI = 0.69–0.93) but not in the elderly (HR = 0.99, P > 0.05).
Age-associated risk of death increased at different rates in vulvar cancer and was larger in elderly vs. non-elderly patients. The impact of other prognostic factors was smaller in elderly vs. non-elderly women. The survival benefit of CTRT over radiotherapy in stage III-IV did not extend to the elderly.
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Several methods for assessing depth of invasion have been proposed; however, currently depth of invasion is measured from the epithelial junction of the most superficial dermal papilla to the deepest point of tumor invasion.34,35 Multiple aspects of the FIGO staging system have been questioned and include the prognostic value of FIGO stage 1 and 2 disease because they do not differ in disease-specific survival and the uses of pelvic lymph node metastasis to define stage IVB disease.36,37 All patients should have a complete history and physical examination, complete blood count, assessment of liver and renal function, and evaluation of the vagina and cervix with cytologic smears.
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Thirty-three patients were identified. The median age at diagnosis was 64 years. The median long-axis radiographic diameter of the largest inguinal lymph node or lymph node mass was 2.5 cm (range, 1.4–8.7). Sixteen patients (48%) also had evidence of pelvic lymph node metastasis. The median radiation dose delivered to grossly involved nodes was 66.0 Gy (range, 60.0–70.0). The 3-year actuarial incidences of vulvar, groin, and distant recurrences were 24.2%, 17.7%, and 30.3%, respectively. With a median follow-up time of 28 months (range, 2–196), four patients (12%) had groin recurrence, of whom three also had vulvar recurrence. There were few major late adverse effects of regional radiotherapy. The 3-year overall survival rate was 51%.
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Survival outcomes for patients with stage IVB vulvar cancer with grossly positive pelvic lymph nodes: Time to reconsider the FIGO staging system?

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

Conflicts of interest statement

Gynecol Oncol

Gynecol Oncol

Am J Obstet Gynecol

Am J Obstet Gynecol

Gynecol Oncol

Int J Gynaecol Obstet

Int J Gynaecol Obstet Ther Adv Med Oncol

Int J Gynaecol Obstet

Gynecol Oncol

Eur J Radiol