Adjuvant Therapy in Lymph Node–Positive Vulvar Cancer: The AGO-CaRE-1 Study

Abstract

Background:Women with node-positive vulvar cancer have a high risk for disease recurrence. Indication criteria for adjuvant radiotherapy are controversial. This study was designed to further understand the role of adjuvant therapy in node-positive disease.Methods:Patients with primary squamous-cell vulvar cancer treated at 29 gynecologic cancer centers in Germany from 1998 through 2008 were included in this retrospective exploratory multicenter cohort study. Of 1618 documented patients, 1249 had surgical groin staging and known lymph node status and were further analyzed. All statistical tests were two-sided.Results:Four hundred forty-seven of 1249 patients (35.8%) had lymph node metastases (N+). The majority of N+ patients had one (172 [38.5%]) or two (102 [22.8%]) positive nodes. The three-year progression-free survival (PFS) rate of N+ patients was 35.2%, and the overall survival (OS) rate 56.2% compared with 75.2% and 90.2% in node-negative patients (N-). Two hundred forty-four (54.6%) N+ patients had adjuvant therapy, of which 183 (40.9%) had radiotherapy directed at the groins (+/-other fields). Three-year PFS and OS rates in these patients were better compared with N+ patients without adjuvant treatment (PFS: 39.6% vs 25.9%, hazard ratio [HR] = 0.67, 95% confidence interval [CI[= 0.51 to 0.88, P = .004; OS: 57.7% vs 51.4%, HR = 0.79, 95% CI = 0.56 to 1.11, P = .17). This effect was statistically significant in multivariable analysis adjusted for age, Eastern Cooperative Oncology Group, Union internationale contre le cancer stage, grade, invasion depth, and number of positive nodes (PFS: HR = 0.58, 95% CI = 0.43 to 0.78, P < .001; OS: HR = 0.63, 95% CI = 0.43 to 0.91, P = .01).Conclusion:This large multicenter study in vulvar cancer observed that adjuvant radiotherapy was associated with improved prognosis in node-positive patients and will hopefully help to overcome concerns regarding adjuvant treatment. However, outcome after adjuvant radiotherapy remains poor compared with node-negative patients. Adjuvant chemoradiation could be a possible strategy to improve therapy because it is superior to radiotherapy alone in other squamous cell carcinomas.

The Impact of Age on the Prognosis of Vulvar Cancer

“…Panici et al showed a correlation between age and OS, but not with DFS [34,35]. The relative survival, which is the difference in comparison with a non-affected sample patient group, was not analysed.…”

Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: A National Cancer Data Base (NCDB) analysis

“…Interestingly, in the present analysis, patients with lymph node positive ratio ≤20% still received a benefit from chemotherapy, perhaps reflective of the persistent risk of distant microscopic disease in node-positive patients. Retrospective analyses from Germany and SEER have similarly argued for adjuvant radiotherapy in patients even with 1 involved lymph node, demonstrating a survival benefit [28,29]. Studies regarding the use of adjuvant chemotherapy for nodepositive vulvar cancer, either given concurrently with radiation or alone, are limited to small retrospective series [30][31][32][33].…”

Correlation of Isotope Count With Sentinel Node Positivity in Vulvar Cancer

“…In vulvar cancer however, often multiple, up to 7 SLN nodes per groin are identified 11 and are consequently excised to guide further groin treatment. 12,13 Thereby, morbidity potentially is increased with recurrent seroma, lymphedema, wound breakdown, or erysipelas despite of node-negative disease. Theoretically, the SLN with the highest isotope count (''hottest'' SLN) should be most likely to harbor tumor cells.…”