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.

Figure 1.

Patient characteristics and treatment diagram. CT = chemotherapy; LN = lymph node; Tx = therapy; RT = radiotherapy; RCT = radiochemotherapy.

Figure 2.

Lymph node status and outcome. A) Progression-free survival. B) overall survival. P values were calculated using the two-sided log-rank test. CI = confidence interval; HR = hazard ratio; N- = node-negative; N+ = node-positive; OS = overall survival; PFS = progression-free survival.

Figure 3.

Progression-free survival (A) and overall survival of (B) node-positive patients with regard to adjuvant radiotherapy to the groins +/-pelvis +/-vulva. P values were calculated using the two-sided log-rank test. CI = confidence interval; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; Tx = therapy.

Figure 4.

Forest plot of progression-free survival in nodal subgroups with regard to adjuvant radiotherapy to the groins +/-pelvis +/-vulva. Results unadjusted (A) and confounder-adjusted by inverse probability of treatment weighting (B). P values were calculated using the two-sided log-rank test. CI = confidence interval; HR = hazard ratio; LN = lymph node; PFS = progression-free survival.