Impact of adjuvant therapy in lymph-node positive vulvar cancer: The AGO CARE 1 study.

Abstract

5007 Background: While the majority of patients with vulvar cancer can be cured by surgery alone, women with lymph-node metastases often show unfavorable outcome. Improved treatment strategies are therefore strongly needed. Methods: Patients with primary squamous-cell vulvar cancer treated at 29 gynecologic cancer centers in Germany between 1998 and 2008 were included in a centralized database and analyzed retrospectively. Results: A total of 1,637 patients were documented with a median follow-up of 121 months. UICC-Stage distribution was 597 (36.5 %) T1, 816 (49.8 %) T2, 160 (9.8 %) T3 and 31 (1.9 %) T4, 33 (2.0 %) were missing. 491 patients had lymph-node metastasis to the groins (N+). 214 N+ patients (43.6 %) developed recurrent disease within a median of 21.4 months. 190 N+ patients (38.7%) died, median overall survival (OS) was 43.4 months, compared to 212 months for node-negative patients. An increasing number of metastatic lymph-nodes was associated with shorter OS: 169 (34.4%) patients had 1, 101 (20.6%) patients 2, 62 (12.6%) patients 3 and 86 (17.5%) patients >3 positive lymph-nodes, with a corresponding OS of 22.4, 17.2, 18.4 and 10.2 months, respectively (for 73 patients the number of nodes was not available). 240 N+ patients were treated with adjuvant radiotherapy (85.8%) or radiochemotherapy (14.2%). Median OS in these patients was significantly longer (66.9 months) compared to N+ patients without adjuvant treatment (35.7 months), the corresponding hazard ratio (HR) was 0.72 (95 % CI: 0.53 - 0.97 p = 0.029). This impact on OS remained consistent in multivariate analysis adjusted for age, ECOG, stage, grading, invasion depth and number of positive nodes (HR 0.68; 95% CI: 0.49 - 0.94 p = 0.020) and was observed irrespective of the number of affected nodes. Conclusions: To this day, this is the largest multicenter study on vulvar cancer. Our findings strongly suggest that the unfavorable prognosis of patients with node positive vulvar cancer can be improved by adjuvant therapy irrespective of the number of affected nodes. As adjuvant radiochemotherapy was shown to be superior to radiotherapy alone in many other squamous cell carcinomas, we are preparing a prospective phase III trial in node-positive vulvar cancer (AGO-CaRE 2 trial).

Management of patients with vulvar cancer: a perspective review according to tumour stage

“…2006]. However, these results are supported by recently presented data from the largest retrospective multicenter study on vulvar cancer (AGO CaRE-1) with more than 1600 patients revealing an improvement of prognosis by adjuvant radiotherapy irrespective of the number of affected nodes [Mahner et al . 2012].…”

Vulvar carcinoma: dilemma, debates, and decisions

“…Moreover, adjuvant radiation did not significantly help women who had more than 12 LNs resected. In the recent and largest ever multicentric retrospective study by the AGO-CaRE-1, 54 adjuvant radiotherapy was associated with an improvement in prognosis irrespective of the number of involved lymph nodes.…”