Adjuvant therapy in lymph node-positive vulvar cancer: the AGO-CaRE-1 study

TY - JOUR

T1 - Adjuvant therapy in lymph node-positive vulvar cancer: the AGO-CaRE-1 study

AU - Mahner, Sven

AU - Jueckstock, Julia

AU - Hilpert, Felix

AU - Neuser, Petra

AU - Harter, Philipp

AU - de Gregorio, Nikolaus

AU - Hasenburg, Annette

AU - Sehouli, Jalid

AU - Habermann, Annika

AU - Hillemanns, Peter

AU - Fuerst, Sophie

AU - Strauss, Hans-Georg

AU - Baumann, Klaus

AU - Thiel, Falk

AU - Mustea, Alexander

AU - Meier, Werner

AU - du Bois, Andreas

AU - Griebel, Lis-Femke

AU - Woelber, Linn

N1 - © The Author 2014. Published by Oxford University Press.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Carcinoma, Squamous Cell

KW - Chemotherapy, Adjuvant

KW - Disease-Free Survival

KW - Female

KW - Germany

KW - Groin

KW - Humans

KW - Kaplan-Meier Estimate

KW - Lymph Nodes

KW - Lymphatic Metastasis

KW - Middle Aged

KW - Neoplasm Staging

KW - Prognosis

KW - Radiotherapy, Adjuvant

KW - Retrospective Studies

KW - Treatment Outcome

KW - Vulvar Neoplasms

U2 - 10.1093/jnci/dju426

DO - 10.1093/jnci/dju426

M3 - SCORING: Journal article

C2 - 25618900

VL - 107

JO - JNCI-J NATL CANCER I

JF - JNCI-J NATL CANCER I

SN - 0027-8874

IS - 3

ER -