Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.
BACKGROUND
Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer.


METHODS
We randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery).


RESULTS
Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P=0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival.


CONCLUSIONS
Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.)
Vergote
Ignace
I
University Hospitals, K.U. Leuven Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Herestraat 49, B-3000 Leuven, Belgium. ignace.vergote@uzleuven.be
Tropé
Claes G
CG
Amant
Frédéric
F
Kristensen
Gunnar B
GB
Ehlen
Tom
T
Johnson
Nick
N
Verheijen
René H M
RH
van der Burg
Maria E L
ME
Lacave
Angel J
AJ
Panici
Pierluigi Benedetti
PB
Kenter
Gemma G
GG
Casado
Antonio
A
Mendiola
Cesar
C
Coens
Corneel
C
Verleye
Leen
L
Stuart
Gavin C E
GC
Pecorelli
Sergio
S
Reed
Nick S
NS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D016016:Proportional Hazards Models; D011788:Quality of Life; D016019:Survival Analysis
D000970:Antineoplastic Agents