Role of lymphadenectomy in the management of grossly apparent advanced stage epithelial ovarian cancer

doi:10.1016/j.ajog.2006.06.068

American Journal of Obstetrics and Gynecology

Volume 195, Issue 6, December 2006, Pages 1862-1868

https://doi.org/10.1016/j.ajog.2006.06.068 Get rights and content

Objective

The purpose of this study was to determine the factors that are related to the performance of lymph node assessment and its impact on prognosis in ovarian cancer.

Study design

This was a retrospective analysis of stage IIIC/IV epithelial ovarian cancer in patients who had undergone primary surgery between 1994 and 1998. Simple statistics and univariate and multivariable analysis were performed.

Results

Two hundred nineteen patients met the inclusion criteria; lymph node assessment was performed for 93 of these patients (41%). Sixty-one patients (65.5%) underwent complete pelvic and para-aortic lymphadenectomy, and 32 patients (34.5%) underwent a more limited lymph node sampling. In patients with residual disease >1 cm, lymph node assessment was an independent predictor of outcome. In this same subgroup, lymphadenectomy appeared to be superior to lymph node sampling (5-year overall survival, 50% (lymphadenectomy) vs 33% (lymph node sampling) vs 29% (no lymph node assessment); P = .01). Considering survival of the subgroup who underwent lymph node assessment, we observed a significantly worse outcome for those with lymphatic involvement (5-year overall survival, 31.5% [positive for nodal metastases] vs 54% [negative for nodal metastases]; P = .003). Although multiple factors were correlated with the decision to perform lymph node assessment in univariate analysis, only the surgeon (P < .001), low residual disease (P = .004), American Society of Anesthesiology 1 or 2 (P = .004), and the absence of carcinomatosis (P = .0002) were independent factors in the multivariable analysis. Further, if lymph node assessment was performed, the decision to do lymphadenectomy versus lymph node sampling was associated independently with the surgeon (P < .001), low residual disease (P < .001), and patient age of <65 years (P < .001).

Conclusion

Removal of obviously involved lymph nodes in patients with residual disease near 1 cm and lymphadenectomy for patients with complete or near complete resection of abdominal disease appears to be justified. A lack of standard recommendation in advanced ovarian cancer results in wide variations that are based on individual preference in addition to logical factors.

Section snippets

Methods

All a diagnoses of Federation of Obstetricians and Gynecologists (FIGO) stage IIIC or IV primary epithelial ovarian cancer stage for patients who underwent operation primarily at Mayo between January 1, 1994, and December 31, 1998, were recorded and used for the purpose of this study. Patients who had undergone previous surgical exploratory procedures elsewhere and patients who were referred to our institution after having received initial chemotherapy treatment before surgery were excluded.

Results

Two-hundred nineteen patients with stage IIIC/IV ovarian cancer met the inclusion criteria. The mean age was 65 years (range, 24-87 years), with a mean follow-up period of 3 years (95% CI, 2.68-3.25). Overall 5-year survival was 26%. Patient and tumor characteristics are given in Table I. The various cytoreductive procedures that were performed during the primary surgery are summarized in Table II. Five patients (2%) died within 30 days from the surgery date. A total of 12 patients (5.5%) did

Comment

A recent large multicenter randomized trial compared outcomes in patients who had undergone optimal cytoreduction (<1 cm) after systematic LND versus the removal of only macroscopically involved lymph node (>1 cm) in stage IIIB-IV ovarian cancer.⁸ They found no survival benefit for LND, although they reported an observed increase in time to recurrence. These results are in disagreement with previous literature that supports the benefit of thorough staging and debulking of the retroperitoneal

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To appraise clinical outcomes of systematic lymphadenectomy in women with ovarian cancer based on stage, control group and type of chemotherapy.
A literature search was conducted on SCOPUS, PUBMED, COCHRANE, MEDLINE, and WEB OF SCIENCE databases. All comparative studies that assess outcomes of systematic lymphadenectomy in patients with ovarian cancer were eligible. Overall survival was analyzed by pooling log hazard ratio (HR) and standard error of multivariable Cox regression models. MOGGE Meta-analysis Matrix is a novel illustration tool that was used to demonstrate multiple subgroup analyses of included studies.
Twenty-two studies were eligible. Systematic lymphadenectomy was associated with better overall survival, that was close to significance, compared to control group (HR 0.93, 95 %CI 0.86–1.00). Among women treated with adjuvant chemotherapy, overall survival improved in women with stage IIB-IV who underwent systematic lymphadenectomy (HR 0.91, 95 %CI 0.84−0.99) and was most significant among patients with stage III to IV (HR 0.85, 95 %CI 0.73−0.99). Systematic lymphadenectomy did not improve survival in women who received neoadjuvant chemotherapy (HR 0.97, 95 %CI 0.73–1.29). Systematic lymphadenectomy was associated with improved progress-free survival compared to control group (HR 0.88, 95 %CI 0.79−0.99).
Although data from clinical trials do not support role of systematic lymphadenectomy in advanced ovarian cancer, overall data conveys stage-specific survival benefit. Further clinical trials may be warranted to assess substage survival outcomes in women with advanced stages.
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Citation Excerpt :
It is the cancer among genital cancers in which spread via lymph nodes is most commonly seen.4 Lymph node metastasis is related with poor prognosis.1,5–8 It is present in 10%-15% of the cancers that are localized in ovary and in 50% of advanced-stage cancers.9
Lymph node metastasis has a significant contribution to the prognosis of epithelial ovarian cancer but the role of lymph node dissection in treatment is not clear. In this study, we aimed to retrospectively determine the effect of the number and localization of lymph nodes removed and the number of metastatic lymph nodes on survival.
In this study, we retrospectively reviewed the data of 378 patients (210 patients with lymph node dissection and 168 patients with no dissection) who underwent primary surgery between 2004 and 2014 in various centers with epithelial ovarian cancer diagnosis and followed up in our medical oncology clinic. Demographic and histopathologic features, stage, Ca 125 levels, chemotherapy responses of these patients were examined and survival analyzes were performed.
The median age of the patients was 52 years (range 16-89) and median follow-up duration was 39 months (range 1-146). During the analysis, 156 patients (41%) died and 222 patients (59%) were alive. Patients who underwent lymphadenectomy had significantly improved progression free survival (PFS) (18 vs 31 months, P < 0.05) and overall survival (OS) (57 vs 92 months, P < 0.05). OS was longer in patients with >10 lymph nodes removed compared to patients with 1-10 lymph nodes removed (P = 0.005). Survival was found to be longer in patients with pelvic and paraaortic lymph node dissection compared to patients with only pelvic lymph node dissection (P < 0.05). Patients in stage I-II had no difference in PFS and OS. Patients in stage III-IV had no difference in PFS but there was a significant difference in OS (P = 0.02).
It may be a therapeutic effect of lymphadenectomy in advanced stage ovarian cancer. The number of lymph nodes removed and the removal of the paraaortic lymph nodes may also contribute to the treatment.
Surgery for advanced stage ovarian cancer: Article drafted from the French Guidelines in oncology entitled “Initial management of patients with epithelial ovarian cancer” developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa
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La chirurgie de cytoréduction complète est la pierre angulaire du traitement des cancers avancés de l’ovaire avec la chimiothérapie. La qualité de l’exérèse chirurgicale est le facteur pronostique essentiel et une chirurgie complète doit donc être réalisée (grade A) dans un centre expert (grade B). La chirurgie des stades IV est possible et apporte un bénéfice en cas de chirurgie complète péritonéale abdominale (NP3). Il est recommandé de réaliser des lymphadénectomies lombo-aortiques et pelviennes en cas de suspicion clinique ou radiologique d’adénopathie métastatique (grade B). En l’absence d’adénopathie suspecte clinique ou radiologique et en cas de chirurgie péritonéale complète lors d’une chirurgie initiale, il est possible de ne pas réaliser de lymphadénectomie parce que cela ne modifie pas le traitement médical ni la survie globale (grade B). La chimiothérapie néo-adjuvante pourra être proposée en cas de : résection complète non envisageable en chirurgie première (grade B); altération de l’état général ou co-morbidités ou patiente âgée (diminution de la morbidité et amélioration de la qualité de vie) (grade B) ; stade IV notamment avec lésions intrahépatiques multiples ou métastases pulmonaires ou ascite importante avec miliaire (grade B). En cas de cancer de l’ovaire de stade FIGO III ou IV diagnostiqué par une biopsie lors d’une laparotomie préalable, une chimiothérapie néo-adjuvante et une chirurgie d’intervalle sont à privilégier (grade C). En cas de chirurgie palliative ou de constat peropératoire de l’impossibilité de réaliser une chirurgie à résidu nul, il n’existe pas de données sur le type de geste chirurgical à effectuer ayant montré un impact sur la survie sans récidive ou sur la qualité de vie. Il est recommandé de décrire la carcinose péritonéale avant toute exérèse ainsi que les résidus tumoraux en fin de chirurgie (taille, localisation et raison de la non-extirpabilité) (grade B). Il est recommandé d’utiliser un score de carcinose péritonéal permettant d’évaluer de façon objective la charge tumorale comme le Peritoneal Carcinosis Index (PCI) (grade C). L’utilisation d’un compte rendu opératoire standardisé est recommandée (grade C).
Debulking surgery is the key step of advanced stage ovarian cancer treatment with chemotherapy. The quality of surgical resection is the main prognosis factor, thus a complete resection must be achieved (grade A) in an expert center (grade B). Surgery for stage IV is possible and has a benefit in case of complete peritoneal resection (LoE3). Pelvic and aortic lymphadenectomies are recommended in case of clinical or radiological suspicious lymph nodes (grade B). In absence of clinical or radiological suspicious lymph nodes and in case of complete peritoneal resection during initial debulking surgery, lymphadenectomy can be omitted because it won’t change nor medical treatment nor overall survival (grade B). Neoadjuvant chemotherapy can be proposed in case of: impossibility to perform initial complete surgical resection (grade B) ; alteration of general state or co-morbidities or elderly patient (in order to decrease morbidity and increase quality of life) (grade B); stage IV with multiple intra-hepatic or pulmonary metastasis or important ascites with miliary (grade B). In case of stage III or IV ovarian cancer diagnosed on a biopsy during prior laparotomy, a neoadjuvant chemotherapy and interval debulking surgery should be preferred (grade C). In case of palliative surgery or peroperative impossibility to perform a complete resection, no data regarding the type of surgery to perform influencing survival or quality of life is available. Peritoneal carcinosis description before resection and residual disease at the end of the surgery should be reported (size, location and reason of non-extirpability) (grade B). A score of peritoneal carcinosis such as Peritoneal Carcinosis Index (PCI) should be used in order to objectively evaluate the tumoral burden (grade C). A standardized operative report is recommended (grade C).
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: Presented at the Thirty-Second Annual Meeting of the Society of Gynecologic Surgeons, April 3-5, 2006, Tucson, AZ.

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Transactions from the Thirty-Second Annual Scientific Meeting of the Society of Gynecologic SurgeonsRole of lymphadenectomy in the management of grossly apparent advanced stage epithelial ovarian cancer

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Comment

Am J Obstet Gynecol

Gynecol Oncol

Gynecol Oncol

Ann Oncol

Gynecol Oncol

Gynecol Oncol

Cancer statistics 2005

CA Cancer J Clin

Transactions from the Thirty-Second Annual Scientific Meeting of the Society of Gynecologic Surgeons
Role of lymphadenectomy in the management of grossly apparent advanced stage epithelial ovarian cancer