Lymph node metastasis is one of the main metastatic pathways of ovarian cancer, with a total probability of 20 to 41%, while retroperitoneal lymph node metastasis rate of advanced ovarian cancer is as high as 50 to 75% [12, 13]. There are three main ways to remove lymph nodes: lymph node sampling, removal of palpable nodes and systematic/radical lymphadenectomy. Systemic retroperitoneal lymphadenectomy refers to the complete removal of lymphatic and adipose tissue around the abdominal aorta and inferior vena cava, as well as the pelvic cavity on both sides, generally last to the level of the left renal vein, the lower boundary to the inguinal ligament level. And bilateral psoas, anterior longitudinal ligament of the spine and sacral periosteum should be exposed and visible after surgery [14].
Some studies indicated survival benefit of lymphadenectomy in patients with early-stage ovarian cancer. Chan JK et al. [15] conducted a retrospective study on 6686 patients with stage I ovarian cancer in 2007, and showed that lymphadenectomy improved the 5-year survival rate of epithelial ovarian cancer patients with non-clear cell carcinoma.
However, results of studies on whether systemic retroperitoneal lymphadenectomy can improve the prognosis of advanced ovarian cancer patients were different. The majority of early retrospective studies have suggested a favorable prognosis of systematic retroperitoneal lymphadenectomy in patients with macroscopically completely resected advanced ovarian cancer. du Bois A et al. [6] reviewed 1942 epithelial ovarian cancer patients, the results showed that among the 996 patients without residual tumor, the 5-year survival rate was significantly higher in the group receiving lymph node resection of different degrees than that in the group without lymph node resection (67.4% vs 59.2%, P = 0 .0166); besides, lymphadenectomy showed a significant survival influence on those patients without clinically suspected nodes (the median OS was 108 vs 83 months, P = 0.0081); meanwhile, patients with small residual tumor also showed a positive effect on lymphadenectomy regardless of clinical lymph node status. A retrospective study consisting of 488 patients with untreated advanced ovarian cancer also revealed that among patients with optimal or suboptimal cytoreduction, 5-year survival in patients who underwent lymphadenectomy was higher than the patients who did not (P = 0.05, P < 0.005) [7]. Aletti GD et al. [8] also demonstrated a favorable prognosis in the stage IIIC/IV epithelial ovarian cancer patients who received lymphadenectomy, in which 5-year OS was 50% (lymphadenectomy) vs 33% (lymph node sampling) vs 29% (no lymph node assessment) (P = 0.01). Chan JK et al. [9] reported that among stage III-IV ovarian cancer patients, expanding the scope of lymph node resection can improve the survival rate. A comparative study on patients with advanced ovarian cancer (stage IIIC-IV) and no residual disease showed that systematic pelvic and para-aortic lymphadenectomy significantly improved patients’ survival (P = 0.02) [10]. Burghardt et al. [16] analyzed stage III ovarian cancer patients, also found a superior prognosis of lymphadenectomy. Kikkawa et al. [17] indicated that the incidence of death in the lymphadenectomy group was lower than that in the control group (Hazard Ratio: 0. 677; P = 0. 0497).
However, a number of studies have reported that systematic pelvic and para-aortic lymphadenectomy has no benefit to patients’ prognosis.
Spirtos NM et al. [18] reviewed the role of retroperitoneal lymphadenectomy in patients with stage IIIA-IVA advanced ovarian cancer who underwent suboptimal cytoreductive surgery (residual tumor was < 1 cm), the result uncovered that patients who underwent removal of macroscopically positive lymph nodes had no superiority in terms of benefits than those with microscopically positive and/or negative lymph nodes. Sakai K et al. [3] also reported among the advanced ovarian cancer patients with optimal cytoreduction (residual tumor < 1 cm), there was no significant difference in 5-year OS (59 vs 62.9%, P = 0.853) or PFS (41.9 vs 46.7%, P = 0.658) between patients who underwent systematic retroperitoneal lymphadenectomy and others. In addition, there was no therapeutic benefit for advanced ovarian cancer patients who underwent systematic retroperitoneal lymphadenectomy during interval debulking surgery after neoadjuvant chemotherapy [19].
Based on the results achieved in our study, no remarkable improvement was noted in survival of advanced ovarian cancer patients with optimal or suboptimal cytoreduction who underwent systematic retroperitoneal lymphadenectomy (either 2-year PFS or 5-year OS).
Panici PB et al. [12] conducted a randomized clinical trial in 2005, and randomly divided 427 patients with optimally debulked advanced ovarian cancer (stage IIIB-IV) to systematic pelvic and para-aortic lymphadenectomy group (n = 216) and resection of bulky nodes only group (n = 211). After a median follow-up of 68.4 months, the risk of recurrence was significantly lower in the systematic lymphadenectomy group (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.59–0.94; P = 0.01) than in the no-lymphadenectomy group, while the risk of death was similar in both groups (HR = 0.97, 95% CI = 0.74–1.29; P = 0.85). The majority of ovarian cancer patients treated in our hospitals had macroscopic peritoneal metastasis beyond pelvic. Thus, in the current research, we also performed a subgroup analysis of stage IIIB-IV ovarian cancer patients. Our findings indicated that lymphadenectomy had no significant effect on patients’ survival, 5-year OS rate was 77 and 78% in the lymphadenectomy group and no-lymphadenectomy group, P = 0.440; 2-year PFS was 26 and 24% in the two groups, P = 0.331.
Patients with serous ovarian cancer has a higher rate of lymph node metastasis than other types of epithelial ovarian tumors [20]. Takeshima N et al. [21] carried out an analysis of 208 ovarian cancer patients with systematic lymphadenectomy: 60 cases of serous tumor, 22 had positive lymph nodes (36.7%); 148 cases of Non-serous tumor, 25 had positive lymph nodes (16.9%). In this study, patients with serous tumor and non-serous tumor were analyzed separately. As the data showed, no matter whether the tumor was serous type or not, systematic retroperitoneal lymphadenectomy was not a prognostic factor for PFS or OS.
Lymphadenectomy in patients without clinically suspect lymph nodes and small residual disease intraperitoneally might not change the residual disease status but may reduce tumor burden that is possibly resistant to chemotherapy. In the Lymphadenectomy in Ovarian Neoplasms (LION) trial, 647 patients with newly diagnosed advanced ovarian cancer (FIGO stage IIB-IV) who had undergone macroscopically complete resection and had normal lymph nodes both before and during surgery were intraoperatively randomly assigned to lymphadenectomy and no lymphadenectomy groups. It was revealed that systematic pelvic and paraaortic lymphadenectomy in these patients was not associated with longer survival than no lymphadenectomy and was associated with a higher incidence of postoperative complications, such as incidence of lymph cysts, infection treated with antibiotics, repeat laparotomy and mortality within 60 days after surgery [11]. Similarly, in the present study, a subgroup analysis of the patients with clinically negative lymph nodes, showed that there was also no survival benefit for patients who underwent systematic lymphadenectomy.