Clinical significance of para-aortic lymph node dissection and prognosis in ovarian cancer

Abstract

Lymph node metastasis has an important effect on prognosis of patients with ovarian cancer. Moreover, the impact of para-aortic lymph node (PAN) removal on patient prognosis is still unclear. In this study, 80 patients were divided into groups A and B. Group A consisted of 30 patients who underwent PAN+ pelvic lymph node (PLN) dissection, whereas group B consisted of 50 patients who only underwent PLN dissection. Analysis of the correlation between PAN clearance and prognosis in epithelial ovarian cancer was conducted. Nineteen cases of lymph node metastasis were found in group A, among whom seven cases were positive for PAN, three cases for PLN, and nine cases for both PAN and PLN. In group B, 13 cases were positive for lymph node metastasis. Our study suggested that the metastatic rate of lymph node is 40.0%. Lymph node metastasis was significantly correlated with FIGO stage, tumor differentiation, and histological type both in groups A and B (P<0.05). In groups A and B, the three-year survival rates were 77.9% and 69.0%, and the five-year survival rates were 46.7% and 39.2%, respectively. However, the difference was not statistically significant (P>0.05). The three-year survival rates of PLN metastasis in groups A and B were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%, respectively. Furthermore, PLN-positive patients who cleared PAN had significantly higher survival rate (P=0.044). In group A, the three-year survival rates of positive and negative lymph nodes were 43.5% and 72.7%, and the five-year survival rates were 27.2% and 58.5%, respectively. The difference was statistically significant (P=0.048). Cox model analysis of single factor suggested that lymph node status affected the survival rate (P<0.01), which was the death risk factor. Consequently, in ovarian carcinoma cytoreductive surgery, resection of the para-aortic lymph node, which has an important function in clinical treatment and prognosis of patients with ovarian cancer, is necessary.

Keywords

ovarian cancer / para-aortic lymph node / pelvic lymph node

Introduction

Ovarian cancer is a serious threat to women’s health and life. It spreads easily, implants directly in the peritoneum, and has poor prognosis. The mortality rate of ovarian cancer ranks first in gynecological malignant tumor. The current five-year survival rate in patients with ovarian cancer is still stranded from 19% to 40% [1,2]. Lymph node metastasis is one of the most critical prognostic factors of ovarian cancer. Several authors have studied the therapeutic role of lymph node adenectomy, focusing mainly on pelvic lymph node (PLN) adenectomy in patients with ovarian cancer [3,4]. The diagnostic importance of para-aortic lymph node (PAN) adenectomy has been established, but conclusive studies on the therapeutic relevance of PAN are still lacking. Improvement of the survival rate and prognosis through clearing of the para-aortic lymph nodes in ovarian carcinoma cytoreductive surgery is still debatable. In this study, 80 patients with primary epithelial ovarian cancer were divided into two groups according to performance of sweeping para-aortic lymph nodes to assess postoperative survival situation of patients.

Materials and methods

Clinical information

Eighty ovarian cancer patients who received ovarian cancer cytoreductive surgery from 2006 to 2010 were from Xiangyang Central Hospital. All patients received system pelvic lymphadenectomy, including 11 cases of intermediate cytoreductive surgery. The 80 patients were divided into groups A and B, wherein group A consisted of 30 patients who underwent PAN+ PLN clearance surgery and group B consisted of 50 patients who underwent only PLN clearance surgery. The serum cancer antigen (CA125) concentration was examined in our laboratory department 2 to 7 days before operation. The patients were aged 22 years to 75 years (average of 52 years). Conditions of the patients were classified through FIGO staging as follows: 15 cases of stage I, 13 cases of stage II, 44 cases of stage III, and 8 cases of stage IV. Tumor cells were differentiated as follows: 15 cases of G1, 22 cases of G2, and 43 cases of G3. The histological types according to World Health Organization (1973) classification were 50 cases of serous tumors, 9 cases of mucus tumors, 9 cases of clear cell renal tumors, 10 cases of endometrial tumors, and 2 cases of unclassified carcinoma. The diameters of the tumors were less than 10 cm in 53 cases and equal to or greater than 10 cm in 27 cases. In serum CA125 levels, 9 cases were<50 IU/ml, 31 cases were 50 IU/ml to 500 IU/ml, and 40 cases were≥500 IU/ml. No significant difference was observed for age, FIGO stage, pathological grade, primary tumor size, histological type, and level of serum CA125 in the two groups, as shown in Table 1.

Follow-up

All 80 cases were followed up periodically. Survival was calculated from the day of cytoreductive surgery to either the day of death or June 30, 2013. The median follow-up time was 25.4 months. The duration was 60 months. The follow-up rate was 88.75% because nine patients were unable to establish connection. The follow-up data of some patients were recorded during postoperative examination in our hospital, including physical and pelvic check-up, B-ultrasound, CT or MRI examination, blood CA125 and CA199 test. The rest were followed up by telephone or letter.

Statistical analysis

Statistical analysis was performed using SPSS 16.0 software (SPSS Inc., Chicago, IL, USA). Chi-square was used to analyze the associations between lymph node status and clinical-pathological characteristics. The Kaplan-Meier method was applied for survival, and the log-rank test was used to analyze statistical significance in the two groups. For all tests, a P-value<0.05 was considered significant.

Results

Lymph node status and related clinical-pathological factors

In group A, 19 patients had lymph node metastasis. Among these 19 patients, seven were positive for PAN, three were positive for PLN, and nine were positive for PAN and PLN. In group B, 13 patients had PLN metastases. A total of 32 among the 80 cases had retroperitoneal lymph node metastasis. Metastasis rate was 40%. PAN metastasis was observed in 16 cases (20.0%), and PLN in 25 cases (31.3%). Lymph node metastasis was not significantly correlated with age, tumor size, and level of serum CA125 in groups A and B (P>0.05). In group A, the lymph node metastasis rate in FIGO stages I and II, III, and IV were 0.0%, 34.1%, and 50.0% respectively; G1, G2, and G3 were 6.7%, 13.6%, and 34.9%, respectively. Histological types or serous tumors and non-serous tumors were 36% and 3.3%, respectively, with significant difference (P = 0.017, 0.015, and 0.047, respectively). In group B, positive lymph node rates in FIGO stages I and II, III, and IV were 0.0%, 25.0%, and 25.0%, respectively; G1, G2, and G3 were 0.0%, 13.6%, and 23.3%, respectively. Histological types or serous tumors and non-serous tumors were 20.0% and 10.0%, respectively, with significant difference (P = 0.001, 0.042, and 0.025, respectively). Lymph node metastasis was significantly correlated with FIGO stage, tumor differentiation, and histological type in groups A and B, as shown in Table 1.

Distribution of lymph node metastasis

The number of clear lymph nodes was 12 to 36, with an average of 23. The number of positive lymph nodes was 1 to 12, and the median was 3.3. In group A, 16 cases of PAN transfer and 12 cases of PLN metastasis were observed. Sixteen cases of lymph node metastatic sites to PAN were observed in group A, including left side in 2 cases, right side in 8 cases, and bilateral in 6 cases, followed by internal iliac, closed holes, common iliac, external iliac and inguinal lymph nodes. However, the overall difference was not statistically significant (P>0.05) as shown in Table 2.

Comparison of survival rates between groups A and B

Table 3 demonstrates 77.9% three-year survival rate in group A and 69.0% three-year survival rate in group B, as well as 46.7% five-year survival rate in group A and 39.2% five-year survival rate in group B. The survival rate of patients with PAN removal in group A was higher than that of the uncleared in group B. However, the difference between the two groups was not statistically significant (P = 0.976).

Correlation between lymph nodes status and survival rates in groups A and B

With retroperitoneal lymph node involved in different ranges, with or without removal of para-aortic lymph nodes, the survival rates of the patients were different. In groups A and B, the three-year survival rates without lymph node metastasis were 79.2% and 73.3%, and the five-year survival rates were 70.4% and 59.5%, respectively. No significant difference was observed between the two groups (P>0.05). However, a significant difference (P<0.05) was observed between the survival rates of patients with PLN or PAN transfer and patients without lymph node metastasis. By contrast, the survival rate did not exhibit significant difference between PLN metastasis and PAN invasion of patients (P>0.05). Interestingly, the three-year survival rates in groups A and B which transferred to PLN were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%. The difference was statistically significant (P = 0.044), indicating that PLN-positive patients underwent clearance of PAN with higher survival rates than uncleared PAN patients. Moreover, in group A, the three-year survival rates in patients with positive and negative lymph nodes were 43.5% and 72.7%, respectively. The five-year survival rates were 27.2% and 58.5%, respectively, with statistically significant difference (P = 0.048). In addition, Cox model analysis of single factor suggested that lymph node status affected survival rate (P <0.01), which was the death risk factor. The ratios between lymph node metastasis and without lymph node metastasis were compared to 2.73 (Table 4).

Discussion

With the development of retroperitoneal lymph node dissection in the treatment of ovarian cancer, more attention is directed toward lymph node status influence on survival time of patients. However, the mechanism through which para-aortic lymph node dissection affects the survival rate of patients with ovarian cancer remains poorly understood. In our study, the results revealed that the three- and five-year survival rates in patients with PAN removal were higher than those without PAN. No significant difference was observed between groups A and B (P>0.05). However, the three-year survival rates of PLN metastasis in groups A and B were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%, respectively, indicating that PLN-positive patients who cleared PAN had significantly higher survival rates (P = 0.044). Furthermore, in group A, the three-year survival rates in patients with positive and negative lymph nodes were 43.5% and 72.7%. The five-year survival rates were 27.2% and 58.5%, respectively, with statistically significant difference (P = 0.048). In addition, Cox model analysis of single factor suggested that lymph node status affected the survival rate (P<0.01), which was the death risk factor. Therefore, preliminary results suggest that PLN-positive patients who received pelvic lymph node and para-aortic lymph node dissection have significantly higher survival rate than patients without para-aortic lymph node elimination. In the removal of PAN, patients with positive lymph node had lower survival rates. Moreover, resection of para-aortic lymph nodes and lymph node metastasis may be an independent prognostic factor in ovarian cancer, which should be implemented.

Lymph node metastasis is one of the main modes of transmission of ovarian cancer, especially pelvic and aortic lymph nodes; the metastasis rate is generally 20% to 69.4% [5]. Ovarian cancer lymph node metastasis occurs as follows: along the infundibulopelvic ligament to the para-aortic lymph nodes, through the broad ligament transferred to the internal iliac, external iliac, and closed-hole lymph nodes, and metastasis to inguinal lymph nodes by the round ligament. The present data showed that removal of six groups of lymph nodes was undertaken in lymph node metastatic sites to PAN in up to 16 cases in group A, followed by internal iliac, closed holes, common iliac, external iliac, and inguinal lymph nodes. However, the overall difference was not statistically significant, as shown in Table 2.

Lower differentiation of ovarian cancer cells, higher degree of malignancy with stronger invasion force of tumor, and increased lymph node metastasis rate were observed [6]. The results from Table 1 suggest that lymph node metastasis was significantly correlated with tumor differentiation and histological type. In conclusion, poorly differentiated cancer and serous adenocarcinoma were both high risk factors of lymph node metastasis in ovarian cancer [6,7]. Moreover, metastasis rates were increased in the stage of FIGO in groups A and B. PAN metastasis was associated with clinical stage, and the difference was statistically significant (P = 0.017 and 0.001, respectively). Therefore, removal of the para-aortic and pelvic lymph nodes is essential [6,8].

Most scholars have posited that chemotherapy has no effect on lymph node metastasis in retroperitoneal of gynecologic malignant tumors [9,10]. The main reason for this phenomenon is the systemic or intraperitoneal administration of drug dosage, which rarely reaches the area of retroperitoneal lymph node. Consequently, the drug cannot take effect. Therefore, para-aortic and pelvic lymphadenectomy therapy to improve the prognosis of patients with ovarian cancer is particularly important. Polverino [11] believed that only resection of para-aortic and pelvic lymph nodes can treat lymph node metastasis of ovarian cancer patients. In summary, in ovarian carcinoma cytoreductive surgery, para-aortic lymph nodes have an important function in the clinical treatment and prognosis improvement of patients with ovarian cancer; thus, they should be resectioned.

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