Radical hysterectomy and bilateral pelvic lymphadenectomy are still the primary clinical treatment methods for patients with early-stage cervical cancer. PLNM is the main metastatic route of cancer cell proliferation and an essential determinant of prognosis [8, 9]. The incidence of PLNM after cervical cancer surgery has been reported to range from 15 to 30% in patients with Stage IA–IIA cervical cancer. [6, 7]. In this study, the incidence of PLNM was 24%. The clinicopathologic data from 245 patients with FIGO IA-IIA cervical cancer treated by radical surgery were retrospectively analyzed. It was found that preoperative hemoglobin <110 g/L, FIGO stage II, LVSI, parametrial infiltration, and tumor diameter ≥4 cm as significant risk factors for PLNM and recurrence of cervical cancer after surgery.
The hemoglobin level reduces commonly in the perioperative period [10]. Moreover, anemia occurs in more than one-third of cancer patients, and severe anemia is a risk factor for death in such patients [11–13]. The level of hemoglobin, the primary oxygen carrier, directly affects the oxygen supply and oxygen content of the tumor. Preoperative blood transfusion and other strategies do not improve prognosis in cervical cancer patients, and in patients complicated with anemia, the tumor is highly aggressive, further deteriorating the prognosis [14, 15]. In this study, the number of patients with preoperative hemoglobin <110 g/L was significantly higher in the PLNM(+) group than in PLNM(-) group(P<0.02).And the number of patients with preoperative hemoglobin <110 g/L was significantly higher in the recurrence groups than in the no-recurrence groups(P<0.03). Moreover, preoperative hemoglobin <110 g/L was identified as an independent risk factor for postoperative PLNM and recurrence of cervical cancer after surgery. This finding was consistent with the results of previous studies.
Tumor staging is a defining index of tumor growth and the extent of its spread. As the tumor stage increases, the depth and extent of tumor invasion to the surrounding tissue, the aggressiveness and malignancy of the tumor, and the recurrence rate increase significantly [3, 16]. PLNM rates of Ia, Ib, IIa, and IIb stages are reported to be 10.5%,13.1%, 27.1%, and 50.0%, respectively [17], confirming that LNM increases with advanced FIGO stages. In this study, the number of FIGO stage II cervical cancer patients with PLNM was higher than the number of FIGO stage I cervical cancer patients with PLNM (P=0.005). This finding is consistent with previously reported results.
LVSI, deep stromal invasion, parametrial infiltration, and tumor diameter are closely related to PLNM and the recurrence of early cervical cancer [18, 19]. LVSI is pathologically confirmed by the presence of malignant tumor cells between two layers of vascular endothelial tissue and is an important prognostic index of cervical cancer. Vascular infiltration is an independent risk factor for PLNM [20, 21]. When cancer cells invade the lymphatic space, they can promote the formation of tumor thrombosis and invade local lymph nodes through the lymphatic vessels, thus inducing parametrial infiltration and PLMN [22, 23]. Consistent with previous studies, in our study, the proportions of patients with LVSI (81.67%) and parametrial infiltration (75%) in the PLNM(+) group were significantly higher than those of patients in the PLNM(-) group (P<0.005).
The tumor diameter can reflect the tumor growth time as tumor growth is a continuous invasion and proliferation process. The longer the growth time, the more likely is the lymph node metastasis [6, 7]. With an increase in tumor diameter and a prolonged growth period, the depth of stromal invasion tends to increase. The contact area between tumor tissue and lymphatic vessels and the risk of LNM also tend to significantly increase [18, 24, 25]. A study on the prognosis of 93 patients with early cervical cancer after surgery found that a tumor diameter ≥4 cm is a risk factor for PLNM and recurrence of cervical cancer [26]. In this study, the number of patients with tumor diameter ≥4 cm and deep stromal invasion differed significantly between the two groups (P<0.005 and P<0.05), consistent with previous studies.
Besides preoperative hemoglobin <110 g/L, LVSI, deep stromal invasion, parametrial infiltration, and tumor diameter ≥4 cm, it was shown that PLNM is an independent risk factor for the recurrence of cervical cancer. PLNM is more likely to occur in advanced cervical cancer. Postoperative invasion, metastasis, and recurrence are prone to occur in patients with PLNM[21, 23]. Thus, the postoperative survival rate tends to decrease [27, 28]. Pelvic lymph node dissection can effectively remove metastatic lymph nodes, reduce the tumor load, prevent PLNM, and reduce the risk of distant recurrence [29, 30]. For patients with positive pelvic lymph nodes, the interval between recurrence is significantly shorter than for those with negative lymph nodes, and the risk of recurrence is relatively higher [6]. In this study, the proportion of patients with PLNM in the recurrence group was (79.47%) significantly higher than that in the non-recurrence group (P=0.000). PLNM was therefore identified as an independent risk factor for recurrence in patients with cervical cancer after radical hysterectomy and bilateral pelvic lymphadenectomy.
The main strength of this study was that patients with recurrence after surgery were from the same group of patients with PLNM, thereby reducing bias and achieving more accurate results.
This study also has unavoidable limitations due to its retrospective design. First, we could not assess all variables potentially associated with residual lesions in this single-center study. Furthermore, because the study population was from one hospital, the external validity of our results may be low. Further prospective studies with a larger sample size and a broader context are needed.