Region-specific Risk Factors for Pelvic Lymph Node Metastasis in Patients with Stage IB1 Cervical Cancer

Abstract

Objectives: We aimed to identify the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location in patients with stage IB1 cervical cancer. Methods: A primary cohort of 728 patients with stage IB1 cervical cancer who underwent radical hysterectomy and systematic pelvic lymphadenectomy were retrospectively studied. All removed pelvic nodes (N=20,134) were pathologically examined. The risk factors for LNM in different anatomic regions (obturator, internal iliac, external iliac, and common iliac) were evaluated by multivariate logistic regression analyses. Nomograms were generated from the primary cohort and validated in another external cohort (N=242). The performance of the nomogram was assessed by its calibration and discrimination. Overall survival and progression-free survival in patients with different LNM patterns were compared. Results: LNM was found in 266 (1.3%) removed nodes and 106 (14.6%) patients. The incidences of LNM at the obturator, internal iliac, external iliac, common iliac, and parametrial regions were 8.5%, 5.4%, 4.7%, 1.9% and 1.8%, respectively. Among others, tumour size and lymph-vascular space invasion (LVSI), which are preoperatively assessable, were identified as independent risk factors of LNM in the common iliac region and the lower pelvis, respectively, and age was an additional independent risk factor of obturator LNM. The negative predictive values of tumour size <2 cm for common iliac LNM and negative LVSI combined with older age (> 50 years) for obturator LNM were 100% and 98.7%, respectively. A nomogram of these two factors showed good calibration and discrimination (concordance index, 0.761 in the primary cohort and 0.830 in validation cohort). The patients with common iliac LNM had poorer survival than those with LNM confined to the lower pelvis, while the differences in survival between patients with LNM confined to one node, one region or single side and those with more widely spreading LNM were not statistically significant. Conclusions: Tumour size, LVSI and age are region-specific risk factors for pelvic LNM in IB1 cervical cancer, which could be used to allocate the appropriate extent of pelvic lymphadenectomy.

Keywords: cervical cancer; early stage.; lymph node metastasis; lymphadenectomy.

Figure 1

The incidence and distribution of pelvic lymph node metastasis in patients with stage IB1 cervical cancer. (A) Distribution of the 266 positive lymph nodes. (B) Venn diagram showing the number of patients with lymph node metastasis in different regions. (C) The incidence of pelvic lymph node metastasis at individual anatomic regions in 728 patients.

Figure 2

Kaplan-Meier analysis of survival for IB1 cervical cancer patients. (A) Progression-free survival based on the status of lymph nodes. (B) Overall survival based on the status of lymph nodes. (C) Progression-free survival stratified by LNM anatomic regions. (D) Overall survival stratified by LNM anatomic regions. (E) Progression-free survival stratified by unilateral and bilateral LNM. (F) Overall survival stratified by unilateral and bilateral LNM. (G) Progression-free survival based on the number of positive lymph nodes. (H) Overall survival based on the number of positive lymph nodes. (I) Progression-free survival based on the number of regions of LNM. (J) Overall survival based on the number of regions of LNM.

Figure 3

Development and performance of the nomogram C for obturator lymph node metastasis. (A) The nomogram C was developed in the model development cohort, with lymph-vascular space invasion and age. (B, C) Calibration curves of the nomogram C in the model development cohort (B) and validation cohorts (C). (D, E) ROC plots of the nomogram in the model development cohort (D, AUC=0.761, 95% CI=0.699-0.823) and validation cohorts (E, AUC=0.830, 95% CI=0.743-0.918)