Could the Extent of Lymphadenectomy Be Modified by Neoadjuvant Chemotherapy in Cervical Cancer? A Large-Scale Retrospective Study

<div><p>Background</p><p>The effect of neoadjuvant chemotherapy (NACT) on topographical distribution patterns of lymph node metastasis in cervical cancer was unknown.</p><p>Methods</p><p>Patients with FIGO stage IB1-IIB who underwent radical surgery with or without NACT were enrolled (3527 patients). A matched-case comparison design was used to compare the effects of NACT on lymph node metastasis.</p><p>Results</p><p>We analyzed groups of 167 and 140 patients who were diagnosed with lymph node metastasis in the matched primary surgery group and NACT group, respectively, and no significant difference was observed (p = 0.081). The incidence of lymph node metastasis was significantly decreased in the NACT-responsive group compared to the non-responsive group (18.4% vs. 38.6%, P<0.001). The metastatic rates for every lymph node group also declined in the NACT-responsive group except for the deep inguinal and the para-aortic lymph node groups. Clinical response, deep stromal, parametrial and lymph vascular invasions were independent risk factors for lymph node metastasis in the NACT group. Furthermore, deep stromal invasion and lymph vascular invasion, but not the response to NACT, were independently associated with upper LNM. The number of lymph nodes involved, response to NACT, tumor histology and a positive vaginal margin were independent prognostic factors affecting DFS or OS rates in node-positive patients treated with NACT plus radical surgery.</p><p>Conclusion</p><p>The frequency and topographic distribution of LNM are not modified by NACT, and clinical non-responders showed more involved LNs. A systemic and extensive lymphadenectomy should be performed in patients treated with NACT plus surgery regardless of the response to NACT.</p></div

Overall survival and disease-free survival of patients in the primary NACT group by the site of lymph nodes involved.

<p>(A-B) negative lymph nodes, lower and upper positive lymph nodes; (C-D) negative lymph nodes, unilateral and bilateral positive lymph nodes.</p

Univariate and multivariate analysis for lymph node metastases and deep stromal infiltration.

<p>FIGO, International Federation of Gynecology and Obstetrics; NACT, neoadjuvant chemotherapy; SCC-Ag, squamous cell carcinoma antigen.</p><p>^a<i>P</i> value calculated using fisher's exact test.</p><p>Univariate and multivariate analysis for lymph node metastases and deep stromal infiltration.</p

Multivariate analyses of risk factors for lymph node metastasis and upper lymph node metastasis in patients who had received NACT.

<p>Multivariate analyses of risk factors for lymph node metastasis and upper lymph node metastasis in patients who had received NACT.</p

Univariate and multivariate analysis for disease-free survival and overall survival.

<p>DFS, disease-free survival; OS, overall survival; FIGO, International Federation of Gynecology and Obstetrics; NACT, neoadjuvant chemotherapy.</p><p>Univariate and multivariate analysis for disease-free survival and overall survival.</p

Comparison of incidence of LNM between matched NACT group and PST group, primary NACT group with clinical response and with clinical non-response, respectively, stratified by tumor size, FIGO stage, and histology.

<p>Comparison of incidence of LNM between matched NACT group and PST group, primary NACT group with clinical response and with clinical non-response, respectively, stratified by tumor size, FIGO stage, and histology.</p

Univariate and multivariate analysis for clinical response of neoadjuvant chemotherapy.

<p>CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; FIGO, International Federation of Gynecology and Obstetrics; NACT, neoadjuvant chemotherapy; SCC-Ag, squamous cell carcinoma antigen.</p><p>^a<i>P</i> value calculated using fisher's exact test.</p><p>Univariate and multivariate analysis for clinical response of neoadjuvant chemotherapy.</p

Demographic characteristics of women of different willingness towards cervical cancer screening (n = 5929) (From χ² test).

<p>Demographic characteristics of women of different willingness towards cervical cancer screening (n = 5929) (From χ² test).</p

Overall survival and disease-free survival of patients in the primary NACT group by the number of lymph nodes involved (A, B) and the number of lymph node groups involved (C, D).

<p>Overall survival and disease-free survival of patients in the primary NACT group by the number of lymph nodes involved (A, B) and the number of lymph node groups involved (C, D).</p

Overall survival and disease-free survival compared among patients of different subgroups.

<p>(A-B): The comparison of OS and DFS among the young responders subgroup, young non-responders subgroup, older responders subgroup, and older non-responders subgroup. (C-D): The comparison of OS and DFS among the young responders subgroup, young non-responders subgroup, older responders subgroup, and older non-responders subgroup among patients with FIGO stage IB1-IB2 disease. (E-F): The comparison of OS and DFS among the young responders subgroup, young non-responders subgroup, older responders subgroup, and older non-responders subgroup among patients with FIGO stage IIA-IIB disease.</p