Number of lymph node in early-stage cervical cancer after radical surgery, does it matter?

Objective: To determine the number of lymph nodes obtained from radical hysterectomy with pelvic lymphadenectomy (RHPL) and survival rates of the early-stage cervical cancer patients with various numbers of removed lymph nodes (RLNs) and metastatic lymph nodes (MLNs). Materials and methods: 407 patients with early-stage cervical cancers who underwent RHPL were included in this study. We reviewed all medical records from January 2005–June 2020 and excluded the patients who had incomplete medical record, loss of follow-up visits and received neo-adjuvant chemotherapy. Results: Three-hundred-and-fifty-four patients were analyzed. The median time of follow-up was 44.3 months, the average number of RLNs was 23 (range 7–29) and 91.7% of our cases had >12 RLNs. MLNs were found in 36 cases (10.2%). The patients with RLNs <12 had a significantly lower 5-year cancer-specific survival (CSS) compared to those with RLNs $>$12 (73.6 % and 97.0%, respectively, p-value < 0.001) but 5-year progression-free survival (PFS) was not different between both groups. Based on lymph node status, the 5-year PFS and CSS of node-negative vs. node-positive patients were 99.3% vs. 76.2% and 97.5% vs. 74.0%, respectively. Conclusion: An extensive lymphadenectomy had a survival benefit in early-stage cervical cancer patients. The patients with RLNs >12 had better 5-year CSS. MLNs and RLNs $<$12 are significant prognostic factors for PFS and CSS.

Early-stage cervical cancer; Lymphadenectomy; Number of lymph node; Survival outcome

[1] International Agency for Research on Cancer. Population fact sheets. 2018. Available at: https://gco.iarc.fr/today/data/factshe ets/cancers/23-Cervix-uteri-fact-sheet.pdf (Accessed: 24 August 2020).

[2] Imsamran W. 2018 Cancer incidence in Thailand: cervical cancer. Cancer in Thailand. 2018; IV: 77.

[3] Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. International Journal of Gynecology & Obstetrics. 2018; 143: 22–36.

[4] Liu Y, Ni L, Wang S, Lv Q, Chen W, Ying S. Outcome and prognostic factors in cervical cancer patients treated with surgery and concurrent chemoradiotherapy: a retrospective study. World Journal of Surgical Oncology. 2018; 16: 18.

[5] Yan D, Tang Q, Chen J, Tu Y, Lv X. Prognostic value of the 2018 FIGO staging system for cervical cancer patients with surgical risk factors. Cancer Management and Research. 2019; 11: 5473–5480.

[6] Li D, Xu X, Yan D, Yuan S, Ni J, Lou H. Prognostic factors affecting survival and recurrence in patients with early cervical squa- mous cell cancer following radical hysterectomy. Journal of Inter- national Medical Research. 2020; 48: 030006051988974.

[7] Thanabhinunt P, Nakariyakul B, Wasinghon P. Prognostic factors and survival rates in early-stage cervical p Treated with Radical Hysterectomy and Pelvic Lymphadenectomy. Thai Journal of Ob- stetrics and Gynaecology October. 2018; 26: 270–281.

[8] Shah M, Lewin SN, Deutsch I, Burke WM, Sun X, Herzog TJ, et al. Therapeutic role of lymphadenectomy for cervical cancer. Cancer. 2011; 117: 310–317.

[9] Mao S, Dong J, Li S, Wang Y, Wu P. Prognostic significance of number of nodes removed in patients with node-negative early cervical cancer. Journal of Obstetrics and Gynaecology Research. 2016; 42: 1317–1325.

[10] Verleye L, Vergote I, Reed N, Ottevanger PB. Quality assurance for radical hysterectomy for cervical cancer: the view of the Eu- ropean Organization for Research and Treatment of Cancer— Gynecological Cancer Group (EORTC-GCG) Annals of Oncol- ogy. 2009; 20: 1631–1638.

[11] Peters WA, Liu PY, Barrett RJ, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radi- cal surgery in high-risk early-stage cancer of the cervix. Journal of Clinical Oncology. 2000; 18: 1606–1613.

[12] Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no fur- ther therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: a Gynecologic Oncology Group Study. Gynecologic Oncology. 1999; 73: 177–183.

[13] Suprasert P, Charoenkwan K, Khunamornpong S. Pelvic node removal and disease-free survival in cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy. Interna- tional Journal of Gynaecology and Obstetrics. 2012; 116: 43–46.

[14] Pieterse QD, Kenter GG, Gaarenstroom KN, Peters AAW, Willems SM, Fleuren GJ, et al. The number of pelvic lymph nodes in the quality control and prognosis of radical hysterectomy for the treatment of cervical cancer. European Journal of Surgical Oncology. 2007; 33: 216–221.

[15] Wang R, Tao X, Wu X, Jiang H, Xia H. Number of Removed Pelvic Lymph Nodes as a Prognostic Marker in FIGO Stage IB1 Cervical Cancer with Negative Lymph Nodes. Journal of Minimally Invasive Gynecology. 2020; 27: 946–952.

[16] Ditto A, Martinelli F, Lo Vullo S, Reato C, Solima E, Carcangiu M, et al. The role of lymphadenectomy in cervical cancer patients: the significance of the number and the status of lymph nodes removed in 526 cases treated in a single institution. Annals of Surgical On- cology. 2013; 20: 3948–3954.

[17] Bogani G, Vinti D, Murgia F, Chiappa V, Leone Roberti Maggiore U, Martinelli F, et al. Burden of lymphatic disease predicts efficacy of adjuvant radiation and chemotherapy in FIGO 2018 stage II-ICp cervical cancer. International Journal of Gynecologic Cancer. 2019; 29: 1355–1360.

[18] Zeng J, Qu P, Hu Y, Sun P, Qi J, Zhao G, et al. Clinicopathological risk factors in the light of the revised 2018 International Federa- tion of Gynecology and Obstetrics staging system for early cervical cancer with staging IB. Medicine. 2020; 99: e19714.

[19] Nanthamongkolkul K, Hanprasertpong J. Predictive Factors of Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer. Oncology Research and Treatment. 2018; 41: 194–198.

[20] Bona AF, Ferreira KR, Carvalho RBDM, Thuler LCS, Bergmann A. Incidence, prevalence, and factors associated with lymphedema after treatment for cervical cancer: a systematic review. Interna- tional Journal of Gynecologic Cancer. 2020; 30: 1697–1704.

[21] Kadkhodayan S, Hasanzadeh M, Treglia G, Azad A, Yousefi Z, Zarifmahmoudi L, et al. Sentinel node biopsy for lymph nodal staging of uterine cervix cancer: a systematic review and meta-analysis of the pertinent literature. European Journal of Surgical Oncology. 2015; 41: 1–20.

[22] Salvo G, Ramirez PT, Levenback CF, Munsell MF, Euscher ED, Soliman PT, et al. Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer. Gynecologic Oncology. 2017; 145: 96–101.

[23] Lennox GK, Covens A. Can sentinel lymph node biopsy replace pelvic lymphadenectomy for early cervical cancer? Gynecologic Oncology. 2017; 144: 16–20.