Neoadjuvant chemotherapy followed by radical surgery versus primary surgery in stage IB2–IIB cervical adenocarcinoma: a retrospective study

This retrospective study was conducted to compare the survival outcomes of patients with cervical adenocarcinoma treated with neoadjuvant chemotherapy followed by radical surgery (NACT + RS) compared to those treated with primary surgery (PS) only. The data of stage IB2–IIB cervical adenocarcinoma patients treated with NACT + RS or PS at our institution were retrieved and assessed. Kaplan-Meier analysis was conducted to compare the survival differences between the investigated treatment groups. Cox proportional hazards model was used to identify potential prognostic factors. A total of 45 patients were eligible for this study, with 20 patients in the NACT + RS group and 25 in the PS group. The 3-year overall survival (OS) of patients from the NACT + RS group was 79.7%, while it was 84.0% for those in the PS group, but the difference was not statistically significant (p = 0.974). In addition, their corresponding 3-year progression-free survival (PFS) was also comparable, at 70.0% and 80.0%, respectively (p = 0.716). Of the responders and non-responders to neoadjuvant therapy who underwent NACT + RS, their corresponding 3-year OS was 100.0% versus 53.3% (p = 0.013), and their 3-year PFS was 90.9% versus 44.4% (p = 0.016), respectively. The incidences of lymph node metastasis, parametrial invasion, surgical margin involvement, lymphovascular space invasion and deep stromal invasion were comparable between the two treatment groups. Multivariate analysis showed that lymph node metastasis was an independent prognostic factor for PFS. In conclusion, neoadjuvant chemotherapy followed by radical surgery was not associated with improved survival prognosis or reduced pathological risk factors in patients with stage IB2–IIB cervical adenocarcinoma, but response to neoadjuvant chemotherapy could be a potential indicator of better prognosis.

Cervical adenocarcinoma; Neoadjuvant chemotherapy; Radical hysterectomy

[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–49.

[2] Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. The Lancet. 2019; 393: 169–82.

[3] Park KJ. Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification. Histopathology. 2020; 76: 112–27.

[4] Katanyoo K, Sanguanrungsirikul S, Manusirivithaya S. Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer. Gynecologic Oncology. 2012; 125: 292–296.

[5] Mabuchi S, Okazawa M, Matsuo K, Kawano M, Suzuki O, Miyatake T, et al. Impact of histological subtype on survival of patients with surgically-treated stage IA2–IIB cervical cancer: adenocarcinoma versus squamous cell carcinoma. Gynecologic Oncology. 2012; 127: 114–20.

[6] Gien LT, Beauchemin MC, Thomas G. Adenocarcinoma: a unique cervical cancer. Gynecologic Oncology. 2010; 116: 140–6.

[7] Meng Y, Chu T, Lin S, Wu P, Zhi W, Peng T, et al. Clinicopathological characteristics and prognosis of cervical cancer with different histological types: a population-based cohort study. Gynecologic Oncology. 2021; 163: 545–51.

[8] Levinson K, Beavis AL, Purdy C, Rositch AF, Viswanathan A, Wolfson AH, et al. Beyond sedlis—a novel histology-specific nomogram for predicting cervical cancer recurrence risk: an NRG/GOG ancillary analysis. Gynecologic Oncology. 2021; 162: 532–8.

[9] Cibula D, Pötter R, Planchamp F, Avall-Lundqvist E, Fischerova D, Haie Meder C, et al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients With Cervical Cancer. International Journal of Gynecological Cancer. 2018; 28: 641–55.

[10] Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri: 2021 update. International Journal of Gynecology & Obstetrics. 2021; 155: 28–44.

[11] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cervical Cancer Version 1.2022. Available at: www.NCCN.org n.d (Accessed: 01 November 2021).

[12] Wang Y, Deng L, Xu H, Zhang Y, Liang Z. Laparoscopy versus laparotomy for the management of early stage cervical cancer. BMC Cancer. 2015; 15: 928.

[13] Nam J-H, Park J-Y, Kim D-Y, Kim J-H, Kim Y-M, Kim Y-T. Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study. Annals of Oncology. 2012; 23: 903–11.

[14] Pecorino B, D’Agate MG, Scibilia G, Scollo P, Giannini A, Di Donna MC, et al. Evaluation of surgical outcomes of abdominal radical hysterectomy and total laparoscopic radical hysterectomy for cervical cancer: a retrospective analysis of data collected before the LACC Trial. International Journal of Environmental Research and Public Health. 2022; 19: 13176.

[15] Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. The New England Journal of Medicine. 2018; 379: 1895–904.

[16] Kim HS, Sardi JE, Katsumata N, Ryu HS, Nam JH, Chung HH, et al. Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-Analysis. European Journal of Surgical Oncology. 2013; 39: 115–24.

[17] Rydzewska L, Tierney J, Vale CL, Symonds PR. Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer. Cochrane Database of Systematic Reviews. 2012; 12: CD007406.

[18] Zhang Y, Li B, Wang Y, Liu S, Wang H. Paclitaxel plus platinum neoadjuvant chemotherapy followed by surgery versus primary surgery in locally advanced cervical cancer—a propensity score matching analysis. Frontiers in Oncology. 2020; 10: 604308.

[19] Yang Z, Chen D, Zhang J, Yao D, Gao K, Wang H, et al. The efficacy and safety of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer: a randomized multicenter study. Gynecologic Oncology. 2016; 141: 231–9.

[20] Gupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Sastri S, et al. Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIB squamous cervical cancer: a randomized controlled trial. Journal of Clinical Oncology. 2018; 36: 1548–55.

[21] Katsumata N, Yoshikawa H, Kobayashi H, Saito T, Kuzuya K, Nakanishi T, et al. Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs. radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan clinical oncology group trial (JCOG 0102). British Journal of Cancer. 2013; 108: 1957–63.

[22] Miriyala R, Mahantshetty U, Maheshwari A, Gupta S. Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future. International Journal of Gynecological Cancer. 2022; 32: 260–265.

[23] Ouyang P, Cai J, Gui L, Liu S, Wu N-YY, Wang J. Comparison of survival outcomes of neoadjuvant therapy and direct surgery in IB2/IIA2 cervical adenocarcinoma: a retrospective study. Archives of Gynecology and Obstetrics. 2020; 301: 1247–55.

[24] Shimada M, Nagao S, Fujiwara K, Takeshima N, Takizawa K, Shoji T, et al. Neoadjuvant chemotherapy with docetaxel and carboplatin followed by radical hysterectomy for stage IB2, IIA2, and IIB patients with non-squamous cell carcinoma of the uterine cervix. International Journal of Clinical Oncology. 2016; 21: 1128–35.

[25] Shoji T, Takatori E, Saito T, Omi H, Kagabu M, Miura F, et al. Neoadjuvant chemotherapy using platinum- and taxane-based regimens for bulky stage Ib2 to IIb non-squamous cell carcinoma of the uterine cervix. Cancer Chemotherapy and Pharmacology. 2013; 71: 657–62.

[26] GADDUCCI A, LANDONI F, COSIO S, ZIZIOLI V, ZOLA P, FERRERO AM, et al. Neoadjuvant platinum-based chemotherapy followed by radical hysterectomy for stage Ib2–IIb adenocarcinoma of the uterine cervix—an Italian multicenter retrospective study. Anticancer Research. 2018; 38: 3627–34.

[27] Querleu D, Morrow CP. Classification of radical hysterectomy. The Lancet Oncology. 2008; 9: 297–303.

[28] Mori T, Makino H, Okubo T, Fujiwara Y, Sawada M, Kuroboshi H, et al. Multi-institutional phase II study of neoadjuvant irinotecan and nedaplatin followed by radical hysterectomy and the adjuvant chemotherapy for locally advanced, bulky uterine cervical cancer: a Kansai Clinical Oncology Group study (KCOG-G1201). Journal of Obstetrics and Gynaecology Research. 2019; 45: 671–8.

[29] He L, Wu L, Su G, Wei W, Liang L, Han L, et al. The efficacy of neoadjuvant chemotherapy in different histological types of cervical cancer. Gynecologic Oncology. 2014; 134: 419–25.

[30] Ye Q, Yuan H-X, Chen H-L. Responsiveness of neoadjuvant chemotherapy before surgery predicts favorable prognosis for cervical cancer patients: a meta-analysis. Journal of Cancer Research and Clinical Oncology. 2013; 139: 1887–98.

[31] Kong S, Huang K, Zeng C, Ma X, Wang S. The association between short-term response and long-term survival for cervical cancer patients undergoing neoadjuvant chemotherapy: a system review and meta-analysis. Scientific Reports. 2018; 8: 1545.

[32] Huang Y, Liu L, Cai J, Yang L, Sun S, Zhao J, et al. The efficacy and response predictors of platinum-based neoadjuvant chemotherapy in locally advanced cervical cancer. Cancer Management and Research. 2020; 12: 10469–77.

[33] Li P, Fang Z, Li W, Hao M, Wang W, Kang S, et al. Impact of neoadjuvant chemotherapy on the postoperative pathology of locally advanced cervical squamous cell carcinomas: 1:1 propensity score matching analysis. European Journal of Surgical Oncology. 2021; 47: 1069–74.

[34] Bogani G, Donato V Di, Scambia G, Landoni F, Ghezzi F, Muzii L, et al. Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer. Gynecologic Oncology. 2022; 166: 561–6.

[35] Fader AN. Surgery in cervical cancer. The New England Journal of Medicine. 2018; 379: 1955–7.

[36] Yuan P, Liu Z, Qi J, Yang X, Hu T, Tan H. Laparoscopic radical hysterectomy with enclosed colpotomy and without the use of uterine manipulator for early-stage cervical cancer. Journal of Minimally Invasive Gynecology. 2019; 26: 1193–8.