Comparison of pathological outcomes of neoadjuvant chemotherapy before surgery versus radical hysterectomy alone in stage IB3 and IIA2 cervical cancer

As an alternative treatment strategy, the efficacy of neoadjuvant chemotherapy (NAC) for patients with stage IB3 and IIA2 cervical carcinoma remains uncertain. To address this limitation, this evaluates the pathological outcomes of patients with locally advanced cervical cancer (LACC) treated with NAC before surgery compared with those who underwent radical hysterectomy (RH) alone. A total of 592 patients with stage IB3 and IIA2 cervical cancer were eligible for this study. They were divided into a NAC group (NAC before surgery, n = 259) and a RH group (radical hysterectomy alone, n = 333). Propensity score matching (PSM) was used to eliminate confounding intergroup factors, leading to 233 cases being finally included in the two groups. Patients in the NAC group received 1–3 cycles of nedaplatin plus paclitaxel/docetaxel/irinotecan regimens, followed by surgery 3–5 weeks post-NAC. Patients in the RH group underwent radical hysterectomy after the diagnosis of cervical cancer. Intermediate-risk factors (i.e., lymphovascular space invasion and deep stromal infiltration) and high-risk factors (i.e., lymph node metastasis, positive parametria and positive surgical margin) for the recurrence of LACC were compared between the two groups before and after PSM. The results showed no significant difference in high-risk factors between the NAC and RH groups before and after PSM (p > 0.05). In regard to intermediate-risk factors, a significant difference was observed before PSM in inter-group analysis (lymphovascular space invasion, p = 0.028; deep stromal infiltration, p = 0.011). After PSM, only deep stromal infiltration remained significant, with a decreased incidence observed in the NAC group (p = 0.004). In conclusion, NAC before surgery had minimal impact on high-risk factors and lymphovascular space invasion compared to the RH group. However, we did observe a decrease in deep one-third stromal invasion. These results may be relevant to the decision-making process for postoperative radiotherapy.

Uterine cervical neoplasms; Risk factors; Neoadjuvant therapy; Hysterectomy

[1] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: A Cancer Journal for Clinicians. 2022; 72: 7–33.

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

[3] Phillips P, Phillips J. Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer. Clinical Nurse Specialist. 2017; 31: 189–190.

[4] Rose PG. Locally advanced cervical cancer. Current Opinion in Obstetrics and Gynecology. 2001; 13: 65–70.

[5] Akhavan S, Alibakhshi A, Parsapoor M, Alipour A, Rezayof E. Com-parison of therapeutic effects of chemo-radiotherapy with neoadjuvant chemotherapy before radical surgery in patients with bulky cervical carcinoma (stage IB3 & IIA2). BMC Cancer. 2021; 21: 667.

[6] Chen B, Wang L, Ren C, Shen H, Ding W, Zhu D, et al. The effect of neoadjuvant chemotherapy on lymph node metastasis of FIGO Stage IB1–IIB cervical cancer: a systematic review and meta-analysis. Frontiers in Oncology. 2020; 10: 570258.

[7] Napolitano U, Imperato F, Mossa B, Framarino ML, Marziani R, Marzetti L. The role of neoadjuvant chemotherapy for squamous cell cervical cancer (Ib–IIIb): a long-term randomized trial. European Journal of Gynaecological Oncology. 2003; 24: 51–59.

[8] 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.

[9] Qin T, Zhen J, Zhou M, Wu H, Ren R, Qu B, et al. Efficacy of neoadjuvant chemotherapy plus radical surgery in patients with bulky stage II cervical squamous cell carcinoma: a retrospective cohort study. International Journal of Surgery. 2016; 30: 121–125.

[10] Gupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Sastri Chopra 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: 1548–1555.

[11] Zhao H, He Y, Yang SL, Zhao Q, Wu YM. Neoadjuvant chemotherapy with radical surgery vs. radical surgery alone for cervical cancer: a systematic review and meta-analysis. OncoTargets and Therapy. 2019; 12: 1881–1891.

[12] Yan W, Si L, Ding Y, Qiu S, Zhang Q, Liu L. Neoadjuvant chemotherapy does not improve the prognosis and lymph node metastasis rate of locally advanced cervical squamous cell carcinoma. Medicine. 2019; 98: e17234.

[13] Mousavi A, Modarres Gilani M, Akhavan S, Sheikh Hasani S, Alipour A, Gholami H. The outcome of locally advanced cervical cancer in patients treated with neoadjuvant chemotherapy followed by radical hysterectomy and primary surgery. Iranian Journal of Medical Sciences. 2021; 46: 355–363.

[14] Dang Y, Liu Q, Long L, Luan H, Shi Q, Tuo X, et al. The effect of neoadjuvant chemotherapy combined with brachytherapy before radical hysterectomy on stage IB2 and IIA cervical cancer: a retrospective analysis. Frontiers in Oncology. 2021; 11: 618612.

[15] Jing H, Xiuhong W, Ying Y, Zhenrong L, Xiyun C, Deping L, et al. Neoadjuvant chemotherapy combined with radical surgery for stage IB2/IIA2 cervical squamous cell carcinoma: a prospective, randomized controlled study of 35 patients. World Journal of Surgical Oncology. 2021; 19: 209.

[16] Li R, Lu S, Si J, Liu B, Wang H, Mei Y, et al. Prognostic value of responsiveness of neoadjuvant chemotherapy before surgery for patients with stage IB2/IIA2 cervical cancer. Gynecologic Oncology. 2013; 128: 524–529.

[17] Hu T, Li S, Chen Y, Shen J, Li X, Huang K, et al. Matched-case comparison of neoadjuvant chemotherapy in patients with FIGO stage IB1–IIB cervical cancer to establish selection criteria. European Journal of Cancer. 2012; 48: 2353–2360.

[18] 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: 1957–1963.

[19] Kim HS, Kim JY, Park NH, Kim K, Chung HH, Kim YB, et al. Matched-case comparison for the efficacy of neoadjuvant chemotherapy before surgery in FIGO stage IB1–IIA cervical cancer. Gynecologic Oncology. 2010; 119: 217–224.

[20] 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 (EJSO). 2013; 39: 115–124.

[21] National Comprehensive Cancer Network. Guidelines, Guidelines De-tail. 2022. Accessable at: https://www.nccn.org/guidelines/guidelines-detail/ (Accesssed: 15 November 2022).

[22] Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further 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.

[23] 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: 419–425.