Minimally invasive versus open radical trachelectomy for early-stage cervical cancer: protocol for a multicenter randomized controlled trial in China

Xiaopei Chao, Lei Li, Ming Wu, Huanwen Wu, Shuiqing Ma, Xianjie Tan, Sen Zhong, Jinghe Lang, Xiaopei Chao, Lei Li, Ming Wu, Huanwen Wu, Shuiqing Ma, Xianjie Tan, Sen Zhong, Jinghe Lang

Abstract

Background: There are limited data comparing the oncologic and fertility outcomes of patients with early-stage cervical cancer (CC) treated by minimally invasive radical trachelectomy (MIRT) or abdominal radical trachelectomy (ART). The purpose of this multicenter study is to compare the oncologic and fertility outcomes of patients treated by MIRT or ART in a randomized controlled manner in China.

Methods: This is a noninferiority, randomized controlled trial performed at 28 Chinese centers; the study is designed to compare the oncologic and fertility outcomes of patients treated by MIRT (robot-assisted or laparoscopic RT) or ART. Patients will be recruited if they have been diagnosed with stage IA1 (with lymphovascular space invasion), IA2, or IB1 CC (with a maximum tumor diameter ≤ 2 cm) in the FIGO 2009 staging system and histological subtypes of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma and if they are also aged 18 to 40 years. These candidates will be randomly assigned to undergo MIRT or ART. The primary endpoint will be disease-free survival. Secondary endpoints will consist of overall and disease-free survival rates, fertility outcomes, and quality of life. A total of 414 patients are needed to accomplish the study goal, with 90.1% power at a 0.050 significance level to detect an equivalence hazard ratio of 0.75 in the ART group, considering 20% loss to follow-up.

Discussion: The results of the trial should provide robust evidence to surgeons regarding options for the surgical approach in patients with early-stage CC who have a strong willingness to preserve fertility.

Trial registration: ClinicalTrials.gov NCT03739944 . Registered on November 14, 2018.

Keywords: Cervical cancer; Clinical pregnant rate; Live birth rate; Overall survival; Progression-free survival; Quality of life; Radical trachelectomy; Randomised controlled trial.

Conflict of interest statement

All authors declare that they have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram of the study. ARH, abdominal radical hysterectomy; MIRT, minimally invasive radical trachelectomy; ART, abdominal radical trachelectomy
Fig. 2
Fig. 2
SPIRIT figure of the study

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
    1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–132. doi: 10.3322/caac.21338.
    1. Capilna ME, Szabo B, Becsi J, Ioanid N, Moldovan B. Radical trachelectomy performed during pregnancy: a review of the literature. Int J Gynecol Cancer. 2016;26:758–762. doi: 10.1097/IGC.0000000000000655.
    1. Smith JR, Boyle DC, Corless DJ, Ungar L, Lawson AD, Del Priore G, et al. Abdominal radical trachelectomy: a new surgical technique for the conservative management of cervical carcinoma. Br J Obstet Gynaecol. 1997;104:1196–1200. doi: 10.1111/j.1471-0528.1997.tb10946.x.
    1. Dargent D, Martin X, Sacchetoni A, Mathevet P. Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients. Cancer. 2000;88:1877–1882. doi: 10.1002/(SICI)1097-0142(20000415)88:8<1877::AID-CNCR17>;2-W.
    1. Obermair A, Gebski V, Frumovitz M, Soliman PT, Schmeler KM, Levenback C, et al. A phase III randomized clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients with early stage cervical cancer. J Minim Invasive Gynecol. 2008;15:584–588. doi: 10.1016/j.jmig.2008.06.013.
    1. Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med. 2018;379:1895–1904. doi: 10.1056/NEJMoa1806395.
    1. Melamed A, Margul DJ, Chen L, Keating NL, Del Carmen MG, Yang J, et al. Survival after minimally invasive radical hysterectomy for early-stage cervical cancer. N Engl J Med. 2018;379:1905–1914. doi: 10.1056/NEJMoa1804923.
    1. Cao DY, Yang JX, Wu XH, Chen YL, Li L, Liu KJ, et al. Comparisons of vaginal and abdominal radical trachelectomy for early-stage cervical cancer: preliminary results of a multi-center research in China. Br J Cancer. 2013;109:2778–2782. doi: 10.1038/bjc.2013.656.
    1. Bentivegna E, Gouy S, Maulard A, Chargari C, Leary A, Morice P. Oncological outcomes after fertility-sparing surgery for cervical cancer: a systematic review. Lancet Oncol. 2016;17:e240–ee53. doi: 10.1016/S1470-2045(16)30032-8.
    1. Li X, Li J, Wu X. Incidence, risk factors and treatment of cervical stenosis after radical trachelectomy: a systematic review. Eur J Cancer. 2015;51:1751–1759. doi: 10.1016/j.ejca.2015.05.012.
    1. Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, et al. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986;4:14–22. doi: 10.1200/JCO.1986.4.1.14.
    1. Greimel ER, Kuljanic Vlasic K, Waldenstrom AC, Duric VM, Jensen PT, Singer S, et al. The European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire cervical cancer module: EORTC QLQ-CX24. Cancer. 2006;107:1812–1822. doi: 10.1002/cncr.22217.
    1. Hua CH, Guo HM, Guan XL, Kong FJ, Hou RJ, Zhang XY, et al. Validation of the European Organization for Research and Treatment of Cancer cervical cancer module for Chinese patients with cervical cancer. Patient Prefer Adherence. 2013;7:1061–1066. doi: 10.2147/PPA.S52498.
    1. ter Kuile MM, Brauer M, Laan E. The Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS): psychometric properties within a Dutch population. J Sex Marital Ther. 2006;32:289–304. doi: 10.1080/00926230600666261.
    1. Swift S, Woodman P, O’Boyle A, Kahn M, Valley M, Bland D, et al. Pelvic Organ Support Study (POSST): the distribution, clinical definition, and epidemiologic condition of pelvic organ support defects. Am J Obstet Gynecol. 2005;192:795–806. doi: 10.1016/j.ajog.2004.10.602.
    1. Costales A, Michener C, Escobar-Rodriguez PF. Radical trachelectomy for early stage cervical cancer. Curr Treat Options in Oncol. 2018;19:75. doi: 10.1007/s11864-018-0591-4.
    1. Common Terminology Criteria for Adverse Events (CTCAE) v4.03 (). National Cancer Institute.
    1. Pareja R, Rendon GJ, Sanz-Lomana CM, Monzon O, Ramirez PT. Surgical, oncological, and obstetrical outcomes after abdominal radical trachelectomy - a systematic literature review. Gynecol Oncol. 2013;131:77–82. doi: 10.1016/j.ygyno.2013.06.010.
    1. Li X, Li J, Wen H, Ju X, Chen X, Xia L, et al. The survival rate and surgical morbidity of abdominal radical trachelectomy versus abdominal radical hysterectomy for stage IB1 cervical cancer. Ann Surg Oncol. 2016;23:2953–2958. doi: 10.1245/s10434-016-5216-1.
    1. Lakatos E. Sample sizes based on the log-rank statistic in complex clinical trials. Biometrics. 1988;44:229–241. doi: 10.2307/2531910.
    1. Salvo G, Ramirez PT, Leitao M, Cibula D, Fotopoulou C, Kucukmetin A, et al. International radical trachelectomy assessment: IRTA study. Int J Gynecol Cancer. 2019;29:635–638. doi: 10.1136/ijgc-2019-000273.
    1. Mabuchi S, Kimura T. Extraperitoneal radical trachelectomy with pelvic lymphadenectomy: a novel fertility-preserving option for early stage cervical cancer patients. Int J Gynecol Cancer. 2017;27:537–542. doi: 10.1097/IGC.0000000000000918.
    1. Schreuder HW, Verheijen RH. Robotic surgery. BJOG. 2009;116:198–213. doi: 10.1111/j.1471-0528.2008.02038.x.
    1. Seamon LG, Fowler JM, Richardson DL, Carlson MJ, Valmadre S, Phillips GS, et al. A detailed analysis of the learning curve: robotic hysterectomy and pelvic-aortic lymphadenectomy for endometrial cancer. Gynecol Oncol. 2009;114:162–167. doi: 10.1016/j.ygyno.2009.04.017.
    1. Wethington SL, Cibula D, Duska LR, Garrett L, Kim CH, Chi DS, et al. An international series on abdominal radical trachelectomy: 101 patients and 28 pregnancies. Int J Gynecol Cancer. 2012;22:1251–1257. doi: 10.1097/IGC.0b013e318263eee2.
    1. Ungar L, Palfalvi L, Hogg R, Siklos P, Boyle DC, Del Priore G, et al. Abdominal radical trachelectomy: a fertility-preserving option for women with early cervical cancer. BJOG. 2005;112:366–369. doi: 10.1111/j.1471-0528.2004.00421.x.
    1. Capilna ME, Ioanid N, Scripcariu V, Gavrilescu MM, Szabo B. Abdominal radical trachelectomy: a romanian series. Int J Gynecol Cancer. 2014;24:615–619. doi: 10.1097/IGC.0000000000000076.
    1. Evans JM, Karram MM, Mahdy A, Robertshaw D. Urinary tract injury at the time of laparoscopic and robotic surgery: presentation and management. Female Pelvic Med Reconstr Surg. 2013;19:249–252. doi: 10.1097/SPV.0b013e318294600a.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する