Comparison of survival outcomes following radiotherapy versus radical hysterectomy in patients with stage IIA cervical squamous cell carcinoma

This study explored the differences in survival outcomes of cervical squamous cell carcinoma (SCC) patients diagnosed with stage IIA who underwent radical hysterectomy (RH) versus radiotherapy (RT). Eligible stage IIA cervical SCC cases were screened from the C4 database. They were divided into RH and RT groups based on their treatments and in a 1:2 ratio utilizing propensity score matching (PSM). Their 5-year overall survival (OS) and disease-free survival (DFS) before and after PSM were compared. Before PSM analysis, the results showed that patients from the RT group (n = 421) had significantly poorer 5-year OS and DFS rates compared with the RH group (n = 761) (OS: 77.2%vs. 85.6%, p < 0.001, HR = 1.789; DFS: 74.9% vs. 80.0%, p = 0.006, HR = 1.447). After stratification in a 1:2 ratio, PSM analysis results showed that the 5-year OS and DFS rates of stage IIA1 patients from the RT group (n = 226) were significantly poorer than the RH group (n = 429) (OS: 78.1% vs. 87.2%, p < 0.001, HR = 2.203; DFS: 78.2% vs. 83.7%, p = 0.011, HR = 1.681), while no significant difference in 5-year OS and DFS rates were observed between the RT (n = 173) and RH (n = 266) groups (OS: 75.2% vs. 83.8%, p = 0.054; DFS: 71.4% vs. 79.5%, p = 0.070) of stage IIA2 patients. RH was associated with better OS and DFS outcomes than RT in cervical SCC patients diagnosed with stage IIA disease. Subgroup analyses showed that RH had superior OS and DFS benefits than RT in stage IIA1 cases, while no significant difference in survival was observed for stage IIA2 patients.

Cervical cancer; Radical hysterectomy; Radiotherapy; Overall survival; Disease-free survival

[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: A Cancer Journal for Clinicians. 2018; 68: 394–424.

[2] Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. The Lancet. 1997; 350: 535–540.

[3] Kottmeier HL. Complications following radiation therapy in carcinoma of the cervix and their treatment. American Journal of Obstetrics and Gynecology. 1964; 88: 854–866.

[4] Piver MS, Marchetti DL, Patton T, Halpern J, Blumenson L, Driscoll DL. Radical hysterectomy and pelvic lymphadenectomy versus radiation therapy for small (less than or equal to 3 cm) stage IB cervical carcinoma. American Journal of Clinical Oncology. 1988; 11: 21–24.

[5] Morrow CP. Is pelvic radiation beneficial in the postoperative management of stage Ib squamous-cell carcinoma of the cervix with pelvic node metastasis treated by radical hysterectomy and pelvic lymphadenectomy?A report from the presidential panel at the 1979 annual meeting of the society of gynecologic oncologists. Gynecologic Oncology. 1980; 10: 105–110.

[6] Kinney WK, Alvarez RD, Reid GC, Schray MF, Soong S, Morley GW, et al. Value of adjuvant whole-pelvis irradiation after Wertheim hysterectomy for early-stage squamous carcinoma of the cervix with pelvic nodal metastasis: a matched-control study. Gynecologic Oncology. 1989; 34: 258–262.

[7] National Comprehensive Cancer Network. NCCN guidelines insights: Cervical Cancer, Version 1.2022. 2021. Available at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1426 (Accessed: 01 May 2022).

[8] Li P, Liu P, Yang Y, Wang L, Liu J, Bin X, et al. Hazard ratio analysis of laparoscopic radical hysterectomy for IA1 with LVSI-IIA2 cervical cancer: identifying the possible contraindications of laparoscopic surgery for cervical cancer. Frontiers in Oncology. 2020; 10: 1002.

[9] He J, Hao M, Liu P, Liu Z, Lang J, Bin X, et al. Comparison of laparoscopic and abdominal radical hysterectomy for early stage cervical cancer: oncologic outcomes based on tumor diameter. International Journal of Gynecologic Cancer. 2020; 30: 1308–1316.

[10] Liu P, Liang C, Lu A, Chen X, Liang W, Li D, et al. Risk factors and long-term impact of urologic complications during radical hysterectomy for cervical cancer in China, 2004–2016. Gynecologic Oncology. 2020; 158: 294–302.

[11] He F, Li W, Liu P, Kang S, Sun L, Zhao H, et al. Influence of uterine corpus invasion on prognosis in stage IA2-IIB cervical cancer: a multicenter retrospective cohort study. Gynecologic Oncology. 2020; 158: 273–281.

[12] Liu P, Lin L, Kong Y, Huo Z, Zhu L, Bin X, et al. Comparison of survival outcomes between radio-chemotherapy and radical hysterectomy with postoperative standard therapy in patients with stage IB1 to IIA2 cervical cancer: long-term oncological outcome analysis in 37 Chinese hospitals. BMC Cancer. 2020; 20: 189.

[13] Rosenbaum PR, Rubin DB. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. The American Statistician. 1985; 39: 33–38.

[14] 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: 1895–1904.

[15] Nitecki R, Ramirez PT, Frumovitz M, Krause KJ, Tergas AI, Wright JD, et al. Survival after minimally invasive vs open radical hysterectomy for early-stage cervical cancer: a systematic review and meta-analysis. JAMA Oncology. 2020; 6: 1019–1027.

[16] 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. The New England Journal of Medicine. 2018; 379: 1905–1914.

[17] Landoni F, Colombo A, Milani R, Placa F, Zanagnolo V, Mangioni C. Randomized study between radical surgery and radiotherapy for the treatment of stage IB-IIA cervical cancer: 20-year update. Journal of Gynecologic Oncology. 2017; 28: e34.

[18] Wu SG, Zhang WW, He ZY, Sun JY, Wang Y, Zhou J. Comparison of survival outcomes between radical hysterectomy and definitive radiochemotherapy in stage IB1 and IIA1 cervical cancer. Cancer Management and Research. 2017; 9: 813–819.

[19] Yamashita H, Nakagawa K, Tago M, Shiraishi K, Nakamura N, Ohtomo K, et al. Comparison between conventional surgery and radiotherapy for FIGO stage I–II cervical carcinoma: a retrospective Japanese study. Gynecologic Oncology. 2005; 97: 834–839.

[20] Bansal N, Herzog TJ, Shaw RE, Burke WM, Deutsch I, Wright JD. Primary therapy for early-stage cervical cancer: radical hysterectomy vs radiation. American Journal of Obstetrics and Gynecology. 2009; 201: 485. e1–485.e9.

[21] Brewster WR, Monk BJ, Ziogas A, Anton-Culver H, Yamada SD, Berman ML. Intent-to-treat analysis of stage Ib and IIa cervical cancer in the United States: radiotherapy or surgery 1988–1995. Obstetrics & Gynecology. 2001; 97: 248–254.

[22] Harding Y, Ooyama T, Nakamoto T, Wakayama A, Kudaka W, Inamine M, et al. Radiotherapy- or radical surgery-induced female sexual morbidity in stages IB and II Cervical Cancer. International Journal of Gynecologic Cancer. 2014; 24: 800–805.