Top

Published in:

Open Access 01-12-2021 | Cervical Cancer | Research

Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy

Authors: Se Ik Kim, Jeong Yun Kim, Chan Woo Wee, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Taek Sang Lee, Hye Won Jeon, Noh Hyun Park, Yong Sang Song, Tae Hun Kim

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH).

Methods

We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group).

Results

A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552–2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621–5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139).

Conclusions

Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.

Available only for authorised users

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;(3):209–49. https://doi.org/10.3322/caac.21660.

Lim MC, Won YJ, Ko MJ, Kim M, Shim SH, Suh DH, et al. Incidence of cervical, endometrial, and ovarian cancer in Korea during 1999-2015. J Gynecol Oncol. 2019;30(1):e38. https://doi.org/10.3802/jgo.2019.30.e38.CrossRefPubMed

Hong S, Won YJ, Park YR, Jung KW, Kong HJ, Lee ES. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2017. Cancer Res Treat. 2020;52(2):335–50. https://doi.org/10.4143/crt.2020.206.CrossRefPubMedPubMedCentral

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33. https://doi.org/10.3322/caac.21654.CrossRef

Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv72–83.CrossRef

Min KJ, Suh DH, Baba T, Chen X, Kim JW, Kobayashi Y, et al. Time for enhancing government-led primary prevention of cervical cancer. J Gynecol Oncol. 2021;32(1):e12. https://doi.org/10.3802/jgo.2021.32.e12.CrossRefPubMed

National Comprehensive Cancer Network. Cervical Cancer (Version 1.2021). Available at: http://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. .

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. Gynecol Oncol. 1999;73(2):177–83. https://doi.org/10.1006/gyno.1999.5387.CrossRefPubMed

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(20):1895–904. https://doi.org/10.1056/NEJMoa1806395.CrossRefPubMed

10.

FIGO Committee on Gynecologic Oncology. FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Int J Gynaecol Obstet. 2014;125(2):97–8. https://doi.org/10.1016/j.ijgo.2014.02.003.

11.

Querleu D, Cibula D, Abu-Rustum NR. 2017 update on the Querleu-morrow classification of radical hysterectomy. Ann Surg Oncol. 2017;24(11):3406–12. https://doi.org/10.1245/s10434-017-6031-z.CrossRefPubMedPubMedCentral

12.

Lim MC, Lee M, Shim SH, Nam EJ, Lee JY, Kim HJ, et al. Practice guidelines for management of cervical cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement. J Gynecol Oncol. 2017;28(3):e22. https://doi.org/10.3802/jgo.2017.28.e22.CrossRefPubMedPubMedCentral

13.

National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50. Accessed on: August 1, 2021.

14.

Kim SI, Cho JH, Seol A, Kim YI, Lee M, Kim HS, et al. Comparison of survival outcomes between minimally invasive surgery and conventional open surgery for radical hysterectomy as primary treatment in patients with stage IB1-IIA2 cervical cancer. Gynecol Oncol. 2019;153(1):3–12. https://doi.org/10.1016/j.ygyno.2019.01.008.CrossRefPubMed

15.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRef

16.

Lorvidhaya V, Chitapanarux I, Sangruchi S, Lertsanguansinchai P, Kongthanarat Y, Tangkaratt S, et al. Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial. Int J Radiat Oncol Biol Phys. 2003;55(5):1226–32. https://doi.org/10.1016/S0360-3016(02)04405-X.CrossRefPubMed

17.

Dueñas-González A, Zarbá JJ, Patel F, Alcedo JC, Beslija S, Casanova L, et al. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011;29(13):1678–85. https://doi.org/10.1200/JCO.2009.25.9663.CrossRefPubMed

18.

Tangjitgamol S, Tharavichitkul E, Tovanabutra C, Rongsriyam K, Asakij T, Paengchit K, et al. A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial. J Gynecol Oncol. 2019;30(4):e82. https://doi.org/10.3802/jgo.2019.30.e82.CrossRefPubMedPubMedCentral

19.

Mileshkin LR, Moore KN, Barnes E, Gebski V, Narayan K, Bradshaw N, et al. Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The randomized phase III OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274). 2021;39:LBA3-LBA.

20.

Sun LY, Wijeysundera DN, Tait GA, Beattie WS. Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery. Anesthesiology. 2015;123(3):515–23. https://doi.org/10.1097/ALN.0000000000000765.CrossRefPubMed

21.

Zhao H, Li L, Su H, Lin B, Zhang X, Xue S, et al. Concurrent paclitaxel/cisplatin chemoradiotherapy with or without consolidation chemotherapy in high-risk early-stage cervical cancer patients following radical hysterectomy: preliminary results of a phase III randomized study. Oncotarget. 2016;7(43):70969–78. https://doi.org/10.18632/oncotarget.10450.CrossRefPubMedPubMedCentral

22.

Huang H, Feng YL, Wan T, Zhang YN, Cao XP, Huang YW, et al. Effectiveness of sequential Chemoradiation vs concurrent Chemoradiation or radiation alone in adjuvant treatment after hysterectomy for cervical Cancer: the STARS phase 3 randomized clinical trial. JAMA Oncol. 2021;7(3):361–9. https://doi.org/10.1001/jamaoncol.2020.7168.CrossRefPubMed

23.

Kim H, Park W, Kim YS, Kim YJ. Chemoradiotherapy is not superior to radiotherapy alone after radical surgery for cervical cancer patients with intermediate-risk factor. J Gynecol Oncol. 2020;31(3):e35. https://doi.org/10.3802/jgo.2020.31.e35.CrossRefPubMed

24.

Foo J, Michor F. Evolution of acquired resistance to anti-cancer therapy. J Theor Biol. 2014;355:10–20. https://doi.org/10.1016/j.jtbi.2014.02.025.CrossRefPubMed

25.

Gupta S. Adjuvant chemotherapy in locally advanced cervical cancer: the ceiling remains unbroken. J Gynecol Oncol. 2019;30(4):e97. https://doi.org/10.3802/jgo.2019.30.e97.CrossRefPubMedPubMedCentral

26.

Organista-Nava J, Gómez-Gómez Y, Garibay-Cerdenares OL, Leyva-Vázquez MA, Illades-Aguiar B. Cervical cancer stem cell-associated genes: prognostic implications in cervical cancer. Oncol Lett. 2019;18(1):7–14. https://doi.org/10.3892/ol.2019.10307.CrossRefPubMedPubMedCentral

27.

Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11. https://doi.org/10.1038/35102167.CrossRefPubMed

28.

Cibula D, Dostalek L, Hillemanns P, Scambia G, Jarkovsky J, Persson J, et al. Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study. Eur J Cancer. 2021;143:88–100. https://doi.org/10.1016/j.ejca.2020.10.037.CrossRefPubMed

29.

Ferrandina G, Gallotta V, Federico A, Fanfani F, Ercoli A, Chiantera V, et al. Minimally invasive approaches in locally advanced cervical Cancer patients undergoing radical surgery after Chemoradiotherapy: a propensity score analysis. Ann Surg Oncol. 2021;28(7):3616–26. https://doi.org/10.1245/s10434-020-09302-y.CrossRefPubMed

30.

Moreno-Acosta P, Vallard A, Carrillo S, Gamboa O, Romero-Rojas A, Molano M, et al. Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma. Radiation oncology (London, England). 2017;12:120-.

31.

Uppal S, Gehrig PA, Peng K, Bixel KL, Matsuo K, Vetter MH, et al. Recurrence rates in patients with cervical Cancer treated with abdominal versus minimally invasive radical hysterectomy: a multi-institutional retrospective review study. J Clin Oncol. 2020;38(10):1030–40. https://doi.org/10.1200/JCO.19.03012.CrossRefPubMed

32.

Chiva L, Zanagnolo V, Querleu D, Martin-Calvo N, Arévalo-Serrano J, Căpîlna ME, et al. SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer. Int J Gynecol Cancer. 2020;30(9):1269–77. https://doi.org/10.1136/ijgc-2020-001506.CrossRefPubMed

33.

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 Oncol. 2020;6(7):1019–27. https://doi.org/10.1001/jamaoncol.2020.1694.CrossRefPubMed

Title: Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy
Authors: Se Ik Kim
Jeong Yun Kim
Chan Woo Wee
Maria Lee
Hee Seung Kim
Hyun Hoon Chung
Taek Sang Lee
Hye Won Jeon
Noh Hyun Park
Yong Sang Song
Tae Hun Kim
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Cervical Cancer
Cervical Cancer
Lymphadenectomy
Hysterectomy
Minimally Invasive Surgery
Cytostatic Therapy
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08940-z

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Image Credits

ASCO 2024 | Highlights of the Day: Breast cancer – metastatic/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Gynecologic Cancer/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Breast Cancer – local/regional/adjuvant/© 2024 American Society of Clinical Oncology, all rights reserved., Melanoma/© selvanegra / Getty Images / iStock, Antibody drug conjugated with cytotoxic payload/© Love Employee / Getty images / iStock

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Physician-patient communication of costs and financial burden of cancer and its treatment: a systematic review of clinical guidelines

Predicting disease progression in advanced non-small cell lung cancer with circulating neutrophil-derived and platelet-derived microparticles

Association of advanced age and cancer history with autoimmune disease in melanoma patients: a cross-sectional study

Evaluation of algorithms using administrative health and structured electronic medical record data to determine breast and colorectal cancer recurrence in a Canadian province

Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

Carboplatin versus cisplatin in combination with etoposide in the first-line treatment of small cell lung cancer: a pooled analysis