J Gynecol Oncol.  2015 Jan;26(1):3-11. 10.3802/jgo.2015.26.1.3.

Clinical implication of surgically treated early-stage cervical cancer with multiple high-risk factors

Affiliations
  • 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Los Angeles County Medical Center, University of Southern California, Los Angeles, CA, USA. koji.matsuo@gmail.com
  • 2Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • 3Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 4Department of Gynecology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.

Abstract


OBJECTIVE
Presence of high-risk factor in cervical cancer is known to be associated with decreased survival outcomes. However, the significance of multiple high-risk factors in early-stage cervical cancer related to survival outcomes, recurrence patterns, and treatment implications is not well elucidated.
METHODS
A retrospective study was conducted for surgically treated cervical cancer patients (stage IA2-IIB, n=540). Surgical-pathological risk factors were examined and tumors expressing > or =1 high-risk factors (nodal metastasis, parametrial involvement, or positive surgical margin) were eligible for analysis (n=177, 32.8%). Survival analysis was performed based on the number of high-risk factors and the type of adjuvant therapy.
RESULTS
There were 68 cases (38.4%) expressed multiple high-risk factors (2 high-risk factors: n=58, 32.8%; 3 high-risk factors: n=10, 5.6%). Multiple high-risk factors remained an independent prognosticator for decreased survival outcomes after controlling for age, histology, stage, and treatment type (disease-free survival: hazard ratio [HR], 2.34; p=0.002; overall survival: HR, 2.32; p=0.007). Postoperatively, 101 cases (57.1%) received concurrent chemoradiotherapy (CCRT) and 76 cases (42.9%) received radiotherapy (RT) alone. CCRT was beneficial in single high-risk factor cases: HRs for CCRT over RT alone for cumulative risk of locoregional and distant recurrence, 0.27 (p=0.022) and 0.27 (p=0.005), respectively. However, tumor expressing multiple high-risk factors completely offset the benefit of CCRT over RT alone for the risk of distant recurrence: HR for locoregional and distant recurrence, 0.31 (p=0.071) and 0.99 (p=0.980), respectively.
CONCLUSION
Special consideration for the significance of multiple high-risk factors merits further investigation in the management of surgically treated early-stage cervical cancer.

Keyword

Combined Modality Therapy; Neoplasm Recurrence, Local; Retrospective Studies; Risk Factors; Survival Analysis; Uterine Cervical Neoplasms

MeSH Terms

Adult
Chemoradiotherapy, Adjuvant
Female
Humans
Hysterectomy/*methods
Lymphatic Metastasis
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Radiotherapy, Adjuvant
Retrospective Studies
Risk Factors
Survival Analysis
Uterine Cervical Neoplasms/pathology/*surgery

Figure

  • Fig. 1 Multiple high-risk factors and survival outcomes of early-stage cervical cancer. Numbers at risk are shown per group at the bottom of each figure. (A) Disease-free survival and (B) overall survival based on the number of high-risk factors (lymph node metastasis, parametrium invasion, and resection margin involvement). Cumulative risks for (C) locoregional and (D) distant recurrence are shown based on the number of high-risk factors.

  • Fig. 2 Multiple high-risk factors and recurrent pattern in early-stage cervical cancer. Numbers at risk are shown per group at the bottom of each figure. Cumulative risks for (A) locoregional and (B) distant recurrence are shown based on adjuvant therapy type in single high-risk factor cases. Cumulative risks for (C) locoregional and (D) distant recurrence are shown based on adjuvant therapy type in multiple high-risk factor cases. RT, radiotherapy; CCRT, concurrent chemoradiotherapy. *Log-rank test.


Reference

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61:69–90.
2. Waggoner SE. Cervical cancer. Lancet. 2003; 361:2217–2225.
3. Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1990; 38:352–357.
4. Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000; 18:1606–1613.
5. 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; 73:177–183.
6. Havrilesky LJ, Leath CA, Huh W, Calingaert B, Bentley RC, Soper JT, et al. Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer. Gynecol Oncol. 2004; 93:429–434.
7. Averette HE, Nguyen HN, Donato DM, Penalver MA, Sevin BU, Estape R, et al. Radical hysterectomy for invasive cervical cancer: a 25-year prospective experience with the Miami technique. Cancer. 1993; 71:4 Suppl. 1422–1437.
8. Lee YN, Wang KL, Lin MH, Liu CH, Wang KG, Lan CC, et al. Radical hysterectomy with pelvic lymph node dissection for treatment of cervical cancer: a clinical review of 954 cases. Gynecol Oncol. 1989; 32:135–142.
9. Monk BJ, Wang J, Im S, Stock RJ, Peters WA 3rd, Liu PY, et al. Rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial. Gynecol Oncol. 2005; 96:721–728.
10. Rotman M, Sedlis A, Piedmonte MR, Bundy B, Lentz SS, Muderspach LI, et al. A phase III randomized trial of postoperative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys. 2006; 65:169–176.
11. Matsuo K, Mabuchi S, Okazawa M, Matsumoto Y, Tsutsui T, Fujita M, et al. Utility of risk-weighted surgical-pathological factors in early-stage cervical cancer. Br J Cancer. 2013; 108:1348–1357.
12. Sartori E, Pasinetti B, Carrara L, Gambino A, Odicino F, Pecorelli S. Pattern of failure and value of follow-up procedures in endometrial and cervical cancer patients. Gynecol Oncol. 2007; 107:1 Suppl 1. S241–S247.
13. Eifel PJ, Winter K, Morris M, Levenback C, Grigsby PW, Cooper J, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol. 2004; 22:872–880.
14. Tavassoli FA, Devilee P. International Agency for Research on Cancer. World Health Organization. Tumors of the uterine cervix. In : Tavassoli FA, Devilee P, editors. International Agency for Research on Cancer. World Health Organization. Pathology and genetics of tumours of the breast and female genital organs. Lyon: IAPS Press;2003. p. 259–289.
15. Mabuchi S, Morishige K, Isohashi F, Yoshioka Y, Takeda T, Yamamoto T, et al. Postoperative concurrent nedaplatin-based chemoradiotherapy improves survival in early-stage cervical cancer patients with adverse risk factors. Gynecol Oncol. 2009; 115:482–487.
16. Mabuchi S, Okazawa M, Isohashi F, Matsuo K, Ohta Y, Suzuki O, et al. Radical hysterectomy with adjuvant radiotherapy versus definitive radiotherapy alone for FIGO stage IIB cervical cancer. Gynecol Oncol. 2011; 123:241–247.
17. Mabuchi S, Okazawa M, Isohashi F, Ohta Y, Maruoka S, Yoshioka Y, et al. Postoperative whole pelvic radiotherapy plus concurrent chemotherapy versus extended-field irradiation for early-stage cervical cancer patients with multiple pelvic lymph node metastases. Gynecol Oncol. 2011; 120:94–100.
18. Okazawa M, Mabuchi S, Isohashi F, Suzuki O, Ohta Y, Fujita M, et al. The prognostic significance of multiple pelvic node metastases in cervical cancer patients treated with radical hysterectomy plus adjuvant chemoradiotherapy. Int J Gynecol Cancer. 2012; 22:490–497.
19. Mabuchi S, Kimura T. Nedaplatin: a radiosensitizing agent for patients with cervical cancer. Chemother Res Pract. 2011; 2011:963159.
20. Fagundes H, Perez CA, Grigsby PW, Lockett MA. Distant metastases after irradiation alone in carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys. 1992; 24:197–204.
21. Vrdoljak E, Omrcen T, Novakovic ZS, Jelavic TB, Prskalo T, Hrepic D, et al. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy for women with locally advanced carcinoma of the uterine cervix: final results of a prospective phase II-study. Gynecol Oncol. 2006; 103:494–499.
22. Zhang MQ, Liu SP, Wang XE. Concurrent chemoradiotherapy with paclitaxel and nedaplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: preliminary results of a phase II study. Int J Radiat Oncol Biol Phys. 2010; 78:821–827.
23. Choi CH, Lee YY, Kim MK, Kim TJ, Lee JW, Nam HR, et al. A matched-case comparison to explore the role of consolidation chemotherapy after concurrent chemoradiation in cervical cancer. Int J Radiat Oncol Biol Phys. 2011; 81:1252–1257.
24. ClinicalTrials.gov. Chemotherapy and pelvic radiation therapy with or without additional chemotherapy in treating patients with high-risk early-stage cervical cancer after radical hysterectomy [Internet]. Bethesda, MD: US National Institutes of Health;2013. cited 2014 Jan 27. Available from: http://www.clinicaltrial.gov/ct2/show/NCT00980954?term=GOG+0724&rank=1.
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