NCCN: Continuing Education
Accreditation Statement
This activity is designated to meet the educational needs of physicians, nurses, and pharmacists involved in the management of patients with cancer. There is no fee for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.
NCCN designates this educational activity for a maximum of 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.
National Comprehensive Cancer Network is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. NCCN designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of continuing education credit in states that recognize ACPE accredited providers. This is a knowledge-based activity. UAN: 0836-0000-15-004-H01-P
All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 66% minimum passing score and complete the evaluation at http://education.nccn.org/node/64364; and 4) view/print certificate.
Release date: April 17, 2015; Expiration date: April 17, 2016
Learning Objectives
Upon completion of this activity, participants will be able to:
-
Integrate into professional practice the updates to the NCCN Guidelines for Cervical Cancer
-
Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Cervical Cancer
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Overview
The NCCN Cervical Cancer Panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecologic oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cervical Cancer include evidence-based recommendations for the assessment and management of cervical cancer. The panel updates the NCCN Guidelines on an annual basis, with additional interim updates as appropriate. Notable recent updates include modifications to the recommended systemic therapy regimens for recurrent or metastatic cervical cancer, and new information and guidance related to surgical staging and evaluation. The latest full version of these guidelines is available online at NCCN.org.
Background
Carcinoma of the uterine cervix, commonly known as cervical cancer, remains a significant public health
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
Despite these advancements, cervical cancer is the fourth most common cancer among women worldwide.6 In 2012, an estimated 528,000 new cases of cervical cancer were diagnosed and 266,000 women died from the disease.6 Importantly, cervical cancer has a dramatically uneven impact across the globe; more than 85% of all cervical cancers and cervical cancer-related deaths occur in developing countries.6–9 Although cervical cancer rates are generally decreasing among women in developed countries because of the availability of effective prevention and screening methods, incidence in the United States remains high among Hispanic/Latino, black, and Asian women.10–14 An estimated 12,900 new cases of cervical cancer are expected in the United States in 2015, and 4100 people will die of the disease.15 Cervical cancer can often be successfully treated when detected early. The current 5-year survival rates for women with early-stage, locally advanced, and metastatic cervical cancers are 91%, 57%, and 16%, respectively.16
Newly-Approved Combination Regimens for Advanced Disease
Recent research has focused on systemic regimens that are able to improve survival for patients with persistent, recurrent, or metastatic cervical cancer.
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
A recent randomized phase III trial from the Gynecologic Oncology Group (GOG 240) examined 2 primary questions: (1) whether topotecan/paclitaxel was superior to the standard cisplatin/paclitaxel regimen for treating persistent, recurrent, or metastatic cervical cancer; and (2) whether the addition of bevacizumab to cisplatin/paclitaxel or topotecan/paclitaxel could improve survival. Accordingly, this trial included patients with advanced cervical cancer (n=452) who received 1 of 4 possible combination regimens: cisplatin/paclitaxel; topotecan/paclitaxel; cisplatin/paclitaxel/bevacizumab; or topotecan/paclitaxel/bevacizumab. Analysis of pooled data from the 2 bevacizumab-containing regimens revealed significant improvements in overall survival among patients receiving the antiangiogenic agent (17.0 vs 13.3 months; P=.004).23 Compared with cisplatin/paclitaxel, topotecan/paclitaxel was not shown to be superior.23 Although bevacizumab led to higher toxicity (eg, hypertension, thromboembolic events,
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Guidelines Insights: Cervical Cancer, Version 2.2015
Version 2.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 4; 10.6004/jnccn.2015.0055
NCCN Recommendations
During the 2015 NCCN Cervical Cancer Guidelines update, the panel made several revisions to the systemic therapy recommendations for advanced disease based on new clinical trial data (see CERV-D 1 of 2, above). After discussing the clinical data and recent drug approvals, the panel voted to modify the category assigned to several existing recommendations (see NCCN Categories of Evidence and Consensus on page 397 for category descriptions).
Based on GOG 240 data recently published by Tewari et al,23 the list of recommended first-line combination therapies was modified(see CERV-D 1 of 2, above). First, the panel voted to recategorize cisplatin/paclitaxel/bevacizumab from category 2A to category 1 based on the availability of positive survival data from a phase III randomized trial. For patients who cannot receive or access bevacizumab, the panel also voted to recommend cisplatin/paclitaxel, a preexisting standard of care regimen, as an alternative category 1 option. Combination regimens using a nonplatinum chemotherapy backbone (eg, topotecan/paclitaxel/bevacizumab and topotecan/paclitaxel) were also added to the list of recommended combination regimens. During the panel’s initial 2014 guideline update, topotecan/paclitaxel/bevacizumab was included as a category 2B regimen and topotecan/paclitaxel was added as a category 2A recommendation. Upon the FDA’s August 2014 approval of bevacizumab in combination with cisplatin/paclitaxel or topotecan/paclitaxel for treating cervical cancer, the panel voted to include topotecan/paclitaxel/bevacizumab as a category 1 recommendation.
Several other regimens were recategorized after panel discussions. After considering the strength of the data supporting cisplatin/gemcitabine relative to that for alternative combination regimens, this recommendation was changed to category 3 (see CERV-D 1 of 2, opposite page). The panel also revisited the recommended single-agent second-line therapies (see CERV-D 1 of 2, opposite page). Although most of the second-line therapy options were recognized as category 2B recommendations, the panel noted the categorization of pemetrexed and vinorelbine, which were category 3 at that time. After reevaluating data for each of the second-line single-therapy options, the panel came to consensus that each option had data of relatively equivalent strength and quality. Therefore, the panel decided to change pemetrexed and vinorelbine to category 2B recommendations.
Surgical Approaches for Evaluating and Treating Cervical Cancer
Bolstered by the publication of new clinical data, advances in imaging, radiotherapy, and surgical techniques have expanded the range of treatment options available for staging and treating early-stage cervical cancer. New data suggest that fertility-sparing treatment options can be considered in select patients without negatively impacting oncologic outcomes (reviewed by Ramirez et al28). Additionally, recent data suggest that conservative approaches to lymph node assessment/dissection may reduce morbidity without harming survival. However, because of the complex nature of treatment decisions and the need to consider individual disease risk factors, considerable debate still surrounds the decision to forego more aggressive therapy for conservative approaches. Because high levels of expertise and experience are required to safely and effectively execute fertility-sparing/conservative treatment approaches, a new section describing recommended principles of evaluation and surgical staging was incorporated into the NCCN Guidelines during the annual 2014 update. This Insights article discusses relevant data and panel recommendations for various surgical approaches.
Sentinel Lymph Node Mapping
Recent data suggest that sentinel lymph node (SLN) biopsy may be useful for decreasing the need for pelvic lymphadenectomy in patients with early-stage cervical cancer.29,30 Prospective studies generally support the feasibility of SLN detection in patients with early-stage cervical cancer and suggest that pelvic lymph node dissection can be safely avoided in a significant proportion of early-stage cases.29–40 In a meta-analysis of data from 1112 patients with cervical cancer who underwent SLN biopsy, pooled data generated a detection rate of 92.2%, pooled sensitivity was 88.8%, and negative predictive values were 95%.41 Subgroup analyses were performed according to route of surgery (laparoscopy vs laparotomy), detection method (dye only, isotope only, or combination of both tracers), and pathologic assessment method (hematoxylin-eosin only vs hematoxylineosin with immunohistochemistry). Higher SLN detection rates were observed for laparoscopy, dual-tracer approaches, and pathologic assessment using immunohistochemistry.
However, study data also highlight the limited sensitivity of this approach and potential to miss SLN micrometastases and isolated tumor cells using intraoperative assessment (ie, frozen section or imprint cytology).32,36,38 The sensitivity of this approach seems to be better in patients with tumors 2 cm or less in diameter.29,31,33,42 Ultrastaging of detected SLNs has been shown to provide enhanced detection of micrometastases.34,35
The SENTICOL longitudinal study demonstrated the utility of SLN mapping to uncover unusual lymph drainage patterns.33 Additionally, this study revealed that bilateral SLN detection and biopsy provided a more reliable assessment of sentinel nodal metastases and led to fewer false-negatives than unilateral SLN biopsy.30 Generally, research supports ipsilateral lymphadenectomy if no SLNs are detected on a given side of the pelvis.30,43
NCCN Recommendations: Lymph Node Assessment: Panel members were divided over whether the SLN technique has been sufficiently validated for routine use.31,32,36,37 Based on existing data, the panel recommends consideration of SLN mapping (category 2B) for early-stage disease and emphasizes that best detection and mapping results are in tumors with a diameter of less than 2 cm. The panel strongly emphasizes that adherence to the SLN mapping algorithm is important; surgeons should perform side-specific nodal dissection in any cases of failed mapping and remove all suspicious or grossly enlarged nodes regardless of SLN mapping.29 To provide additional detail and guidance on this procedure, the panel added new SLN treatment principles to the guidelines during the 2014 update (see CERV-A 3 and 4 of 7, pages 398 and 399).
Fertility-Sparing Treatment for Early-Stage Cervical Cancer
Microinvasive disease (International Federation of Gynecology and Obstetrics [FIGO] stage IA1 with no lymphovascular space invasion [LVSI]) is associated with an extremely low incidence of lymphatic metastasis,44–47 and conservative treatment with conization seems to be safe in individuals with no evidence of LVSI.48
For stage IA2 and IB1 cervical cancers with lesions that are 2 cm or less in diameter, radical trachelectomy provides a fertility-sparing option that may be appropriate for select patients. In a radical trachelectomy, the cervix, vaginal margins, and supporting ligaments are removed while leaving the main body and fundus of the uterus intact.49 Laparoscopic pelvic lymphadenectomy accompanies the procedure and can be performed with or without SLN mapping.50 Research suggests that radical trachelectomy is oncologically safe for patients with stage IA2 or IB1 cervical cancer with lesions that are 2 cm or less in diameter.51–56 However, select studies have begun to investigate the safety of this procedure for patients with stage IA2 or IB1 cervical cancer with lesions that are more than 2 cm in diameter.57–59
Both vaginal and abdominal approaches to the radical trachelectomy procedure have been examined. Abdominal radical trachelectomy provides a broader resection of the parametria than a vaginal approach, but provides a less conservative alternative for fertility preservation.55,60 Multiple case series have evaluated safety and outcomes with vaginal versus abdominal approaches to radical trachelectomy,54,61–63 including systematic reviews on vaginal50 and abdominal64 radical trachelectomy.
NCCN Recommendations: The panel agrees that fertility-sparing approaches may be considered in highly selected patients who have been thoroughly counseled regarding disease risk and prenatal and perinatal issues (see CERV-A 1 of 7, page 397). In stage IA1 individuals with evidence of LVSI, a reasonable conservative approach is conization (with negative margins) in addition to pelvic lymphadenectomy (category 2A) with the option for SLN mapping (category 2B for SLN). Based on existing data, the panel suggests that radical trachelectomy with lymph node dissection (category 2A) offers a reasonable fertility-sparing treatment option for select patients with stage IA2 or IB1 cervical cancer with lesions that are 2 cm or less in diameter.28,55,65 Vaginal radical trachelectomy (category 2A) is recommended for carefully selected patients with lesions with a diameter of 2 cm or less.56,60,61 Laparoscopic pelvic lymphadenectomy should accompany the procedure and can be performed with or without SLN mapping (category 2B for SLN).
Conclusions
Important recent updates to the NCCN Guidelines for Cervical Cancer are highlighted in this report. The NCCN Guidelines are updated at least annually and more often when new high-quality clinical data become available in the interim. The most up-to-date version of these continuously evolving guidelines is available at NCCN.org. The recommendations in the NCCN Guidelines are based on evidence from clinical trials, when available, combined with expert consensus of the NCCN Cervical Cancer Panel. Independent medical judgment is required to apply these guidelines individually to provide optimal care. The physician and patient have the responsibility to jointly explore and select the most appropriate option from among the available alternatives. When possible, consistent with NCCN philosophy, the NCCN panel strongly encourages participation in prospective clinical trials.
References
- 1.↑
Kjaer SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst 2010;102:1478–1488.
- 2.↑
Rodriguez AC, Schiffman M, Herrero R et al.. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst 2010;102:315–324.
- 3.↑
Arbyn M, Dillner J. Review of current knowledge on HPV vaccination: an appendix to the European Guidelines for Quality Assurance in Cervical Cancer Screening. J Clin Virol 2007;38:189–197.
- 4.
Rambout L, Hopkins L, Hutton B, Fergusson D. Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials. CMAJ 2007;177:469–479.
- 5.↑
Chan JK, Berek JS. Impact of the human papilloma vaccine on cervical cancer. J Clin Oncol 2007;25:2975–2982.
- 6.↑
Cervical Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012. International Agency for Research on Cancer and World Health Organization; 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed January 26, 2015.
- 7.
Jemal A, Bray F, Center MM et al.. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.
- 8.
Arbyn M, Castellsague X, de Sanjose S et al.. Worldwide burden of cervical cancer in 2008. Ann Oncol 2011;22:2675–2686.
- 9.↑
Singh GK, Azuine RE, Siahpush M. Global inequalities in cervical cancer incidence and mortality are linked to deprivation, low socioeconomic status, and human development. Int J MCH and AIDS 2012;1:17–30.
- 10.↑
Barnholtz-Sloan J, Patel N, Rollison D et al.. Incidence trends of invasive cervical cancer in the United States by combined race and ethnicity. Cancer Causes Control 2009;20:1129–1138.
- 11.
Wang SS, Carreon JD, Gomez SL, Devesa SS. Cervical cancer incidence among 6 asian ethnic groups in the United States, 1996 through 2004. Cancer 2010;116:949–956.
- 12.
Howe HL, Wu X, Ries LAG et al.. Annual report to the nation on the status of cancer, 1975-2003, featuring cancer among U.S. Hispanic/Latino populations. Cancer 2006;107:1711–1742.
- 13.
Sherman ME, Wang SS, Carreon J, Devesa SS. Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival. Cancer 2005;103:1258–1264.
- 14.↑
Singh GK. Rural-urban trends and patterns in cervical cancer mortality, incidence, stage, and survival in the United States, 1950-2008. J Community Health 2012;37:217–223.
- 16.↑
SEER Program Stat Fact Sheets: Cancer of the Cervix Uteri. SEER Web site. Available at: http://seer.cancer.gov/statfacts/html/cervix.html. Accessed January 30, 2015.
- 17.↑
Thigpen T, Shingleton H, Homesley H et al.. Cis-platinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Cancer 1981;48:899–903.
- 18.↑
Moore DH, Blessing JA, McQuellon RP et al.. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 2004;22:3113–3119.
- 19.↑
Long HJ 3rd, Bundy BN, Grendys EC Jr et al.. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 2005;23:4626–4633.
- 20.
Moore DH. Chemotherapy for advanced, recurrent, and metastatic cervical cancer. J Natl Compr Canc Netw 2008;6:53–57.
- 21.
Tao X, Hu W, Ramirez PT, Kavanagh JJ. Chemotherapy for recurrent and metastatic cervical cancer. Gynecol Oncol 2008;110:67–71.
- 22.
Monk BJ, Sill MW, McMeekin DS et al.. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2009;27:4649–4655.
- 23.↑
Tewari KS, Sill MW, Long HJ III et al.. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014;370:734–743.
- 24.↑
Kitagawa R, Katsumata N, Ando M et al.. A multi-institutional phase II trial of paclitaxel and carboplatin in the treatment of advanced or recurrent cervical cancer. Gynecol Oncol 2012;125:307–311.
- 25.↑
Kitagawa R, Katsumata N, Shibata T et al.. A randomized, phase III trial of paclitaxel plus carboplatin (TC) versus paclitaxel plus cisplatin (TP) in stage IVb, persistent or recurrent cervical cancer: Japan Clinical Oncology Group study (JCOG0505) [abstract]. J Clin Oncol 2012;30(Suppl 15):Abstract 5006.
- 26.↑
Penson RT, Huang H, Tewari KS et al.. Patient reported outcomes in a practice changing randomized trial of bevacizumab in the treatment of advanced cervical cancer: a gynecologic oncology group study [abstract]. Presented at the European Cancer Congress 2013; September 27-October 1, 2013; Amsterdam, Netherlands.
- 27.↑
National Cancer Institute. FDA approval for bevacizumab. 2014. Available at: http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab. Accessed August 29, 2014.
- 28.↑
Ramirez PT, Pareja R, Rendon GJ et al.. Management of low-risk early-stage cervical cancer: should conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care? Gynecol Oncol 2014;132:254–259.
- 29.↑
Cormier B, Diaz JP, Shih K et al.. Establishing a sentinel lymph node mapping algorithm for the treatment of early cervical cancer. Gynecol Oncol 2011;122:275–280.
- 30.↑
Lecuru F, Mathevet P, Querleu D et al.. Bilateral negative sentinel nodes accurately predict absence of lymph node metastasis in early cervical cancer: results of the SENTICOL study. J Clin Oncol 2011;29:1686–1691.
- 31.↑
Altgassen C, Hertel H, Brandstadt A et al.. Multicenter validation study of the sentinel lymph node concept in cervical cancer: AGO Study Group. J Clin Oncol 2008;26:2943–2951.
- 32.↑
Bats AS, Buenerd A, Querleu D et al.. Diagnostic value of intraoperative examination of sentinel lymph node in early cervical cancer: a prospective, multicenter study. Gynecol Oncol 2011;123:230–235.
- 33.↑
Bats AS, Mathevet P, Buenerd A et al.. The sentinel node technique detects unexpected drainage pathways and allows nodal ultrastaging in early cervical cancer: insights from the multicenter prospective SENTICOL study. Ann Surg Oncol 2013;20:413–422.
- 34.↑
Cibula D, Abu-Rustum NR, Dusek L et al.. Bilateral ultrastaging of sentinel lymph node in cervical cancer: lowering the false-negative rate and improving the detection of micrometastasis. Gynecol Oncol 2012;127:462–466.
- 35.↑
Cibula D, Abu-Rustum NR, Dusek L et al.. Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer. Gynecol Oncol 2012;124:496–501.
- 36.↑
Fader AN, Edwards RP, Cost M et al.. Sentinel lymph node biopsy in early-stage cervical cancer: utility of intraoperative versus postoperative assessment. Gynecol Oncol 2008;111:13–17.
- 37.↑
Lecuru F, Bats A, Mathevet P et al.. Impact of sentinel lymph node biopsy on staging of early cervical cancer: results of a prospective, multicenter study [abstract]. J Clin Oncol 2009;27(Suppl 18):Abstract CRA5506.
- 38.↑
Slama J, Dundr P, Dusek L, Cibula D. High false negative rate of frozen section examination of sentinel lymph nodes in patients with cervical cancer. Gynecol Oncol 2013;129:384–388.
- 39.
van de Lande J, Torrenga B, Raijmakers PGHM et al.. Sentinel lymph node detection in early stage uterine cervix carcinoma: a systematic review. Gynecol Oncol 2007;106:604–613.
- 40.↑
Andikyan V, Khoury-Collado F, Denesopolis J et al.. Cervical conization and sentinel lymph node mapping in the treatment of stage I cervical cancer: is less enough? Int J Gynecol Cancer 2014;24:113–117.
- 41.↑
Wu Y, Li Z, Wu H, Yu J. Sentinel lymph node biopsy in cervical cancer: a meta-analysis. Mol Clin Oncol 2013;1:1025–1030.
- 42.↑
Eiriksson LR, Covens A. Sentinel lymph node mapping in cervical cancer: the future? BJOG 2012;119:129–133.
- 43.↑
Darlin L, Persson J, Bossmar T et al.. The sentinel node concept in early cervical cancer performs well in tumors smaller than 2 cm. Gynecol Oncol 2010;117:266–269.
- 44.↑
Ueki M, Okamoto Y, Misaki O et al.. Conservative therapy for microinvasive carcinoma of the uterine cervix. Gynecol Oncol 1994;53:109–113.
- 45.
Al-Kalbani M, McVeigh G, Nagar H, McCluggage WG. Do FIGO stage IA and small (</=2 cm) IB1 cervical adenocarcinomas have a good prognosis and warrant less radical surgery? Int J Gynecol Cancer 2012;22:291–295.
- 46.
Webb JC, Key CR, Qualls CR, Smith HO. Population-based study of microinvasive adenocarcinoma of the uterine cervix. Obstet Gynecol 2001;97:701–706.
- 47.↑
Sevin BU, Nadji M, Averette HE et al.. Microinvasive carcinoma of the cervix. Cancer 1992;70:2121–2128.
- 48.↑
Wright JD, NathavithArana R, Lewin SN et al.. Fertility-conserving surgery for young women with stage IA1 cervical cancer: safety and access. Obstet Gynecol 2010;115:585–590.
- 49.↑
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.
- 50.↑
Beiner ME, Covens A. Surgery insight: radical vaginal trachelectomy as a method of fertility preservation for cervical cancer. Nat Clin Pract Oncol 2007;4:353–361.
- 51.↑
Park JY, Joo WD, Chang SJ et al.. Long-term outcomes after fertility-sparing laparoscopic radical trachelectomy in young women with early-stage cervical cancer: an Asan Gynecologic Cancer Group (AGCG) study. J Surg Oncol 2014;110:252–257.
- 52.
Gizzo S, Ancona E, Saccardi C et al.. Radical trachelectomy: the first step of fertility preservation in young women with cervical cancer (review). Oncol Rep 2013;30:2545–2554.
- 53.
Raju SK, Papadopoulos AJ, Montalto SA et al.. Fertility-sparing surgery for early cervical cancer-approach to less radical surgery. Int J Gynecol Cancer 2012;22:311–317.
- 54.↑
Abu-Rustum NR, Sonoda Y. Fertility-sparing surgery in early-stage cervical cancer: indications and applications. J Natl Compr Canc Netw 2010;8:1435–1438.
- 55.↑
Diaz JP, Sonoda Y, Leitao MM et al.. Oncologic outcome of fertility-sparing radical trachelectomy versus radical hysterectomy for stage IB1 cervical carcinoma. Gynecol Oncol 2008;111:255–260.
- 56.↑
Plante M, Gregoire J, Renaud MC, Roy M. The vaginal radical trachelectomy: an update of a series of 125 cases and 106 pregnancies. Gynecol Oncol 2011;121:290–297.
- 57.↑
Lanowska M, Mangler M, Speiser D et al.. Radical vaginal trachelectomy after laparoscopic staging and neoadjuvant chemotherapy in women with early-stage cervical cancer over 2 cm: oncologic, fertility, and neonatal outcome in a series of 20 patients. Int J Gynecol Cancer 2014;24:586–593.
- 58.
Wethington SL, Sonoda Y, Park KJ et al.. Expanding the indications for radical trachelectomy: a report on 29 patients with stage IB1 tumors measuring 2 to 4 centimeters. Int J Gynecol Cancer 2013;23:1092–1098.
- 59.↑
Lintner B, Saso S, Tarnai L et al.. Use of abdominal radical trachelectomy to treat cervical cancer greater than 2 cm in diameter. Int J Gynecol Cancer 2013;23:1065–1070.
- 60.↑
Abu-Rustum NR, Sonoda Y, Black D et al.. Fertility-sparing radical abdominal trachelectomy for cervical carcinoma: technique and review of the literature. Gynecol Oncol 2006;103:807–813.
- 61.↑
Cao DY, Yang JX, Wu XH 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.
- 62.
Einstein MH, Park KJ, Sonoda Y et al.. Radical vaginal versus abdominal trachelectomy for stage IB1 cervical cancer: a comparison of surgical and pathologic outcomes. Gynecol Oncol 2009;112:73–77.
- 63.↑
Wethington SL, Cibula D, Duska LR et al.. An international series on abdominal radical trachelectomy: 101 patients and 28 pregnancies. Int J Gynecol Cancer 2012;22:1251–1257.
- 64.↑
Pareja R, Rendon GJ, Sanz-Lomana CM et al.. Surgical, oncological, and obstetrical outcomes after abdominal radical trachelectomy - a systematic literature review. Gynecol Oncol 2013;131:77–82.
- 65.↑
Abu-Rustum NR, Tal MN, DeLair D et al.. Radical abdominal trachelectomy for stage IB1 cervical cancer at 15-week gestation. Gynecol Oncol 2010;116:151–152.
