Early Cervical Cancer: Current Dilemmas of Staging and Surgery
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Purpose of Review
Advances in cervical cancer screening and treatment have resulted in high cure rates in developed countries for early-stage disease. Current research focuses on minimizing morbidity and maximizing quality of life.
Imaging has been disappointing in identifying small volume metastases. Sentinel lymph node biopsy represents a significant advantage with high sensitivity, low false negative rates, reduced morbidity, and equivalent survival in recent studies compared to pelvic lymphadenectomy. Non-radical surgical options are currently being investigated for early cervical cancer in a number of large prospective studies in patients at low risk for metastases.
Evidence suggests that sentinel lymph node biopsy and non-radical surgery are safe approaches for the staging and management of early cervical cancer in appropriately selected patients with the potential to significantly reduce treatment-related morbidity.
KeywordsEarly cervical cancer Uterine cervical neoplasm Cervical cancer staging Sentinel lymph nodes Pelvic lymphadenectomy Fertility-sparing surgery
Compliance with Ethical Standards
Conflict of Interest
Tiffany Zigras, Genevieve Lennox, Karla Willows, and Allan Covens declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from. http://globocan.iarc.fr. Accessed 2016/9/4.
- 3.Quinn MA, Benedet JL, Odicino F, Maisonneuve P, Beller U, Creasman WT, et al. Carcinoma of the cervix uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;(95 Suppl 1):S43–103. doi: 10.1016/S0020-7292(06)60030-1.
- 7.Amendola MA, Hricak H, Mitchell DG, Snyder B, Chi DS, Long HJ 3rd, et al. Utilization of diagnostic studies in the pretreatment evaluation of invasive cervical cancer in the United States: results of intergroup protocol ACRIN 6651/GOG 183. J Clin Oncol. 2005;23(30):7454–9. doi: 10.1200/JCO.2004.00.5397.CrossRefPubMedGoogle Scholar
- 9.Bhosale PR, Iyer RB, Ramalingam P, Schmeler KM, Wei W, Bassett RL, et al. Is MRI helpful in assessing the distance of the tumour from the internal os in patients with cervical cancer below FIGO stage IB2? Clin Radiol. 2016;71(6):515–22. doi: 10.1016/j.crad.2016.02.009.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Hricak H, Gatsonis C, Coakley FV, Snyder B, Reinhold C, Schwartz LH, et al. Early invasive cervical cancer: CT and MR imaging in preoperative evaluation—ACRIN/GOG comparative study of diagnostic performance and interobserver variability. Radiology. 2007;245(2):491–8. doi: 10.1148/radiol.2452061983.CrossRefPubMedGoogle Scholar
- 11.Mitchell DG, Snyder B, Coakley F, Reinhold C, Thomas G, Amendola M, et al. Early invasive cervical cancer: tumor delineation by magnetic resonance imaging, computed tomography, and clinical examination, verified by pathologic results, in the ACRIN 6651/GOG 183 Intergroup Study. J Clin Oncol. 2006;24(36):5687–94. doi: 10.1200/JCO.2006.07.4799.CrossRefPubMedGoogle Scholar
- 12.World Health Organization. Baseline country survey on medical devices 2010. Geneva: WHO Press; 2011.Google Scholar
- 13.Shen G, Zhou H, Jia Z, Deng H. Diagnostic performance of diffusion-weighted MRI for detection of pelvic metastatic lymph nodes in patients with cervical cancer: a systematic review and meta-analysis. Br J Radiol. 2015;88(1052):20150063. doi: 10.1259/bjr.20150063.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Hricak H, Gatsonis C, Chi DS, Amendola MA, Brandt K, Schwartz LH, et al. Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183. J Clin Oncol. 2005;23(36):9329–37. doi: 10.1200/JCO.2005.02.0354.CrossRefPubMedGoogle Scholar
- 17.Choi HJ, Roh JW, Seo SS, Lee S, Kim JY, Kim SK, et al. Comparison of the accuracy of magnetic resonance imaging and positron emission tomography/computed tomography in the presurgical detection of lymph node metastases in patients with uterine cervical carcinoma: a prospective study. Cancer. 2006;106(4):914–22. doi: 10.1002/cncr.21641.CrossRefPubMedGoogle Scholar
- 19.• Beiderwellen K, Grueneisen J, Ruhlmann V, Buderath P, Aktas B, Heusch P, et al. [(18)F]FDG PET/MRI vs. PET/CT for whole-body staging in patients with recurrent malignancies of the female pelvis: initial results. Eur J Nucl med Mol Imaging. 2015;42(1):56–65. doi: 10.1007/s00259-014-2902-8. PET/MRI has potential to add diagnostic confidence to metastatics pelvic lymph node assessment with reduced radiation to patients.CrossRefPubMedGoogle Scholar
- 23.Kodama J, Kusumoto T, Nakamura K, Seki N, Hongo A, Hiramatsu Y. Factors associated with parametrial involvement in stage IB1 cervical cancer and identification of patients suitable for less radical surgery. Gynecol Oncol. 2011;122(3):491–4. doi: 10.1016/j.ygyno.2011.05.038.CrossRefPubMedGoogle Scholar
- 25.Steed H, Rosen B, Murphy J, Laframboise S, De Petrillo D, Covens A. A comparison of laparoscopic-assisted radical vaginal hysterectomy and radical abdominal hysterectomy in the treatment of cervical cancer. Gynecol Oncol. 2004;93(3):588–93. doi: 10.1016/j.ygyno.2004.04.003.CrossRefPubMedGoogle Scholar
- 27.Hong JH, Choi JS, Lee JH, Son CE, Jeon SW, Bae JW, et al. Comparison of survival and adverse events between women with stage IB1 and stage IB2 cervical cancer treated by laparoscopic radical vaginal hysterectomy. Ann Surg Oncol. 2012;19(2):605–11. doi: 10.1245/s10434-011-1904-z.CrossRefPubMedGoogle Scholar
- 29.van de Lande J, von Mensdorff-Pouilly S, Lettinga RG, Piek JM, Verheijen RH. Open versus laparoscopic pelvic lymph node dissection in early stage cervical cancer: no difference in surgical or disease outcome. Int J Gynecol Cancer. 2012;22(1):107–14. doi: 10.1097/IGC.0b013e31822c273d.CrossRefPubMedGoogle Scholar
- 31.Naik R, Jackson KS, Lopes A, Cross P, Henry JA. Laparoscopic assisted radical vaginal hysterectomy versus radical abdominal hysterectomy—a randomised phase II trial: perioperative outcomes and surgicopathological measurements. BJOG. 2010;117(6):746–51. doi: 10.1111/j.1471-0528.2010.02479.x.CrossRefPubMedGoogle Scholar
- 32.• Campos LS, Limberger LF, Stein AT, Kalil AN. Postoperative pain and perioperative outcomes after laparoscopic radical hysterectomy and abdominal radical hysterectomy in patients with early cervical cancer: a randomised controlled trial. Trials. 2013;14:293. doi: 10.1186/1745-6215-14-293. Patients undergoing laparoscopic radical hysterectomy have less pain compared to those undergoing abdpoinal radical hysterectomy. Perioperative and post-operative outcomes were not significantly different.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.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(5):584–8. doi: 10.1016/j.jmig.2008.06.013.CrossRefPubMedGoogle Scholar
- 34.Obermair A, Frumovitz M, Ramirez PT. A phase III randomized clinical trial of laparoscopic or robotic radical hysterectomy versus abdominal radical hysterectomy in patients with early stage cervical cancer. Bethesda (MD): National Library of Medicine (US). 2016. URL of the record NLM Identifier: NCT00614211. https://clinicaltrials.gov/ct2/show/NCT00614211?term=laparoscopy+cervical+cancer&rank=4. Accessed 2016/12/12.
- 39.National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines): cervical cancer. Version I.2016. 2016. https://www.nccn.org/professionals/physician_gls/PDF/cervical.pdf.
- 41.• Kadkhodayan S, Hasanzadeh M, Treglia G, Azad A, Yousefi Z, Zarifmahmoudi L, et al. Sentinel node biopsy for lymph nodal staging of uterine cervix cancer: a systematic review and meta-analysis of the pertinent literature. Eur J Surg Oncol. 2015;41(1):1–20. doi: 10.1016/j.ejso.2014.09.010. Sentinel lymph node mapping showed a pooled detection rate of 89.2% and a pooled sensitivity of 90%. In addition, sentinel lymph nodes were able to be identified outside of the usual pelvic lymphadenectomy borders.CrossRefPubMedGoogle Scholar
- 42.Magrina JF. Primary surgery for stage IB-IIA cervical cancer, including short-term and long-term morbidity and treatment in pregnancy. J Natl Cancer Inst Monogr. 1996;21:53–9.Google Scholar
- 44.Niikura H, Okamoto S, Otsuki T, Yoshinaga K, Utsunomiya H, Nagase S, et al. Prospective study of sentinel lymph node biopsy without further pelvic lymphadenectomy in patients with sentinel lymph node-negative cervical cancer. Int J Gynecol Cancer. 2012;22(7):1244–50. doi: 10.1097/IGC.0b013e318263f06a.CrossRefPubMedGoogle Scholar
- 45.Lecuru F, Mathevet P, Querleu D, Leblanc E, Morice P, Darai E, 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(13):1686–91. doi: 10.1200/JCO.2010.32.0432.CrossRefPubMedGoogle Scholar
- 46.• Mathevet P, Lecuru F, editors. Effect of sentinel lymph-node biopsy alone on the morbidity of the surgical treatment of early cervical cancer: results from the prospective randomized study Senticol2. ASCO Annual Meeting Proceedings. 2015. In patients with negative sentinel lymph nodes, those who underwent sentinel lymph node biopsy alone had less surgical morbidity compared to those who underwent complete pelvic lymphadenectomy. There were no false negative sentinel lymph nodes in the study.Google Scholar
- 47.• Ruscito I, Gasparri ML, Braicu EI, Bellati F, Raio L, Sehouli J, et al. Sentinel node mapping in cervical and endometrial cancer: indocyanine green versus other conventional dyes—a meta-analysis. Ann Surg Oncol. 2016;23(11):3749–56. doi: 10.1245/s10434-016-5236-x. Detection rates of sentinel lymph nodes by indocyanine green (ICG) are equivalent to that of combination blue dye and radiactive tracer. ICG is likely to be favored given its ease of use and safety.CrossRefPubMedGoogle Scholar
- 48.• Lennox GK, Covens A. Can sentinel lymph node biopsy replace pelvic lymphadenectomy for early cervical cancer? Gynecol Oncol. 2017;144(1):16–20. doi: 10.1016/j.ygyno.2016.08.337. Patients with negative nodes by sentinel lymph node biopsy alone or complete pelvic lymphadenectomy had no difference in two or five recurrence-free survival. Those who had complete pelvic lymphadenectomy had increased operative time, transfusions, and post-operative infections compared to those who had sentinel lymph node biopsy alone.CrossRefPubMedGoogle Scholar
- 49.Gortzak-Uzan L, Jimenez W, Nofech-Mozes S, Ismiil N, Khalifa MA, Dube V, et al. Sentinel lymph node biopsy vs. pelvic lymphadenectomy in early stage cervical cancer: is it time to change the gold standard? Gynecol Oncol. 2010;116(1):28–32. doi: 10.1016/j.ygyno.2009.10.049.CrossRefPubMedGoogle Scholar
- 51.Bergmark K, Avall-Lundqvist E, Dickman PW, Henningsohn L, Steineck G. Lymphedema and bladder-emptying difficulties after radical hysterectomy for early cervical cancer and among population controls. Int J Gynecol Cancer. 2006;16(3):1130–9. doi: 10.1111/j.1525-1438.2006.00601.x.CrossRefPubMedGoogle Scholar
- 55.Benedetti-Panici P, Maneschi F, D'Andrea G, Cutillo G, Rabitti C, Congiu M, et al. Early cervical carcinoma: the natural history of lymph node involvement redefined on the basis of thorough parametrectomy and giant section study. Cancer. 2000;88(10):2267–74. doi: 10.1002/(SICI)1097-0142(20000515)88:10<2267::AID-CNCR10>3.0.CO;2-9.CrossRefPubMedGoogle Scholar
- 63.• Aerts L, Enzlin P, Verhaeghe J, Poppe W, Vergote I, Amant F. Long-term sexual functioning in women after surgical treatment of cervical cancer stages IA to IB: a prospective controlled study. Int J Gynecol Cancer. 2014;24(8):1527–34. doi: 10.1097/IGC.0000000000000236. Women with cervical cancer who underwent surgical management had signficiantly worse sexual dysfunction, psychological function, and quality of partner relationship compared to healthy controls.CrossRefPubMedGoogle Scholar
- 66.Stegeman M, Louwen M, van der Velden J, ten Kate FJ, den Bakker MA, Burger CW, et al. The incidence of parametrial tumor involvement in select patients with early cervix cancer is too low to justify parametrectomy. Gynecol Oncol. 2007;105(2):475–80. doi: 10.1016/j.ygyno.2007.01.016.CrossRefPubMedGoogle Scholar
- 69.Klat J, Sevcik L, Simetka O, Graf P, Dvorackova J, Kraft O. What is the risk for parametrial involvement in women with early-stage cervical cancer with tumour <20 mm and with negative sentinel lymph nodes? Aust N Z J Obstet Gynaecol. 2012;52(6):540–4. doi: 10.1111/ajo.12015.CrossRefPubMedGoogle Scholar
- 70.Gemer O, Eitan R, Gdalevich M, Mamanov A, Piura B, Rabinovich A, et al. Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement. Eur J Surg Oncol. 2013;39(1):76–80. doi: 10.1016/j.ejso.2012.10.013.CrossRefPubMedGoogle Scholar
- 72.Lee JY, Youm J, Kim JW, Cho JY, Kim MA, Kim TH, et al. Identifying a low-risk group for parametrial involvement in microscopic stage IB1 cervical cancer using criteria from ongoing studies and a new MRI criterion. BMC Cancer. 2015;15(167):167. doi: 10.1186/s12885-015-1184-2.CrossRefPubMedPubMedCentralGoogle Scholar
- 77.• Bouchard-Fortier G, Reade CJ, Covens A. Non-radical surgery for small early-stage cervical cancer. Is it time? Gynecol Oncol. 2014;132(3):624–7. doi: 10.1016/j.ygyno.2014.01.037. Of women with early cervical cancer who met low-risk criteria and underwent non-radical surgical treatment (simple hysterectomy or cone biopsy), they had excellent oncological outcomes with no recurrences after a median follow-up time of 21 months.CrossRefPubMedGoogle Scholar
- 83.Abu-Rustum NR, Neubauer N, Sonoda Y, Park KJ, Gemignani M, Alektiar KM, et al. Surgical and pathologic outcomes of fertility-sparing radical abdominal trachelectomy for FIGO stage IB1 cervical cancer. Gynecol Oncol. 2008;111(2):261–4. doi: 10.1016/j.ygyno.2008.07.002.CrossRefPubMedPubMedCentralGoogle Scholar
- 84.• 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(6):e240–53. doi: 10.1016/S1470-2045(16)30032-8. Fertility-sparing surgery can be considered for women with stage IB1 cervical cancer. The approach must take into account tumor size and presence of lymphovascular space invasion. Onologic and obstetric outcomes are accepable, but must be weighed against risks.CrossRefPubMedGoogle Scholar
- 86.Zivanovic O, Leitao MM Jr, Park KJ, Zhao H, Diaz JP, Konner J, et al. Small cell neuroendocrine carcinoma of the cervix: analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy. Gynecol Oncol. 2009;112(3):590–3. doi: 10.1016/j.ygyno.2008.11.010.CrossRefPubMedGoogle Scholar
- 87.• Speiser D, Kohler C, Schneider A, Mangler M. Radical vaginal trachelectomy: a fertility-preserving procedure in early cervical cancer in young women. Dtsch Arztebl Int. 2013;110(17):289–95. doi: 10.3238/arztebl.2013.0289. In women with early cervical cancer with tumor size <2 cm who wish to preserve fertility, radical vaginal trachelectomy is feasible and oncologically safe. Patients, who do go on to get pregnant, have higher rates of preterm births.PubMedPubMedCentralGoogle Scholar