Invasive cervical cancer: Staging and evaluation of lymph nodes
- Michael Frumovitz, MD, MPH
Michael Frumovitz, MD, MPH
- Associate Professor of Gynecologic Oncology
- MD Anderson Cancer Center
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Deborah Levine, MD
Deborah Levine, MD
- Section Editor — Imaging
- Professor of Radiology
- Director of Ob/Gyn Ultrasound
- Department of Radiology
- Beth Israel Deaconess Medical Center
Cancer of the uterine cervix is staged using a clinical, rather than a surgical staging system, which is the approach used for other gynecologic tumors [1,2]. Surgical staging is potentially more accurate . However, the International Federation of Gynecology and Obstetrics (FIGO) has determined that clinical staging is preferable for several reasons: it is more accessible for low resource settings, in which cervical cancer remains the most common malignancy among women; it may be better for assessing locally advanced disease (ie, tumor size, vaginal and parametrial involvement); and it avoids surgery in women who are not candidates for surgical treatment .
Tumor stage is determined at the time of primary diagnosis of cervical cancer and is not altered, even upon recurrence. This convention also applies to other gynecologic cancers. Accurate pretreatment staging of cervical cancer is critical, as it determines therapy (ie, surgery, chemoradiation, chemotherapy alone) and prognosis (table 1).
The staging and evaluation of lymph nodes for cervical cancer will be reviewed here. Cervical cancer screening and prevention, epidemiology, risk factors, clinical manifestations, diagnosis, and treatment are discussed separately. (See "Screening for cervical cancer" and "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis" and "Management of early-stage cervical cancer" and "Management of locally advanced cervical cancer" and "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)
The diagnosis of cervical cancer is made based upon histologic evaluation of a cervical biopsy. After histologic confirmation, the extent of disease is determined. Two parallel staging systems are available, both of which use clinical rather than surgical criteria to assign disease stage (see 'Staging procedure' below). The corresponding stages of the two systems are shown in the table (table 2).
FIGO system — The International Federation of Gynecology and Obstetrics (FIGO) collaborated with the International Union Against Cancer (IUCC) to formulate the most recent version of the FIGO system for cervical cancer [1-3]. The FIGO staging system is largely based upon physical examination and a limited number of endoscopic diagnostic procedures and imaging studies (see 'Staging procedure' below). The FIGO system is used more commonly than the Tumor, Nodes, Metastasis (TNM) system.
- Benedet JL, Bender H, Jones H 3rd, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000; 70:209.
- Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009; 105:103.
- Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet 2009; 105:107.
- Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69.
- Cervix Uteri. In: American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.395.
- Lagasse LD, Creasman WT, Shingleton HM, et al. Results and complications of operative staging in cervical cancer: experience of the Gynecologic Oncology Group. Gynecol Oncol 1980; 9:90.
- LaPolla JP, Schlaerth JB, Gaddis O, Morrow CP. The influence of surgical staging on the evaluation and treatment of patients with cervical carcinoma. Gynecol Oncol 1986; 24:194.
- Hricak H, Gatsonis C, Chi DS, 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; 23:9329.
- Quinn MA, Benedet JL, Odicino F, 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.
- Amendola MA, Hricak H, Mitchell DG, 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; 23:7454.
- Grigsby PW, Siegel BA, Dehdashti F. Lymph node staging by positron emission tomography in patients with carcinoma of the cervix. J Clin Oncol 2001; 19:3745.
- Scheidler J, Hricak H, Yu KK, et al. Radiological evaluation of lymph node metastases in patients with cervical cancer. A meta-analysis. JAMA 1997; 278:1096.
- Greer BE, Koh WJ, Abu-Rustum NR, et al. Cervical cancer. J Natl Compr Canc Netw 2010; 8:1388.
- Mitchell DG, Snyder B, Coakley F, 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; 24:5687.
- Bhosale P, Peungjesada S, Devine C, et al. Role of magnetic resonance imaging as an adjunct to clinical staging in cervical carcinoma. J Comput Assist Tomogr 2010; 34:855.
- Ozsarlak O, Tjalma W, Schepens E, et al. The correlation of preoperative CT, MR imaging, and clinical staging (FIGO) with histopathology findings in primary cervical carcinoma. Eur Radiol 2003; 13:2338.
- Hancke K, Heilmann V, Straka P, et al. Pretreatment staging of cervical cancer: is imaging better than palpation?: Role of CT and MRI in preoperative staging of cervical cancer: single institution results for 255 patients. Ann Surg Oncol 2008; 15:2856.
- Balleyguier C, Sala E, Da Cunha T, et al. Staging of uterine cervical cancer with MRI: guidelines of the European Society of Urogenital Radiology. Eur Radiol 2011; 21:1102.
- Bipat S, Glas AS, van der Velden J, et al. Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review. Gynecol Oncol 2003; 91:59.
- Showalter TN, Miller TR, Huettner P, et al. 18F-fluorodeoxyglucose-positron emission tomography and pathologic tumor size in early-stage invasive cervical cancer. Int J Gynecol Cancer 2009; 19:1412.
- Singh N, Arif S. Histopathologic parameters of prognosis in cervical cancer--a review. Int J Gynecol Cancer 2004; 14:741.
- Follen M, Levenback CF, Iyer RB, et al. Imaging in cervical cancer. Cancer 2003; 98:2028.
- Kumar R, Chauhan A, Jana S, Dadparvar S. Positron emission tomography in gynecological malignancies. Expert Rev Anticancer Ther 2006; 6:1033.
- Rajendran JG, Greer BE. Expanding role of positron emission tomography in cancer of the uterine cervix. J Natl Compr Canc Netw 2006; 4:463.
- Wolfson AH. Magnetic resonance imaging and positron-emission tomography imaging in the 21st century as tools for the evaluation and management of patients with invasive cervical carcinoma. Semin Radiat Oncol 2006; 16:186.
- Sironi S, Buda A, Picchio M, et al. Lymph node metastasis in patients with clinical early-stage cervical cancer: detection with integrated FDG PET/CT. Radiology 2006; 238:272.
- Selman TJ, Mann C, Zamora J, et al. Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and meta-analysis. CMAJ 2008; 178:855.
- Choi HJ, Roh JW, Seo SS, 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; 106:914.
- Loft A, Berthelsen AK, Roed H, et al. The diagnostic value of PET/CT scanning in patients with cervical cancer: a prospective study. Gynecol Oncol 2007; 106:29.
- Boughanim M, Leboulleux S, Rey A, et al. Histologic results of para-aortic lymphadenectomy in patients treated for stage IB2/II cervical cancer with negative [18F]fluorodeoxyglucose positron emission tomography scans in the para-aortic area. J Clin Oncol 2008; 26:2558.
- Havrilesky LJ, Kulasingam SL, Matchar DB, Myers ER. FDG-PET for management of cervical and ovarian cancer. Gynecol Oncol 2005; 97:183.
- Ramirez PT, Jhingran A, Macapinlac HA, et al. Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer: a prospective correlation of surgical findings with positron emission tomography/computed tomography findings. Cancer 2011; 117:1928.
- Leblanc E, Gauthier H, Querleu D, et al. Accuracy of 18-fluoro-2-deoxy-D-glucose positron emission tomography in the pretherapeutic detection of occult para-aortic node involvement in patients with a locally advanced cervical carcinoma. Ann Surg Oncol 2011; 18:2302.
- Uzan C, Souadka A, Gouy S, et al. Analysis of morbidity and clinical implications of laparoscopic para-aortic lymphadenectomy in a continuous series of 98 patients with advanced-stage cervical cancer and negative PET-CT imaging in the para-aortic area. Oncologist 2011; 16:1021.
- Cosin JA, Fowler JM, Chen MD, et al. Pretreatment surgical staging of patients with cervical carcinoma: the case for lymph node debulking. Cancer 1998; 82:2241.
- Goff BA, Muntz HG, Paley PJ, et al. Impact of surgical staging in women with locally advanced cervical cancer. Gynecol Oncol 1999; 74:436.
- 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.
- Robison K, Holman LL, Moore RG. Update on sentinel lymph node evaluation in gynecologic malignancies. Curr Opin Obstet Gynecol 2011; 23:8.
- Gold MA, Tian C, Whitney CW, et al. Surgical versus radiographic determination of para-aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma: a Gynecologic Oncology Group Study. Cancer 2008; 112:1954.
- Sevin BU, Nadji M, Averette HE, et al. Microinvasive carcinoma of the cervix. Cancer 1992; 70:2121.
- Reynolds EA, Tierney K, Keeney GL, et al. Analysis of outcomes of microinvasive adenocarcinoma of the uterine cervix by treatment type. Obstet Gynecol 2010; 116:1150.
- Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas, number 35, May 2002. Obstet Gynecol 2002; 99:855.
- Benedet JL, Anderson GH. Stage IA carcinoma of the cervix revisited. Obstet Gynecol 1996; 87:1052.
- Todo Y, Yamamoto R, Minobe S, et al. Risk factors for postoperative lower-extremity lymphedema in endometrial cancer survivors who had treatment including lymphadenectomy. Gynecol Oncol 2010; 119:60.
- Dowdy SC, Aletti G, Cliby WA, et al. Extra-peritoneal laparoscopic para-aortic lymphadenectomy--a prospective cohort study of 293 patients with endometrial cancer. Gynecol Oncol 2008; 111:418.
- Zanvettor PH, Filho DF, Neves AR, et al. Laparoscopic surgical staging of locally advanced cervix cancer (IB2 to IVA): initial experience. Gynecol Oncol 2011; 120:358.
- Moore KN, Gold MA, McMeekin DS, et al. Extraperitoneal para-aortic lymph node evaluation for cervical cancer via pfannenstiel incision: technique and peri-operative outcomes. Gynecol Oncol 2008; 108:466.
- Sonoda Y, Leblanc E, Querleu D, et al. Prospective evaluation of surgical staging of advanced cervical cancer via a laparoscopic extraperitoneal approach. Gynecol Oncol 2003; 91:326.
- Marnitz S, Köhler C, Roth C, et al. Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer? Gynecol Oncol 2005; 99:536.
- 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.
- Hauspy J, Beiner M, Harley I, et al. Sentinel lymph nodes in early stage cervical cancer. Gynecol Oncol 2007; 105:285.
- Rob L, Robova H, Halaska MJ, et al. Current status of sentinel lymph node mapping in the management of cervical cancer. Expert Rev Anticancer Ther 2013; 13:861.
- Frumovitz M, Ramirez PT, Levenback CF. Lymphatic mapping and sentinel lymph node detection in women with cervical cancer. Gynecol Oncol 2008; 110:S17.
- Esajas MD, Duk JM, de Bruijn HW, et al. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer. J Clin Oncol 2001; 19:3960.
- Chan YM, Ng TY, Ngan HY, Wong LC. Monitoring of serum squamous cell carcinoma antigen levels in invasive cervical cancer: is it cost-effective? Gynecol Oncol 2002; 84:7.
- Gaarenstroom KN, Kenter GG, Bonfrer JM, et al. Can initial serum cyfra 21-1, SCC antigen, and TPA levels in squamous cell cervical cancer predict lymph node metastases or prognosis? Gynecol Oncol 2000; 77:164.
- Massuger LF, Koper NP, Thomas CM, et al. Improvement of clinical staging in cervical cancer with serum squamous cell carcinoma antigen and CA 125 determinations. Gynecol Oncol 1997; 64:473.
- Lin H, ChangChien CC, Huang EY, et al. The role of pretreatment squamous cell carcinoma antigen in predicting nodal metastasis in early stage cervical cancer. Acta Obstet Gynecol Scand 2000; 79:140.
- Duk JM, Groenier KH, de Bruijn HW, et al. Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma. J Clin Oncol 1996; 14:111.
- Bolli JA, Doering DL, Bosscher JR, et al. Squamous cell carcinoma antigen: clinical utility in squamous cell carcinoma of the uterine cervix. Gynecol Oncol 1994; 55:169.
- Duk JM, de Bruijn HW, Groenier KH, et al. Cancer of the uterine cervix: sensitivity and specificity of serum squamous cell carcinoma antigen determinations. Gynecol Oncol 1990; 39:186.
- Gocze PM, Vahrson HW, Freeman DA. Serum levels of squamous cell carcinoma antigen and ovarian carcinoma antigen (CA 125) in patients with benign and malignant diseases of the uterine cervix. Oncology 1994; 51:430.
- Tomás C, Risteli J, Risteli L, et al. Use of various epithelial tumor markers and a stromal marker in the assessment of cervical carcinoma. Obstet Gynecol 1991; 77:566.
- Sproston AR, Roberts SA, Davidson SE, et al. Serum tumour markers in carcinoma of the uterine cervix and outcome following radiotherapy. Br J Cancer 1995; 72:1536.
- Bolger BS, Dabbas M, Lopes A, Monaghan JM. Prognostic value of preoperative squamous cell carcinoma antigen level in patients surgically treated for cervical carcinoma. Gynecol Oncol 1997; 65:309.
- Callet N, Cohen-Solal Le Nir CC, Berthelot E, Pichon MF. Cancer of the uterine cervix: sensitivity and specificity of serum Cyfra 21.1 determinations. Eur J Gynaecol Oncol 1998; 19:50.
- Gaarenstroom KN, Bonfrer JM, Kenter GG, et al. Clinical value of pretreatment serum Cyfra 21-1, tissue polypeptide antigen, and squamous cell carcinoma antigen levels in patients with cervical cancer. Cancer 1995; 76:807.
- Scambia G, Benedetti Panici P, Foti E, et al. Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer. J Clin Oncol 1994; 12:2309.
- Juang CM, Wang PH, Yen MS, et al. Application of tumor markers CEA, TPA, and SCC-Ag in patients with low-risk FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix. Gynecol Oncol 2000; 76:103.
- Reesink-Peters N, van der Velden J, Ten Hoor KA, et al. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer. J Clin Oncol 2005; 23:1455.
- STAGING SYSTEMS
- FIGO system
- TNM system
- STAGING PROCEDURE
- FURTHER EVALUATION
- Imaging studies
- - Clinical approach
- - Tumor size and local spread
- - Lymph node metastases
- - Upper urinary tract involvement
- Surgical evaluation of lymph nodes
- - Lymph node dissection
- - Sentinel lymph node biopsy
- Laboratory evaluation
- - Routine evaluation
- - Tumor markers
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS