Management of recurrent or metastatic cervical cancer
- Jason D Wright, MD
Jason D Wright, MD
- Sol Goldman Associate Professor of Obstetrics and Gynecology
- Chief, Division of Gynecologic Oncology
- Columbia University College of Physicians and Surgeons
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Department Chair, Gynecologic Oncology
- University of Washington Medical Center
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Head of Women's Cancers, Lifespan Cancer Institute
- Director of Medical Oncology, Rhode Island Hospital
- Associate Professor of Medicine, Warren Alpert Medical School of Brown University
Although uncommon at initial diagnosis, metastatic disease will develop in 15 to 61 percent women with cervical cancer, usually within the first two years of completing treatment [1,2]. In the majority of cases, metastatic cervical cancer is not curable. However, for some patients who present with recurrent disease in the pelvis (locoregional recurrence) or with limited distant metastatic disease, surgical treatment is potentially curative.
Histologically, squamous cell carcinoma (SCC), adenocarcinoma, and adenosquamous carcinomas account for approximately 70, 25, and 3 to 5 percent of all cervical cancers, respectively (table 1) . Rarer histologies include neuroendocrine or small cell carcinomas.
The management of recurrent or metastatic cervical cancer will be discussed here. Specific issues regarding patterns of relapse after treatment are discussed separately. (See "Invasive cervical cancer: Patterns of recurrence and posttreatment surveillance".)
Recurrent cervical cancer can present as a local recurrence or as metastatic disease.
Locally recurrent cervical cancer usually presents with vaginal symptoms (ie, discharge, bleeding, dyspareunia, or pain). On pelvic exam, a mass or nodularity at the vaginal cuff, which may extend to the pelvic side wall, may be visualized or palpated. Disease within the vagina (or vaginal vault) can be tender to palpation and/or prone to bleeding easily.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Ries LAG, Harkins D, Krapcho M, et al. SEER Cancer Statistics Review, 1975 to 2003. National Cancer Institute, Bethesda, MD 2006.
- SEER data for 2000-2004 http://seer.cancer.gov/ (Accessed on April 25, 2011).
- Hong JH, Tsai CS, Lai CH, et al. Recurrent squamous cell carcinoma of cervix after definitive radiotherapy. Int J Radiat Oncol Biol Phys 2004; 60:249.
- Fulcher AS, O'Sullivan SG, Segreti EM, Kavanagh BD. Recurrent cervical carcinoma: typical and atypical manifestations. Radiographics 1999; 19 Spec No:S103.
- Patel CN, Nazir SA, Khan Z, et al. 18F-FDG PET/CT of cervical carcinoma. AJR Am J Roentgenol 2011; 196:1225.
- Chung HH, Jo H, Kang WJ, et al. Clinical impact of integrated PET/CT on the management of suspected cervical cancer recurrence. Gynecol Oncol 2007; 104:529.
- Pallardy A, Bodet-Milin C, Oudoux A, et al. Clinical and survival impact of FDG PET in patients with suspicion of recurrent cervical carcinoma. Eur J Nucl Med Mol Imaging 2010; 37:1270.
- van der Veldt AA, Buist MR, van Baal MW, et al. Clarifying the diagnosis of clinically suspected recurrence of cervical cancer: impact of 18F-FDG PET. J Nucl Med 2008; 49:1936.
- Lim MC, Lee HS, Seo SS, et al. Pathologic diagnosis and resection of suspicious thoracic metastases in patients with cervical cancer through thoracotomy or video-assisted thoracic surgery. Gynecol Oncol 2010; 116:478.
- Friedlander M, Grogan M, U.S. Preventative Services Task Force. Guidelines for the treatment of recurrent and metastatic cervical cancer. Oncologist 2002; 7:342.
- Rutledge S, Carey MS, Prichard H, et al. Conservative surgery for recurrent or persistent carcinoma of the cervix following irradiation: is exenteration always necessary? Gynecol Oncol 1994; 52:353.
- Maneo A, Landoni F, Cormio G, et al. Radical hysterectomy for recurrent or persistent cervical cancer following radiation therapy. Int J Gynecol Cancer 1999; 9:295.
- Barney BM, Petersen IA, Dowdy SC, et al. Intraoperative Electron Beam Radiotherapy (IOERT) in the management of locally advanced or recurrent cervical cancer. Radiat Oncol 2013; 8:80.
- Martínez-Monge R, Jurado M, Aristu JJ, et al. Intraoperative electron beam radiotherapy during radical surgery for locally advanced and recurrent cervical cancer. Gynecol Oncol 2001; 82:538.
- Haasbeek CJ, Uitterhoeve AL, van der Velden J, et al. Long-term results of salvage radiotherapy for the treatment of recurrent cervical carcinoma after prior surgery. Radiother Oncol 2008; 89:197.
- Moore DH, Tian C, Monk BJ, et al. Prognostic factors for response to cisplatin-based chemotherapy in advanced cervical carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol 2010; 116:44.
- Long HJ 3rd. Management of metastatic cervical cancer: review of the literature. J Clin Oncol 2007; 25:2966.
- Movva S, Rodriguez L, Arias-Pulido H, Verschraegen C. Novel chemotherapy approaches for cervical cancer. Cancer 2009; 115:3166.
- Gadducci A, Tana R, Cosio S, Cionini L. Treatment options in recurrent cervical cancer (Review). Oncol Lett 2010; 1:3.
- Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014; 370:734.
- Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet 2017; 390:1654.
- Penson RT, Huang HQ, Wenzel LB, et al. Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240). Lancet Oncol 2015; 16:301.
- 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.
- Kitagawa R, Katsumata N, Shibata T, et al. Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505. J Clin Oncol 2015; 33:2129.
- Lorusso D, Petrelli F, Coinu A, et al. A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer. Gynecol Oncol 2014; 133:117.
- Scatchard K, Forrest JL, Flubacher M, et al. Chemotherapy for metastatic and recurrent cervical cancer. Cochrane Database Syst Rev 2012; 10:CD006469.
- Weiss GR, Green S, Hannigan EV, et al. A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Gynecol Oncol 1990; 39:332.
- Alberts DS, Blessing JA, Landrum LM, et al. Phase II trial of nab-paclitaxel in the treatment of recurrent or persistent advanced cervix cancer: A gynecologic oncology group study. Gynecol Oncol 2012; 127:451.
- Morris M, Brader KR, Levenback C, et al. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol 1998; 16:1094.
- Lacava JA, Leone BA, Machiavelli M, et al. Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma. J Clin Oncol 1997; 15:604.
- Muggia FM, Blessing JA, Method M, et al. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 2004; 92:639.
- McGuire WP, Blessing JA, Moore D, et al. Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol 1996; 14:792.
- Curtin JP, Blessing JA, Webster KD, et al. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 2001; 19:1275.
- Kudelka AP, Winn R, Edwards CL, et al. An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Anticancer Drugs 1997; 8:657.
- Miller DS, Blessing JA, Bodurka DC, et al. Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol 2008; 110:65.
- Lorusso D, Ferrandina G, Pignata S, et al. Evaluation of pemetrexed (Alimta, LY231514) as second-line chemotherapy in persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group. Ann Oncol 2010; 21:61.
- Thigpen T. The role of chemotherapy in the management of carcinoma of the cervix. Cancer J 2003; 9:425.
- Sutton GP, Blessing JA, DeMars LR, et al. A phase II Gynecologic Oncology Group trial of ifosfamide and mesna in advanced or recurrent adenocarcinoma of the endometrium. Gynecol Oncol 1996; 63:25.
- Bookman MA, Blessing JA, Hanjani P, et al. Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol 2000; 77:446.
- Muderspach LI, Blessing JA, Levenback C, Moore JL Jr. A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol 2001; 81:213.
- Abu-Rustum NR, Lee S, Massad LS. Topotecan for recurrent cervical cancer after platinum-based therapy. Int J Gynecol Cancer 2000; 10:285.
- Lhommé C, Fumoleau P, Fargeot P, et al. Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group phase II trial of first-line irinotecan in patients with advanced or recurrent squamous cell carcinoma of the cervix. J Clin Oncol 1999; 17:3136.
- Look KY, Blessing JA, Levenback C, et al. A phase II trial of CPT-11 in recurrent squamous carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol 1998; 70:334.
- Frenel JS, Le Tourneau C, O'Neil B, et al. Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial. J Clin Oncol 2017; 35:4035.
- Spanos W Jr, Guse C, Perez C, et al. Phase II study of multiple daily fractionations in the palliation of advanced pelvic malignancies: preliminary report of RTOG 8502. Int J Radiat Oncol Biol Phys 1989; 17:659.
- Onsrud M, Hagen B, Strickert T. 10-Gy single-fraction pelvic irradiation for palliation and life prolongation in patients with cancer of the cervix and corpus uteri. Gynecol Oncol 2001; 82:167.
- Halle JS, Rosenman JG, Varia MA, et al. 1000 cGy single dose palliation for advanced carcinoma of the cervix or endometrium. Int J Radiat Oncol Biol Phys 1986; 12:1947.
- van Lonkhuijzen L, Thomas G. Palliative radiotherapy for cervical carcinoma, a systematic review. Radiother Oncol 2011; 98:287.
- CLINICAL PRESENTATION
- DIAGNOSTIC EVALUATION
- MANAGEMENT OF LOCAL RECURRENCE
- Candidates for surgical resection
- - Surgical procedure
- Following RT with uterine conservation
- Following hysterectomy
- Nonsurgical options
- - Candidates for radiation therapy
- - Candidates for chemotherapy
- MANAGEMENT OF METASTATIC DISEASE
- Disease isolated to the lymph nodes
- Limited metastatic disease
- Metastatic disease
- - Chemotherapy plus bevacizumab as first-line treatment
- Combination chemotherapy
- Alternate use of carboplatin
- Combination versus single-agent therapy
- - Second-line therapy
- MANAGEMENT OF ACUTELY SYMPTOMATIC PATIENTS
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS