Adenocarcinoma of the Cervix: Should We Treat It Differently?

Current Oncology Reports

Volumn 17, Issue 4, 2015, Pages

  Williams, Ned L ^a   Werner, Theresa L ^a   Jarboe, Elke A ^a   Gaffney, David K ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Adenocarcinoma; Cervical; Cervix; Difference; Squamous cell carcinoma; Treatment

Indexed keywords

BEVACIZUMAB; BLEOMYCIN; CARBOPLATIN; CISPLATIN; DOXORUBICIN; FLUOROURACIL; IRINOTECAN; METHOTREXATE; MITOMYCIN; VINBLASTINE;

ADENOCARCINOMA; BRACHYTHERAPY; CANCER ADJUVANT THERAPY; CHEMORADIOTHERAPY; DIFFERENTIAL DIAGNOSIS; DISEASE FREE SURVIVAL; ENDOMETRIUM BIOPSY; HUMAN; OVERALL SURVIVAL; PROGRESSION FREE SURVIVAL; RADICAL HYSTERECTOMY; REVIEW; UTERINE CERVIX ADENOCARCINOMA; UTERINE CERVIX BIOPSY; UTERINE CERVIX CARCINOMA; CANCER STAGING; COMPLICATION; EARLY DIAGNOSIS; FEMALE; PAPILLOMAVIRUS INFECTIONS; PATHOLOGY; PROGNOSIS; UTERINE CERVICAL NEOPLASMS; VIROLOGY;

ADENOCARCINOMA; DISEASE-FREE SURVIVAL; EARLY DETECTION OF CANCER; FEMALE; HUMANS; NEOPLASM STAGING; PAPILLOMAVIRUS INFECTIONS; PROGNOSIS; UTERINE CERVICAL NEOPLASMS;

EID: 84923658782     PISSN: 15233790     EISSN: 15346269     Source Type: Journal    
DOI: 10.1007/s11912-015-0440-6     Document Type: Review

References (87)

1. GLOBOCAN 2012: Estimated cervical cancer incidence, mortality and prevalence worldwide in 2012. International Agency for Research on Cancer. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics. CA Cancer J Clin. 2014;64:9–29.
3. American Cancer Society. Cancer facts and figures 2014. Atlanta: American Cancer Society; 2014.
4. Adegoke O, Kulasingam S, Virnig B. Cervical cancer trends in the United States: a 35-year population-based analysis. J Womens Health (Larchmt). 2012;21(10):1031–7.
5. National Cancer Institute: SEER Stat Fact Sheets. http://seer.cancer.gov/statfacts/html/cervix.html.
6. Alfsen GC, Thoresen SO, Kristensen GB, Skovlund E, Abeler VM. Histopathologic subtyping of cervical adenocarcinoma reveals increasing incidence rates of endometrioid tumors in all age groups: a population based study with review of all nonsquamous cervical carcinomas in Norway from 1966 to 1970, 1976 to 1980, and 1986 to 1990. Cancer. 2000;89(6):1291.
7. Rodríguez AC, Schiffman M, Herrero R, Wacholder S, Hildesheim A, Castle PE, et al. Proyecto Epidemiológico Guanacaste Group. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst. 2008;100(7):513–7. 2008.
8. Brisson J, Morin C, Fortier M, Roy M, Bouchard C, Leclerc J, et al. Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions. Am J Epidemiol. 1994;140(8):700–10.
9. Muñoz N, Franceschi S, Bosetti C, Moreno V, Herrero R, Smith JS, et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet. 2002;359(9312):1093–101.
10. Moreno V, Bosch FX, Muñoz N, Meijer CJ, Shah KV, Walboomers JM, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet. 2002;359(9312):1085–92.
11. Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variation by geographical region, histological type and year of publication. Int J Cancer. 2011;128(4):927–35.
12. Castellsagué X, Díaz M, de Sanjosé S, Muñoz N, Herrero R, Franceschi S, et al. International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst. 2006;98:303–15.
13. International Collaboration of Epidemiological Studies of Cervical Cancer. Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer. 2006;118:1481–95.
14. Bosch FX, de Sanjosé S. Chapter 1: human papillomavirus and cervical cancer—burden and assessment of causality. J Natl Cancer Inst Monogr. 2003;31:3–13.
15. Chen RJ, Lin YH, Chen CA, Huang SC, Chow SN, Hsieh CY. Influence of histologic type and age on survival rates for invasive cervical carcinoma in Taiwan. Gynecol Oncol. 1999;73:184–90.
16. Hopkins MP, Morley GW. A comparison of adenocarcinoma and squamous cell carcinoma of the cervix. Obstet Gynecol. 1991;77:912–7.
17. Eifel PJ, Morris M, Oswald MJ, Wharton JT, Delclos L. Adenocarcinoma of the uterine cervix. Prognosis and patterns of failure in 367 cases. Cancer. 1990;65(11):2507.
18. Eifel PJ, Burke TW, Morris M, Smith TL. Adenocarcinoma as an independent risk factor for desease recurrence in patients with stage IB cervical carcinoma. Gynecol Oncol. 1995;59(1):38–44.
19. Kilgore LC, Soong SJ, Gore H, Shingleton HM, Hatch KD, Partridge EE. Analysis of prognostic features in adenocarcinoma of the cervix. Gynecol Oncol. 1988;31(1):137.
20. Baalbergen A, Ewing-Grahamb PC, Hopc WCJ, Struijkd P, Helmerhorstd TJM. Prognostic factors in adenocarcinoma of the uterine cervix. Gynecol Oncol. 2004;92(1):262–7.
21. Rose PG, Java JJ, Whitney CW, Stehman FB, Lanciano R, Thomas GM. Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in Gynecologic Oncology Group trials of cisplatin-based CCRT. Gynecol Oncol. 2014. A retrospective review of 1,671 patients (182 AC/ASC, 1489 SCC) previously enrolled in GOG trials, assessing outcome by histology. The key findings are: AC/ASC have poorer OS when treated with RT alone (p = 0.0499); Similar OS when treated with chemoRT regimen containing cisplatin (p = 0.459).
22. Shimada M, Kigawa J, Nishimura R, Yamaguchi S, Kuzuya K, Nakanishi T, et al. Ovarian metastasis in carcinoma of the uterine cervix. Gynecol Oncol. 2006;101(2):234–7.
23. Irie T, Kigawa J, Minagawa Y, Itamochi H, Sato S, Akeshima R, et al. Prognosis and clinicopathological characteristics of Ib-IIb adenocarcinoma of the uterine cervix in patients who have had radical hysterectomy. Eur J Surg Oncol. 2000;26(5):464–7.
24. Katanyoo K, Sanguanrungsirikul S, Manusirivithaya S. Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer. Gynecol Oncol. 2012;125(2):292.
25. Galic V, Herzog TJ, Lewin SN, Neugut AI, Burke WM, Lu YS, et al. Prognostic significance of adenocarcinoma histology in women with cervical cancer. Gynecol Oncol. 2012;125(2):287.
26. Macdonald OK, Chen J, Dodson M, Lee CM, Gaffney DK. Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix. Am J Clin Oncol. 2009;32(4):411–6.
27. Davy ML, Dodd TJ, Luke CG, Roder DM. Cervical cancer: effect of glandular cell type on prognosis, treatment, and survival. Obstet Gynecol. 2003;101(1):38–45.
28. Lee YY, Choi CH, Kim TJ, Lee JW, Kim BG, Lee JH, et al. A comparison of pure adenocarcinoma and squamous cell carcinoma of the cervix after radical hysterectomy in stage IB-IIA. Gynecol Oncol. 2011;120(3):439.
29. Park JY, Kim DY, Kim JH, Kim YM, Kim YT, Nam JH. Outcomes after radical hysterectomy in patients with early-stage adenocarcinoma of uterine cervix. Br J Cancer. 2010;102(12):1692–8.
30. Berek JS, Hacker NS, Fu YS, et al. Adenocarcinoma of the uterine cervix: histologic variables associated with lymph node metastasis and survival. Obstet Gynecol. 1985;65:46–52.
31. Kleine W, Rau K, Schwoeorer D, Pfleiderer A. Prognosis of adenocarcinoma of the cervix uteri: a comparative study. Gynecol Oncol. 1989;35:145–59.
32. Nakanishi T, Ishikawa H, Suzuki Y, Inoue T, Nakamura S, Kuzuya K. A comparison of prognoses of pathologic stage IB adenocarcinoma and squamous cell carcinoma of the uterine cervix. Gynecol Oncol. 2000;79:289–93.
33. McCluggage WG, Sumathi VP, McBride HA, Patterson A. A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids in the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol. 2002;21(1):11–5.
34. Staebler A, Sherman ME, Zaino RJ, Ronnett BM. Hormone receptor immunohistochemistry and human papillomavirus in situ hybridization are useful for distinguishing endocervical and endometrial adenocarcinomas. Am J Surg Pathol. 2002;26(8):998–1006.
35. McCluggage WG, Jenkins D. p16 immunoreactivity may assist in the distinction between endometrial and endocervical adenocarcinoma. Int J Gynecol Pathol. 2003;22(3):231–5.
36. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9.
37. Prevention of Genital HPV Infection and Sequelae: Report of an External Consultants’ Meeting. Atlanta, GA: Centers for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention, 1999. Web. http://www.cdc.gov/std/hpv/HPVSupplement99.pdf.
38. Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16(1):1–17.
39. Castellsagué X, Díaz M, Sanjosé S, Muñoz N, Herrero R, Franceschi S, et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst. 2006;98(5):303–15.
40. Junior JE, Giraldo PC, Gonçalves AK, do Amaral RL, Linhares IM. Uterine cervical ectopy during reproductive age: cytological and microbiological findings. Diagn Cytopathol. 2014;42(5):401–4.
41. Andersson S, Rylander E, Larsson B, Strand A, Silfversvärd C, Wilander E. The role of human papillomavirus in cervical adenocarcinoma carcinogenesis. Eur J Cancer. 2001;37(2):246–50.
42. Moscicki AB, Hills N, Shiboski S, Powell K, Jay N, Hanson E, et al. Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females. JAMA. 2001;285(23):2995–3002.
43. Woodman CB, Collins S, Winter H, Bailey A, Ellis J, Prior P, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet. 2001;357(9271):1831–6.
44. Elfgren K, Kalantari M, Moberger B, Hagmar B, Dillner J. A population-based 5-year follow-up study of cervical human papillomavirus infection. Am J Obstet Gynecol. 2000;183:561–7.
45. Schlecht NF, Kulaga S, Robitaille J, Ferreira S, Santos M, Miyamura RA, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA. 2001;286:3106–14.
46. Koshiol J, Lindsay L, Pimenta JM, Poole C, Jenkins D, Smith JS. Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis. Am J Epidemiol. 2008;168(2):123–37.
47. Chen HC, Schiffman M, Lin CY, Pan MH, You SL, Chuang LC, et al. Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer. J Natl Cancer Inst. 2011;103(18):1387–96.
48. Smith JS, Herrero R, Bosetti C, Muñoz N, Bosch FX, Eluf-Neto J, et al. International Agency for Research on Cancer (IARC) Multicentric Cervical Cancer Study Group. Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst. 2002;94:1604–13.
49. Smith JS, Bosetti C, Muñoz N, Herrero R, Bosch FX, Eluf-Neto J, et al. IARC multicentric case-control study. Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer. 2004;111:431–9.
50. Garcia-Closas R, Castellsague X, Bosch X, Gonzalez CA. The role of diet and nutrition in cervical carcinogenesis: a review of recent evidence. Int J Cancer. 2005;117(4):629–37.
51. Carrillo-García A, Ponce-de-León-Rosales S, Cantú-de-León D, Fragoso-Ontiveros V, Martínez-Ramírez I, Orozco-Colín A, et al. Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer. Gynecol Oncol. 2014;134(3):534–9.
52. Kjær 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(19):1478–88.
53. Vink MA, Bogaards JA, van Kemenade FJ, de Melker HE, Meijer CJ, Berkhof J. Clinical progression of high-grade cervical intraepithelial neoplasia: estimating the time to preclinical cervical cancer from doubly censored national registry data. Am J Epidemiol. 2013;178(7):1161–9.
54. Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy for locally advanced cervical cancer: a systematic review and meta-analysis of individual patient data from 21 randomised trials. Eur J Cancer. 2003;39(17):2470–86.
55. Rydzewska L, Tierney J, Vale CL, Symonds PR. Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer. Cochrane Database Syst Rev. 2012;12:CD007406.
56. Kim HS, Sardi JE, Katsumata N, Ryu HS, Nam JH, Chung HH, et al. Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-analysis. Eur J Surg Oncol. 2013;39(2):115–24.
57. Kim HS, Kim JY, Park NH, Kim K, Chung HH, Kim YB, et al. Matched-case comparison for the efficacy of neoadjuvant chemotherapy before surgery in FIGO stage IB1-IIA cervical cancer. Gynecol Oncol. 2010;119(2):217–24.
58. Kumar L, Kaushal R, Nandy M, Biswal BM, Kumar S, Kriplani A, et al. Chemotherapy followed by radiotherapy versus radiotherapy alone in locally advanced cervical cancer: a randomized study. Gynecol Oncol. 1994;54(3):307–15.
59. He L, Wu L, Su G, Wei W, Liang L, Han L, et al. The efficacy of neoadjuvant chemotherapy in different histological types of cervical cancer. Gynecol Oncol. 2014;134(2):419–25. The key findings were: No difference between non-SCC and SCC in short term efficacy or clinical response to NAC (p = 0.29); Significantly improved long-term survival of SCC compared to non-SCC (HR = 1.47).
60. Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet. 1997;350(9077):535–40.
61. Keys HM, Bundy BN, Stehman FB, Okagaki T, Gallup DG, Burnett AF, et al. Radiation therapy with and without extrafascial hysterectomy for bulky stage IB cervical carcinoma: a randomized trial of the Gynecologic Oncology Group. Gynecol Oncol. 2003;89(3):343–53.
62. Ota T, Takeshima N, Tabata T, Hasumi K, Takizawa. Adjuvant hysterectomy for treatment of residual disease in patients with cervical cancer treated with radiation therapy. Br J Cancer. 2008;99(8):1216–20.
63. Shoji T, Kumagai S, Yoshizaki A, Yokoyama Y, Fujimoto T, Takano T, et al. Efficacy of neoadjuvant chemotherapy followed by radical hysterectomy in locally advanced non-squamous carcinoma of the uterine cervix: a retrospective multicenter study of Tohoku Gynecologic Cancer Unit. Eur J Gynaecol Oncol. 2012;33(4):353–7.
64. Colombo N, Carinelli S, Colombo A, Marini C, Rollo D, Sessa C. Cervical cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii27–32.
65. Houvenaeghel G, Lelievre L, Gonzague-Casabianca L, Buttarelli M, Moutardier V, Goncalves A, et al. Long-term survival after concomitant chemoradiotherapy prior to surgery in advanced cervical carcinoma. Gynecol Oncol. 2006;100(2):338–43.
66. Ferrandina G, Legge F, Fagotti A, Fanfani F, Distefano M, Morganti A, et al. Preoperative concomitant chemoradiotherapy in locally advanced cervical cancer: safety, outcome, and prognostic measures. Gynecol Oncol. 2007;107(1 Suppl 1):S127–32.
67. Classe JM, Rauch P, Rodier JF, Morice P, Stoeckle E, Lasry S, et al. Surgery after concurrent chemoradiotherapy and brachytherapy for the treatment of advanced cervical cancer: morbidity and outcome: results of a multicenter study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer). Gynecol Oncol. 2006;102(3):523–9.
68. Lerouge D, Touboul E, Lefranc JP, Uzan S, Jannet D, Moureau-Zabotto L, et al. Preoperative concurrent radiation therapy and chemotherapy for operable bulky carcinomas of uterine cervix stages IB2, IIA, and IIB with proximal parametrial invasion. Cancer Radiother. 2004;8(3):168–77.
69. Azria E, Morice P, Haie-Meder C, Thoury A, Pautier P, Lhomme C, et al. Results of hysterectomy in patients with bulky residual disease at the end of chemoradiotherapy for stage IB2/II cervical carcinoma. Ann Surg Oncol. 2005;12(4):332–7.
70. Darus CJ, Callahan MB, Nguyen QN, Pastore LM, Schneider BF, Rice LW, et al. Chemoradiation with and without adjuvant extrafascial hysterectomy for IB2 cervical carcinoma. Int J Gynecol Cancer. 2008;18(4):730–5.
71. Colombo PE, Bertrand MM, Gutowski M, Mourregot A, Fabbro M, Saint-Aubert B, et al. Total laparoscopic radical hysterectomy for locally advanced cervical carcinoma (stages IIB, IIA and bulky stages IB) after concurrent chemoradiation therapy: surgical morbidity and oncological results. Gynecol Oncol. 2009;114(3):404–9.
72. Huguet F, Cojocariu OM, Levy P, Lefranc JP, Darai E, Jannet D, et al. Preoperative concurrent radiation therapy and chemotherapy for bulky stage IB2, IIA, and IIB carcinoma of the uterine cervix with proximal parametrial invasion. Int J Radiat Oncol Biol Phys. 2008;72(5):1508–15.
73. Morice P, Uzan C, Zafrani Y, Delpech Y, Gouy S, Haie-Meder C. The role of surgery after chemoradiation therapy and brachytherapy for stage IB2/II cervical cancer. Gynecol Oncol. 2007;107(1 Suppl 1):S122–4.
74. Sarraf Z, Hamedi B, Hooshmand S, Mosalaie A, Robati M, Momtahan M, et al. The effect of extrafascial hysterectomy after completion of external beam radiotherapy for treatment of locally advanced stages (IIB-III) of cervical cancer. Iran Red Crescent Med J. 2013;15(12):e10758.
75. Fröbe A, Jones G, Bokulić T, Mrčela I, Budanec M, Murgić J, et al. High-dose-rate brachytherapy and concurrent chemoradiotherapy followed by surgery for stage Ib-IIb cervical cancer: single institution experience. Anticancer Res. 2014;34(7):3861–6.
76. Morice P, Rouanet P, Rey A, Romestaing P, Houvenaeghel G, Boulanger JC, et al. Results of the GYNECO 02 study, an FNCLCC phase III trial comparing hysterectomy with no hysterectomy in patients with a (clinical and radiological) complete response after chemoradiation therapy for stage IB2 or II cervical cancer. Oncologist. 2012;17(1):64–71.
77. NCCN Clinical Practice Guidelines: Cervical Cancer, Version 2.2015, 18 Sep. 2014. National Comprehensive Cancer Network, Inc. http://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf
78. “NCI Issues Announcement on Cervical Cancer.” National Cancer Institute. National Cancer Institute, 22 Feb. 1999. http://www.cancer.gov/newscenter/newsfromnci/1999/cervicalcancer.
79. Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999;17(5):1339–48.
80. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340(15):1144–53.
81. Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs 3rd CL, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999;340(15):1154–61.
82. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340(15):1137–43.
83. Peters 3rd WA, Liu PY, Barrett 2nd RJ, 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(8):1606–13.
84. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008;26(35):5802–12.
85. Monk BJ, Sill MW, McMeekin DS, Cohn DE, Ramondetta LM, Boardman CH, 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(28):4649–55.
86. Moore KN, Herzog TJ, Lewin S, Giuntoli RL, Armstrong DK, Rocconi RP, et al. A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol Oncol. 2007;105(2):299–303.
87. Tewari KS, Sill MW, Long HJ, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370(8):734–43. A RCT of 452 patients with metastatic, recurrent, or persistent ICC, randomized to chemotherapy or chemotherapy plus bevacizumab. Bevacizumab increased OS (p = 0.004) and response rates (p = 0.008). Bavacizumab also increased toxicity ≥ grade 2 HTN, ≥ grade 3 thromboembolic events, ≥ grade 3 GI fistula formation.