Key issues in the management of cervical cancer: consensus recommendations by a Brazilian expert panel

ABSTRACT

Objective: We report the results of a panel of Brazilian experts and provide recommendations for the management of these patients.

Material and Methods: The panel convened composed by 28 local opinion leaders, addressed 59 multiple-choice questions taking into account the published scientific literature and their own clinical experience. The level of agreement among panel members was qualified as (1) consensus, when at least 75% of the voting panel members; (2) majority vote (50%-74.9%); or (3) less than majority vote.

Results: There was at least majority vote for eight of 10 questions on staging and follow-up; for 14 of 23 questions on the treatment of early-stage disease; for 12 of 14 questions related to the treatment of locally-advanced disease; and for seven of the 12 questions related to the treatment of recurrent/metastatic disease. Conclusion: The current recommendations may help practitioners from Brazil and other countries to improve the care they provide to patients.

RESUMO

Objetivo: Relatamos os resultados de um painel de especialistas brasileiros e fornecemos recomendações para o manejo desses pacientes. Material e Métodos: O painel constituído por 28 formadores de opinião locais, abordou 59 questões de escolha múltipla tendo em conta a literatura científica publicada e a sua própria experiência clínica. O nível de concordância entre os membros do painel foi qualificado como: (1) consenso, quando pelo menos 75% dos membros do painel votaram; (2) voto majoritário (50%-74,9%); ou (3) menos do que a maioria dos votos. Resultados: Houve pelo menos maioria de votos para oito das 10 questões sobre estadiamento e acompanhamento; para 14 de 23 perguntas sobre o tratamento da doença em estágio inicial; para 12 das 14 questões relacionadas ao tratamento da doença localmente avançada; e para sete das 12 questões relacionadas ao tratamento da doença recorrente/metastática. Conclusão: As recomendações atuais podem ajudar profissionais do Brasil e de outros países a melhorar o atendimento que prestam aos pacientes.

Keywords:

Chemoradiotherapy - Gynecologic surgical procedures - Immune checkpoint inhibitors - Platinum compounds - Uterine cervical neoplasms

Descritores:

Quimiorradioterapia - Procedimentos cirúrgicos ginecológicos - Inibidores do checkpoint imunológico - Compostos de platina - Neoplasias do colo uterino

Publication History

Received: 27 December 2022

Accepted: 06 January 2023

Article published online:
02 February 2023

• REFERENCES

• 1 Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; May 71 (03) 209-49
• 2 Denny L, Sanjose S, Mutebi M, Anderson BO, Kim J, Jeronimo J. et al. Interventions to close the divide for women with breast and cervical cancer between low-income and middle-income countries and high-income countries. Lancet 2017; Feb 389 10071 861-70
• 3 Maza M, Schocken CM, Bergman KL, Randall TC, Cremer ML. Cervical precancer treatment in low- and middle- income countries: a technology overview. J Glob Oncol 2017; 3 (04) 400-8
• 4 Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; Mar 136 (05) E359-E86
• 5 Olson B, Gribble B, Dias J, Curryer C, Vo K, Kowal P. et al. Cervical cancer screening programs and guidelines in low- and middle-income countries. Int J Gynaecol Obstet 2016; Sep 134 (03) 239-46
• 6 Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Estimativa 2020: incidência de cancer no Brasil [Internet]. Rio de Janeiro: INCA; 2019. [access in 2022 Jan 11]. Available from https://www.inca.gov.br/sites/ufu.stunca.local/files/media/document/estimativa-2020-incidencia-de-cancer-no-brasil.pdf
• 7 Rodrigues AN, Melo AC, Calabrich AFC, Cronenberger E, Torres KL, Damian F. et al. Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215). Int J Gynecol Cancer 2022; 32 (02) 141-6
• 8 Paulino E, Melo AC, Silva-Filho AL, Maciel LF, Thuler LCS, Goss P. et al. Panorama of gynecologic cancer in Brazil. JCO Glob Oncol 2020; Oct 6: 1617-30
• 9 Peroni FMA, Lindelow M, Souza DO, Sjoblom M. Realizing the right to health in Brazil’s Unified Health System through the lens of breast and cervical cancer. Int J Equity Health 2019; Jun 18: 39
• 10 Oliveira MM, Andrade S, Oliveira PPV, Azevedo e Silva G, Silva MMA, Matal DC. Pap-test coverage in women aged 25 to 64 years old, according to the National Health Survey and the Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey, 2013. Rev Bras Epidemiol 2018; 21: e180014
• 11 Carvalho NP, Pilecco FB, Cherchiglia ML. Regional inequalities in cervical cancer survival in Minas Gerais State, Brazil. Cancer Epidemiol 2021; Apr 71 Pt A 101899
• 12 Dantas DB, Costa TL, Silva ASA, Gomes FC, Melo-Neto JS. Mortality from cervical cancer in Brazil: an ecological epidemiologic study of a 22-year analysis. Ecancermedicalscience 2020; 14: 1064
• 13 Oliveira NPD, Siqueira CADS, Lima KYN, Cancela MC, Souza DLB. Association of cervical and breast cancer mortality with socioeconomic indicators and availability of health services. Cancer Epidemiol 2020; Feb 64: 101660
• 14 Theme Filha MM, Leal MD, Oliveira EF, Esteves-Pereira AP, Gama SGN. Regional and social inequalities in the performance of Pap test and screening mammography and their correlation with lifestyle: Brazilian national health survey, 2013. Int J Equity Health 2016; 15: 136
• 15 Silva IF, Ferreira da Silva I, Koifman RJ. Cervical cancer treatment delays and associated factors in a cohort of women from a developing country. J Glob Oncol 2019; 5: 1-11
• 16 Ribeiro CM, Silva IS, Eluf Neto J, Cury LCPB, Azevedo e Silva G. Follow-up of women screened for cervical cancer in Sao Paulo, Brazil: An analysis of the times to diagnostic investigation and treatment. Cancer Epidemiol 2021; 72: 101940
• 17 Bhatla N, Berek JS, Fredes MC, Denny LA, Grenman S, Karunaratne K. et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet 2019; 145: 129-35
• 18 Cibula D, Potter R, Planchamp F, Avall-Lundqvist E, Fischerova D, Haie-Meder C. et al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer. Int J Gynecol Cancer 2018; Jun 28: 641-55
• 19 Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N. et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; Jul 28 Suppl 4 iv72-iv83
• 20 National Comprehensive Cancer Network (NCCN). NCCN Practice Guidelines in Oncology. Cervical Cancer – v.1.2022 [Internet] Plymouth Meeting: NCCN; 2022. [access in 2022 Jan 07]. Available from http://www.nccn.org
• 21 Elit L, Fyles AW, Devries MC, Oliver TK, Fung-Kee-Fung M. Gynecology Cancer Disease Site Group. Follow-up for women after treatment for cervical cancer: a systematic review. Gynecol Oncol 2009; Sep 114 (03) 528-35
• 22 Elit LM, Fyles AW, Gu CS, Pond GR, D’Souza D, Samant R. et al. Effect of positron emission tomography imaging in women with locally advanced cervical cancer: a randomized clinical trial. JAMA Netw Open 2018; Sep 1 (05) e182081
• 23 Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: a Gynecologic Oncology Group Study. Gynecol Oncol 1999; May 73 (02) 177-83
• 24 Peters WA, Liu PY, Barrett 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; Apr 18 (08) 1606-13
• 25 Cibula D, Abu-Rustum NR, Dusek L, Zikán M, Zaal A, Sevcik L. et al. Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer. Gynecol Oncol 2012; Mar 124 (03) 496-501
• 26 Cibula D, Kocian R, Plaikner A, Jarkovsky J, Klat J, Zapardiel I. et al. Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: the SENTIX trial. Eur J Cancer 2020; Sep 137: 69-80
• 27 Lecuru FR, McCormack M, Hillemanns P, Anota A, Leitao M, Mathevet P. et al. SENTICOL III: an international validation study of sentinel node biopsy in early cervical cancer. A GINECO, ENGOT, GCIG and multicenter study. Int J Gynecol Cancer 2019; May 29 (04) 829-34
• 28 Guani B, Mahiou K, Crestani A, Cibula D, Buda A, Gaillard T. et al. Clinical impact of low-volume lymph node metastases in early-stage cervical cancer: a comprehensive meta-analysis. Gynecol Oncol 2022; Feb 164 (02) 446-54
• 29 Guani B, Dorez M, Magaud L, Buenerd A, Lecuru F, Mathevet P. Impact of micrometastasis or isolated tumor cells on recurrence and survival in patients with early cervical cancer: SENTICOL Trial. Int J Gynecol Cancer 2019; Mar 29 (03) 447-52
• 30 Wenzel HHB, Smolders RGV, Beltman JJ, Lambrechts S, Trum HW, Yigit R. et al. Survival of patients with early-stage cervical cancer after abdominal or laparoscopic radical hysterectomy: a nationwide cohort study and literature review. Eur J Cancer 2020; Jul 133: 14-21
• 31 Melamed A, Margul DJ, Chen L, Keating NL, Del Carmen MG, Yang J. et al. Survival after minimally invasive radical hysterectomy for early-stage cervical cancer. N Engl J Med 2018; Nov 379: 1905-14
• 32 Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R. et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med 2018; Nov 379 (20) 1895-904
• 33 Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco K, Collingwood M. et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet 2001; Sep 358 (9284) 781-6
• 34 Xue R, Cai X, Xu H, Wu S, Haung H. The efficacy of concurrent weekly carboplatin with radiotherapy in the treatment of cervical cancer: a meta-analysis. Gynecol Oncol 2018; Sep 150 (03) 412-9
• 35 Dryden-Peterson S, Bvochora-Nsingo M, Suneja G, Efstathiou JA, Grover S, Chiyapo S. et al. HIV infection and survival among women with cervical cancer. J Clin Oncol 2016; Nov 34 (31) 3749-57
• 36 Ghebre RG, Grover S, Xu MJ, Chuang LT, Simonds H. Cervical cancer control in HIV-infected women: past, present and future. Gynecol Oncol Rep 2017; Jul 21: 101-8
• 37 Gupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Chopra SS. et al. Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIB squamous cervical cancer: a randomized controlled trial. J Clin Oncol 2018; Jun 36 (16) 1548-55
• 38 Sardain H, Lavoue V, Redpath M, Bertheuil N, Foucher F, Leveque J. Curative pelvic exenteration for recurrent cervical carcinoma in the era of concurrent chemotherapy and radiation therapy. A systematic review. Eur J Surg Oncol 2015; Aug 41 (08) 975-85
• 39 Pergialiotis V, Bellos I, Douligeris A, Thomakos N, Rodolakis A, Haidopoulos D. The impact of adjuvant hysterectomy on survival outcomes of patients with locally advanced cervical cancer: a network meta-analysis. Eur J Surg Oncol 2022; Jan 48 (01) 261-7
• 40 Horeweg N, Mittal P, Gradowska PL, Boere I, Chopra S, Nout RA. Adjuvant systemic therapy after chemoradiation and brachytherapy for locally advanced cervical cancer: a systematic review and meta-analysis. Cancers (Basel) 2021; Apr 13 (08) 1880
• 41 Kokka F, Bryant A, Brockbank E, Powell M, Oram D. Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer. Cochrane Database Syst Rev 2015; Apr 2015: CD010260
• 42 Simonds HM, Botha MH, Neugut AI, Van Der Merwe FH, Jacobson JS. Five-year overall survival following chemoradiation among HIV-positive and HIVnegative patients with locally advanced cervical carcinoma in a South African cohort. Gynecol Oncol 2018; Nov 151 (02) 215-20
• 43 Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R. et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med 2021; Nov 385 (20) 1856-67
• 44 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; Feb 370: 734-43
• 45 Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM. 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; Oct 390 10103 1654-63
• 46 Suzuki K, Nagao S, Shibutani T, Yamamoto K, Jimi T, Yano H. et al. Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancer. Gynecol Oncol 2019; Sep 154 (03) 554-7
• 47 KEYTRUDA® (pembrolizumab). Highlights of prescribing information [Internet]. New Jersey: Food and Drug Administration (FDA); 2021. [access in 2022 Jan 23]. Available from https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s096lbl.pdf
• 48 Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R. et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol 2019; Jun 37 (17) 1470-8
• 49 Frenel JS, Le Tourneau C, O’Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C. 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; Dec 35 (36) 4035-41
• 50 Rischin D, Gil-Martin M, Gonzalez-Martin A, Braña I, Hou JY, Cho D. et al. PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Gynecol Oncol 2020; Nov 159 (02) 322-8
• 51 Allen D, Narayan K. Managing advanced-stage cervical cancer. Best Pract Res Clin Obstet Gynaecol 2005; Aug 19 (04) 591-609
• 52 Ramondetta L. What is the appropriate approach to treating women with incurable cervical cancer?. J Natl Compr Canc Netw 2013; Mar 11 (03) 348-55
• 53 Maneo A, Landoni F, Cormio G, Colombo A, Placa F, Pellegrino A. et al. Concurrent carboplatin/5-fluorouracil and radiotherapy for recurrent cervical carcinoma. Ann Oncol 1999; Jul 10 (07) 803-7
• 54 Cerrotta A, Gardan G, Cavina R, Raspagliese F, Stefanon B, Garassino I. et al. Concurrent radiotherapy and weekly paclitaxel for locally advanced or recurrent squamous cell carcinoma of the uterine cervix. A pilot study with intensification of dose. Eur J Gynaecol Oncol 2002; 23 (02) 115-9
• 55 Windschall A, Ott OJ, Sauer R, Strnad V. Radiation therapy and simultaneous chemotherapy for recurrent cervical carcinoma. Strahlenther Onkol 2005; Aug 181 (08) 545-50
• 56 Mabuchi S, Matsumoto Y, Komura N, Sawada M, Tanaka M, Yokoi E. et al. The efficacy of surgical treatment of recurrent or persistent cervical cancer that develops in a previously irradiated field: a monoinstitutional experience. Int J Clin Oncol 2017; Oct 22 (05) 927-36
• 57 Rema P, Mathew AP, Suchetha S, Ahmed I. Salvage surgery for cervical cancer recurrences. Indian J Surg Oncol 2017; Jun 8 (02) 146-9
• 58 Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N. et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018; 29: iv262
• 59 Carlson RW, Larsen JK, McClure J, Fitzgerald CL, Venook AP, Benson AB. et al. International adaptations of NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2014; May 12 (05) 643-8
• 60 Chopra SJ, Mathew A, Maheshwari A, Bhatla N, Singh S, Rai B. et al. National Cancer Grid of India Consensus Guidelines on the Management of Cervical Cancer. J Glob Oncol 2018; Jul 4: 1-15
• 61 Chuang LT, Temin S, Camacho R, Dueñas-Gonzales A, Feldman S, Gultekin M. et al. Management and care of women with invasive cervical cancer: American Society of Clinical Oncology resource-stratified clinical practice guideline. J Glob Oncol 2016; Oct 2 (05) 311-40
• 62 Jazieh AR, Azim HA, McClure J, Jahanzeb M. The process of NCCN guidelines adaptation to the Middle East and North Africa region. J Natl Compr Canc Netw 2010; Jul 8 Suppl 3 S5-7
• 63 Akaza H. What is the Asian Consensus Statement on NCCN clinical practice guidelines in oncology (NCCN-ACS)?. Jpn J Clin Oncol 2016; Apr 46 (04) 299-302