Introduction: In Madagascar, cervical cancer ranks second among cancer pathologies after breast cancer. It is diagnosed at a locally advanced stage in 79% of cases, where chemoradiotherapy followed by brachytherapy is the standard treatment. In the absence of brachytherapy, our objectives were to describe the evolution of locally advanced cervical cancers treated with chemoradiotherapy and to identify prognostic factors for progression and recurrence. Materials and Methods: This was a retrospective study including cervical cancers from stage IB3 to IVA between January 1, 2020, and December 30, 2021, at the Radiotherapy Department of the Joseph Ravoahangy Andrianavalona University Hospital. The median follow-up time was 15 months. Kaplan Meier analysis was used for disease-free survival. Proportion comparisons were made using the log-rank test and Cox model. Results: We collected data from 64 patients. The remission rate was 51.5% compared to a 48.4% therapeutic failure rate, of which 34.3% was progression and 14% was recurrence. The median time to progression and recurrence was 4 months and 8 months, respectively. The 15-month recurrence-free survival rate was 50%. Fixation to the pelvic wall (p = 0.0001), pelvic and/or lomboaortic lymph node involvement (p = 0.03), and stage (p = 0.001) were significantly associated with the occurrence of therapeutic failure. Conclusion: The prognosis for locally advanced cervical cancers is reserved, largely explained by the very advanced stage of the disease. To improve the therapeutic index, efforts should focus on prevention, and access to brachytherapy equipment is essential.
References
[1]
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. https://doi.org/10.3322/caac.21492
[2]
Arbyn, M., Weiderpass, E., Bruni, L., de Sanjosé, S., Saraiya, M., Ferlay, J., et al. (2020) Estimates of Incidence and Mortality of Cervical Cancer in 2018: A Worldwide Analysis. The Lancet Global Health, 8, e191-e203. https://doi.org/10.1016/s2214-109x(19)30482-6
[3]
Lahimalaza, T.F.L. (2024) Épidémiologie descriptive des cancers dans les centres de cancérologie de madagascar. Antananarivo, Médecine humaine.
[4]
Hasiniatsy, N.R.E., Ernestho-ghoud, I.M., Ralamboson, S.A., Rabarijaona, L.I. and Rafaramino, F. (2014) Prise en charge et suivi des cancers du col utérin: La réalité à Antananarivo, Madagascar. Journal Africain du Cancer/African Journal of Cancer, 6, 40-46. https://doi.org/10.1007/s12558-014-0308-3
[5]
Association d’appui à la Radiothérapie et l’Oncologie de Madagascar (2018) XVIIèmes journées de cancérologie de Madagascar “Epidémiologie des cancers à Madagascar”. Revue Malgache de Cancérologie, 3, 93-115.
[6]
Hasiniatsy, N.R.E. (2008) Evolution des aspects épidemio-clinico-thérapeutiques du cancer du col utérin au service oncologie HJRA. Antananarivo. Médecine humaine.
[7]
Charra-Brunaud, C., Salleron, J., Menoux, I., Peignaux, K., Ducassou, A., Petit, A., et al. (2022) Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués: Résultats finaux du PHRC Tridicol. Cancer/Radiothérapie, 26, 474-480. https://doi.org/10.1016/j.canrad.2021.06.030
[8]
Tan, L., Tanderup, K., Kirisits, C., Mahantshetty, U., Swamidas, J., Jürgenliemk-Schulz, I., et al. (2020) Education and Training for Image-Guided Adaptive Brachytherapy for Cervix Cancer—The (GEC)-ESTRO/EMBRACE Perspective. Brachytherapy, 19, 827-836. https://doi.org/10.1016/j.brachy.2020.06.012
[9]
Chargari, C., Renard, S., Espenel, S., Escande, A., Buchheit, I., Ducassou, A., et al. (2020) La radiothérapie stéréotaxique peut-elle remplacer la curiethérapie pour les cancers du col utérin localement évolués? Positionnement de la Société française de radiothérapie oncologique. Cancer/Radiothérapie, 24, 706-713. https://doi.org/10.1016/j.canrad.2020.05.003
[10]
Errachdi, A., Asabbane, A., Nkoua Epala, B., Hemmich, M., Kabbali, N., Kebdani, T., et al. (2014) Cancer avancé du col utérin: Aspects évolutif et pronostique. Expérience marocaine. La Presse Médicale, 43, e257-e264. https://doi.org/10.1016/j.lpm.2014.02.029
[11]
Bourgin, C., Estevez, J.P. and Collinet, P. (2018) Surveillance post-thérapeutique des cancers du col en France: Priorité à l’examen clinique. Gynécologie Obstétrique Fertilité & Sénologie, 46, 503-505. https://doi.org/10.1016/j.gofs.2018.03.004
[12]
Cao, K.I., Mazeron, R. and Barillot, I. (2015) Suivi après radiothérapie pour un cancer du col utérin. Cancer/Radiothérapie, 19, 590-596. https://doi.org/10.1016/j.canrad.2015.05.005
[13]
Marchal, C., Rangeard, L. and Brunaud, C. (2005) Impact de l’anémie sur les traitements des cancers du col utérin. Cancer/Radiothérapie, 9, 87-95. https://doi.org/10.1016/j.canrad.2005.01.004
Yeung, A.R., Amdur, R.J., Morris, C.G., Morgan, L.S. and Mendenhall, W.M. (2007) Long-Term Outcome after Radiotherapy for FIGO Stage IIIB and IVA Carcinoma of the Cervix. International Journal of Radiation Oncology∙Biology∙Physics, 67, 1445-1450. https://doi.org/10.1016/j.ijrobp.2006.11.013
[16]
Kesic, V. (2006) Management of Cervical Cancer. European Journal of Surgical Oncology, 32, 832-837. https://doi.org/10.1016/j.ejso.2006.03.037
[17]
Randriamanovontsoa, N.E. (2010) Radiochimiothérapie concomitante du cancer du col utérin au service oncologie-radiothérapie CHU/HJRA 2007-2009. Antananarivo. Médecine humaine.
[18]
Perez, C.A., Grigsby, P.W., Chao, K.S.C., Mutch, D.G. and Lockett, M.A. (1998) Tumor Size, Irradiation Dose, and Long-Term Outcome of Carcinoma of Uterine Cervix. International Journal of Radiation Oncology∙Biology∙Physics, 41, 307-317. https://doi.org/10.1016/s0360-3016(98)00067-4
[19]
Ulmer, H.U. and Frischbier, H.-. (1983) Treatment of Advanced Cancers of the Cervix Uteri with External Irradiation Alone. International Journal of Radiation Oncology∙Biology∙Physics, 9, 809-812. https://doi.org/10.1016/0360-3016(83)90005-6
[20]
Girinski, T., Pejovic-Lenfant, M.H., Bourhis, J., Campana, F., Cosset, J.M., Petit, C., et al. (1989) Prognostic Value of Hemoglobin Concentrations and Blood Transfusions in Advanced Carcinoma of the Cervix Treated by Radiation Therapy: Results of a Retrospective Study of 386 Patients. International Journal of Radiation Oncology∙Biology∙Physics, 16, 37-42. https://doi.org/10.1016/0360-3016(89)90007-2
[21]
Nguyen, D., de la Rochefordière, A., Chauveinc, L., Cosset, J.M., Clough, K.B., Beuzeboc, P., et al. (2002) Chimioradiothérapie dans les cancers du col utérin localement évolués. Étude rétrospective de 92 patientes traitées à l’institut Curie de 1986 à 1998. Cancer/Radiothérapie, 6, 201-208. https://doi.org/10.1016/s1278-3218(02)00196-8
[22]
Hirakawa, M., Nagai, Y., Inamine, M., Kamiyama, K., Ogawa, K., Toita, T., et al. (2008) Predictive Factor of Distant Recurrence in Locally Advanced Squamous Cell Carcinoma of the Cervix Treated with Concurrent Chemoradiotherapy. Gynecologic Oncology, 108, 126-129. https://doi.org/10.1016/j.ygyno.2007.08.091
[23]
Hong, J., Tsai, C., Lai, C., Chang, T., Wang, C., Chou, H., et al. (2004) Recurrent Squamous Cell Carcinoma of Cervix after Definitive Radiotherapy. International Journal of Radiation Oncology∙Biology∙Physics, 60, 249-257. https://doi.org/10.1016/j.ijrobp.2004.02.044
[24]
Pathy, S., Muwonge, R., Chander, S., Dadhwal, V. and Pandjatcharam, J. (2014) Predictors of Tumor Response in Carcinoma of Uterine Cervix: Data from Tertiary Cancer Centre in India. Bulletin du Cancer, 101, E13-E18. https://doi.org/10.1684/bdc.2014.1895
[25]
Sirák, I., Petera, J. and Zoul, Z. (2008) The Influence of Cisplatin Dose Upon Survival in Concurrent Chemoradiotherapy of Locally Advanced Cervical Carcinoma with Weekly Cisplatin. Acta Medica (Hradec Kralove, Czech Republic), 51, 95-99. https://doi.org/10.14712/18059694.2017.9
[26]
Nugent, E.K., Case, A.S., Hoff, J.T., Zighelboim, I., DeWitt, L.L., Trinkhaus, K., et al. (2010) Chemoradiation in Locally Advanced Cervical Carcinoma: An Analysis of Cisplatin Dosing and Other Clinical Prognostic Factors. Gynecologic Oncology, 116, 438-441. https://doi.org/10.1016/j.ygyno.2009.09.045
[27]
Katanyoo, K., Sanguanrungsirikul, S. and Manusirivithaya, S. (2012) Comparison of Treatment Outcomes between Squamous Cell Carcinoma and Adenocarcinoma in Locally Advanced Cervical Cancer. Gynecologic Oncology, 125, 292-296. https://doi.org/10.1016/j.ygyno.2012.01.034
[28]
Khayat, D. (2020) Influence de l’étalement de la radiothérapie sur le pronostic du cancer du col utérin. Marrakech, Médecine humaine.
[29]
Chao, K.S.C., Williamson, J.F., Grigsby, P.W. and Perez, C.A. (1998) Uterosacral Space Involvement in Locally Advanced Carcinoma of the Uterine Cervix. International Journal of Radiation Oncology∙Biology∙Physics, 40, 397-403. https://doi.org/10.1016/s0360-3016(97)00577-4
[30]
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration (2008) Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. Journal of Clinical Oncology, 26, 5802-5812. https://doi.org/10.1200/JCO.2008.16.4368
[31]
Fyles, A.W., Pintilie, M., Kirkbride, P., Levin, W., Manchul, L.A. and Rawlings, G.A. (1995) Prognostic Factors in Patients with Cervix Cancer Treated by Radiation Therapy: Results of a Multiple Regression Analysis. Radiotherapy and Oncology, 35, 107-117. https://doi.org/10.1016/0167-8140(95)01535-o
[32]
Saibishkumar, E.P., Patel, F.D., Sharma, S.C., Karunanidhi, G., Ghoshal, S., Kumar, V., et al. (2006) Prognostic Value of Response to External Radiation in Stage IIIB Cancer Cervix in Predicting Clinical Outcomes: A Retrospective Analysis of 556 Patients from India. Radiotherapy and Oncology, 79, 142-146. https://doi.org/10.1016/j.radonc.2006.03.016
[33]
Ferrigno, R., Campos de Oliveira Faria, S.L., Weltman, E., Salvajoli, J.V., Segreto, R.A., Pastore, A., et al. (2003) Radiotherapy Alone in the Treatment of Uterine Cervix Cancer with Telecobalt and Low-Dose-Rate Brachytherapy: Retrospective Analysis of Results and Variables. International Journal of Radiation Oncology∙Biology∙Physics, 55, 695-706. https://doi.org/10.1016/s0360-3016(02)03939-1
[34]
Rutledge, F.N., Mitchell, M.F., Munsell, M., Bass, S., McGuffee, V. and Atkinson, E.N. (1992) Youth as a Prognostic Factor in Carcinoma of the Cervix: A Matched Analysis. Gynecologic Oncology, 44, 123-130. https://doi.org/10.1016/0090-8258(92)90027-g
[35]
Serur, E., Fruchter, R.G., Maiman, M., McGuire, J., Arrastia, C.D. and Gibbon, D. (1995) Age, Substance Abuse, and Survival of Patients with Cervical Carcinoma. Cancer, 75, 2530-2538. https://doi.org/10.1002/1097-0142(19950515)75:10<2530::aid-cncr2820751020>3.0.co;2-i
[36]
Grogan, M., Thomas, G.M., Melamed, I., Wong, F.L.W., Pearcey, R.G., Joseph, P.K., et al. (1999) The Importance of Hemoglobin Levels during Radiotherapy for Carcinoma of the Cervix. Cancer, 86, 1528-1536. https://doi.org/10.1002/(sici)1097-0142(19991015)86:8<1528::aid-cncr20>3.0.co;2-e
[37]
Bush, R.S. (1986) The Significance of Anemia in Clinical Radiation Therapy. International Journal of Radiation Oncology*Biology*Physics, 12, 2047-2050. https://doi.org/10.1016/0360-3016(86)90146-x
[38]
Eifel, P.J., Burke, T.W., Morris, M. and Smith, T.L. (1995) Adenocarcinoma as an Independent Risk Factor for Disease Recurrence in Patients with Stage IB Cervical Carcinoma. Gynecologic Oncology, 59, 38-44. https://doi.org/10.1006/gyno.1995.1265
[39]
Monk, B.J., Wang, J., Im, S., Stock, R.J., Peters, W.A., Liu, P.Y., et al. (2005) Rethinking the Use of Radiation and Chemotherapy after Radical Hysterectomy: A Clinical-Pathologic Analysis of a Gynecologic Oncology Group/Southwest Oncology Group/radiation Therapy Oncology Group Trial. Gynecologic Oncology, 96, 721-728. https://doi.org/10.1016/j.ygyno.2004.11.007
[40]
Balaya, V., Guani, B., Magaud, L., Bonsang-Kitzis, H., Ngô, C., Mathevet, P., et al. (2020) Validation of the 2018 FIGO Classification for Cervical Cancer: Lymphovascular Space Invasion Should Be Considered in IB1 Stage. Cancers, 12, Article 3554. https://doi.org/10.3390/cancers12123554
[41]
Lanciano, R.M., Won, M., Coia, L.R. and Hanks, G.E. (1991) Pretreatment and Treatment Factors Associated with Improved Outcome in Squamous Cell Carcinoma of the Uterine Cervix: A Final Report of the 1973 and 1978 Patterns of Care Studies. International Journal of Radiation Oncology∙Biology∙Physics, 20, 667-676. https://doi.org/10.1016/0360-3016(91)90007-q
[42]
Coia, L., Won, M., Lanciano, R., Marcial, V.A., Martz, K. and Hanks, G. (1990) The Patterns of Care Outcome Study for Cancer of the Uterine Cervix Results of the Second National Practice Survey. Cancer, 66, 2451-2456. https://doi.org/10.1002/1097-0142(19901215)66:12<2451::aid-cncr2820661202>3.0.co;2-5
[43]
Dossou, S., James, L., Bakkali, H., Afif, M., Rahali, L., Irigo, J., et al. (2015) Les facteurs pronostiques de survie sans récidive chez les patientes atteintes de tumeur du col de l’utérus. Pan African Medical Journal, 21, Article 305. https://doi.org/10.11604/pamj.2015.21.305.5427
[44]
Annede, P., Gouy, S., Haie-Meder, C., Morice, P. and Chargari, C. (2019) Places respectives de la radiothérapie et de la chirurgie dans les cancers du col utérin. Cancer/Radiothérapie, 23, 737-744. https://doi.org/10.1016/j.canrad.2019.07.151
[45]
Delgado, G., Bundy, B., Zaino, R., Sevin, B., Creasman, W.T. and Major, F. (1990) Prospective Surgical-Pathological Study of Disease-Free Interval in Patients with Stage IB Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study. Gynecologic Oncology, 38, 352-357. https://doi.org/10.1016/0090-8258(90)90072-s
[46]
Coibion, C. and Thille, A. (2016) Cancer du col utérin dans les pays industrialisés et ailleurs: Quel bilan d’extension selon les moyens? Imagerie de la Femme, 26, 86-94. https://doi.org/10.1016/j.femme.2016.03.003
[47]
Pecorelli, S., Zigliani, L. and Odicino, F. (2009) Revised FIGO Staging for Carcinoma of the Cervix. International Journal of Gynecology & Obstetrics, 105, 107-108. https://doi.org/10.1016/j.ijgo.2009.02.009
[48]
Bannour, N., Boughizane, S., Naifer, R., Slama, O., Trabelsi, A., Bibi, M., et al. (2004) Le cancer invasif du col utérin dans le centre tunisien. Approches épidémiologique, clinique et thérapeutique. Étude rétrospective de 96 cas. ONCOLOGIE, 6, 481-488. https://doi.org/10.1007/s10269-004-0117-5
[49]
Hong, J., Tsai, C., Chang, J.T., Wang, C., Lai, C., Lee, S.P., et al. (1998) The Prognostic Significance of Pre-and Posttreatment SCC Levels in Patients with Squamous Cell Carcinoma of the Cervix Treated by Radiotherapy. International Journal of Radiation Oncology∙Biology∙Physics, 41, 823-830. https://doi.org/10.1016/s0360-3016(98)00147-3
[50]
Newman, H., Jur, B., Tames, K.W. and Smith, C.W. (1983) Treatment of Cancer of the Cervix with a High-Dose-Rate Afterloading Machine (The Cathetron). International Journal of Radiation Oncology∙Biology∙Physics, 9, 931-937. https://doi.org/10.1016/0360-3016(83)90021-4
[51]
Song, S., Rudra, S., Hasselle, M.D., Dorn, P.L., Mell, L.K., Mundt, A.J., et al. (2012) The Effect of Treatment Time in Locally Advanced Cervical Cancer in the Era of Concurrent Chemoradiotherapy. Cancer, 119, 325-331. https://doi.org/10.1002/cncr.27652
[52]
Petereit, D.G., Sarkaria, J.N., Chappell, R., Fowler, J.F., Hartmann, T.J., Kinsella, T.J., et al. (1995) The Adverse Effect of Treatment Prolongation in Cervical Carcinoma. International Journal of Radiation Oncology∙Biology∙Physics, 32, 1301-1307. https://doi.org/10.1016/0360-3016(94)00635-x
[53]
Fyles, A., Keane, T.J., Barton, M. and Simm, J. (1992) The Effect of Treatment Duration in the Local Control of Cervix Cancer. Radiotherapy and Oncology, 25, 273-279. https://doi.org/10.1016/0167-8140(92)90247-r
[54]
Girinsky, T., Rey, A., Roche, B., Haie, C., Gerbaulet, A., Randrianarivello, H., et al. (1993) Overall Treatment Time in Advanced Cervical Carcinomas: A Critical Parameter in Treatment Outcome. International Journal of Radiation Oncology∙Biology∙Physics, 27, 1051-1056. https://doi.org/10.1016/0360-3016(93)90522-w
[55]
Perez, C.A., Grigsby, P.W., Castro-Vita, H. and Lockett, M.A. (1995) Carcinoma of the Uterine Cervix. I. Impact of Prolongation of Overall Treatment Time and Timing of Brachytherapy on Outcome of Radiation Therapy. International Journal of Radiation Oncology∙Biology∙Physics, 32, 1275-1288. https://doi.org/10.1016/0360-3016(95)00220-s
[56]
Green, J.A., Kirwan, J.M., Tierney, J.F., Symonds, P., Fresco, L., Collingwood, M., et al. (2001) Survival and Recurrence after Concomitant Chemotherapy and Radiotherapy for Cancer of the Uterine Cervix: A Systematic Review and Meta-Analysis. The Lancet, 358, 781-786. https://doi.org/10.1016/s0140-6736(01)05965-7
[57]
Kokka, F., Bryant, A., Olaitan, A., Brockbank, E., Powell, M. and Oram, D. (2022) Hysterectomy with Radiotherapy or Chemotherapy or Both for Women with Locally Advanced Cervical Cancer. Cochrane Database of Systematic Reviews, No. 8, CD010260. https://doi.org/10.1002/14651858.cd010260.pub3
[58]
Traoré, B., Dem, A., Kasse, A.A., Dieng, M.M., Gaye, M., Diop, M., et al. (2012) Résécabilité des cancers localement avancés du col utérin après radiothérapie externe néoadjuvante. Journal Africain du Cancer/African Journal of Cancer, 4, 209-214. https://doi.org/10.1007/s12558-012-0224-y