BACKGROUND: Models predicting recurrence risk (RR) of cervical cancer are used to tailor adjuvant treatment after radical surgery. The goal of our study was to compare available prognostic factors and to develop a prognostic model that would be easy to standardise and use in routine clinical practice. METHODS: All consecutive patients with early-stage cervical cancer treated by primary surgery in a single referral centre (01/2007-12/2016) were eligible if assessed by standardised protocols for pre-operative imaging and pathology. Fifteen prognostic markers were evaluated in 379 patients, out of which 320 lymph node (LN)-negative. RESULTS: The best predictive model for the whole cohort entailed a combination of tumour-free distance (TFD) ≤ 3.5 mm and LN positivity, which separated two subgroups with a substantially distinct RR 36% and 6.5%, respectively. In LN-negative patients, a combination of TFD ≤ 3.5 mm and adenosquamous tumour type separated a group of nine patients with RR 33% from the rest of the group with 6% RR. CONCLUSIONS: A newly identified prognostic marker, TFD, surpassed all traditional tumour-related markers in the RR assessment. Predictive models combining TFD, which can be easily accessed on pre-operative imaging, with LN status or tumour type can be used in daily practice and can help to identify patients with the highest RR.

Department of Pathology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Studnickova 2 Prague 2 12800 Czech Republic

Department of Radiology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague U Nemocnice 499 2 Prague 2 12808 Czech Republic

Gynecologic Oncology Center Department of Obstetrics and Gynecology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Apolinarska 18 Prague 2 12800 Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Kamenice 126 3 Brno 62500 Czech Republic

Institute of Health Information and Statistics of the Czech Republic Palackeho Namesti 4 P O Box 60 Prague 2 12801 Czech Republic

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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. Radiother. Oncol. 2018;127:404–416. doi: 10.1016/j.radonc.2018.03.003. PubMed DOI

Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, et al. Cervical cancer, version 3.2019, NCCN clinical practice guidelines in oncology. J. Natl Compr. Canc Netw. 2019;17:64–84. doi: 10.6004/jnccn.2019.0001. PubMed DOI

Delgado G, Bundy B, Zaino R, Sevin B-U, Creasman WT, Major F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol. Oncol. 1990;38:352–357. doi: 10.1016/0090-8258(90)90072-S. PubMed DOI

Alvarez RD, Soong SJ, Kinney WK, Reid GC, Schray MF, Podratz KC, et al. Identification of prognostic factors and risk groups in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix. Gynecol. Oncol. 1989;35:130–135. doi: 10.1016/0090-8258(89)90029-2. PubMed DOI

Ho CM, Chien TY, Huang SH, Wu CJ, Shih BY, Chang SC. Multivariate analysis of the prognostic factors and outcomes in early cervical cancer patients undergoing radical hysterectomy. Gynecol. Oncol. 2014;93:458–464. doi: 10.1016/j.ygyno.2004.01.026. PubMed DOI

Kamura T, Tsukamoto N, Tsuruchi N, Saito T, Matsuyama T, Akazawa K, et al. Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy. Cancer. 1992;69:181–186. doi: 10.1002/1097-0142(19920101)69:1<181::AID-CNCR2820690130>3.0.CO;2-B. PubMed DOI

Lai CH, Chang CJ, Huang HJ, Hsueh S, Chao A, Yang JE, et al. Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery. J. Clin. Oncol. 2007;25:3628–3634. doi: 10.1200/JCO.2007.11.2995. PubMed DOI

Sevin BU, Lu Y, Bloch DA, Nadji M, Koechli OR, Averette HE. Surgically defined prognostic parameters in patients with early cervical carcinoma. A multivariate survival tree analysis. Cancer. 1996;78:1438–1446. doi: 10.1002/(SICI)1097-0142(19961001)78:7<1438::AID-CNCR10>3.0.CO;2-0. PubMed DOI

Yuan CC, Wang PH, Lai CR, Yen MS, Chen CY, Juang CM. Prognosis-predicting system based on factors related to survival of cervical carcinoma. Int. J. Gynaecol. Obstet. 1998;63:163–167. doi: 10.1016/S0020-7292(98)00142-8. PubMed DOI

Kristensen GB, Abeler VM, Risberg B, Trop C, Bryne M. Tumor size, depth of invasion, and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma. Gynecol. Oncol. 1999;74:245–251. doi: 10.1006/gyno.1999.5420. PubMed DOI

Grisaru DA, Covens A, Franssen E, Chapman W, Shaw P, Colgan T, et al. Histopathologic score predicts recurrence free survival after radical surgery in patients with stage IA2-IB1-2 cervical carcinoma. Cancer. 2003;97:1904–1908. doi: 10.1002/cncr.11269. PubMed DOI

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;73:177–183. doi: 10.1006/gyno.1999.5387. PubMed DOI

Van de Putte G, Lie AK, Vach W, Baekelandt M, Kristensen GB. Risk grouping in stage IB squamous cell cervical carcinoma. Gynecol. Oncol. 2005;99:106–112. doi: 10.1016/j.ygyno.2005.05.026. PubMed DOI

Sartori E, Tisi G, Chiudinelli F, La Face B, Franzini R, Pecorelli S. Early stage cervical cancer: adjuvant treatment in negative lymph node cases. Gynecol. Oncol. 2007;107:170–174. doi: 10.1016/j.ygyno.2007.07.026. PubMed DOI

Chen Y, Zhang L, Tian J, Fu X, Ren X, Hao Q. Significance of the absolute number and ratio of metastatic lymph nodes in predicting postoperative survival for the International Federation of Gynecology and Obstetrics stage IA2 to IIA cervical cancer. Int. J. Gynecol. Cancer. 2003;23:157–163. doi: 10.1097/IGC.0b013e3182778bcf. PubMed DOI

Lee YJ, Kim DY, Lee SW, Park JY, Suh DS, Kim JH, et al. A postoperative scoring system for distant recurrence in node-positive cervical cancer patients after radical hysterectomy and pelvic lymph node dissection with para-aortic lymph node sampling or dissection. Gynecol. Oncol. 2007;144:536–540. doi: 10.1016/j.ygyno.2017.01.001. PubMed DOI

Wang C, Yang C, Wang W, Xia B, Li K, Sun F, et al. A prognostic nomogram for cervical cancer after surgery from SEER database. J. Cancer. 2018;9:3923–3928. doi: 10.7150/jca.26220. PubMed DOI PMC

Derks M, van der Velden J, de Kroon CD, Nijman HW, van Lonkhuijzen L, van der Zee AGJ, et al. Surgical treatment of early-stage cervical cancer: a multi-institution experience in 2124 cases in The Netherlands over a 30-year period. Int. J. Gynecol. Cancer. 2018;28:757–763. doi: 10.1097/IGC.0000000000001228. PubMed DOI

Biewenga P, van der Velden J, Mol BW, Stalpers LJ, Schilthuis MS, van der Steeg JW, et al. Validation of existing prognostic models in patients with early-stage cervical cancer. Gynecol. Oncol. 2009;115:277–284. doi: 10.1016/j.ygyno.2009.08.006. PubMed DOI

Cibula D, Abu-Rustum NR. Pelvic lymphadenectomy in cervical cancer-surgical anatomy and proposal for a new classification system. Gynecol. Oncol. 2010;116:33–37. doi: 10.1016/j.ygyno.2009.09.003. PubMed DOI

Querleu D, Cibula D, Abu-Rustum NR. 2017 update on the Querleu-Morrow classification of radical hysterectomy. Ann. Surg. Oncol. 2017;24:3406–3412. doi: 10.1245/s10434-017-6031-z. PubMed DOI PMC

Testa AC, Ludovisi M, Manfredi R, Zannoni G, Gui B, Basso D, et al. Transvaginal ultrasonography and magnetic resonance imaging for assessment of presence, size and extent of invasive cervical cancer. Ultrasound Obstet. Gynecol. 2009;34:335–344. doi: 10.1002/uog.7325. PubMed DOI

Fischerova D, Cibula D, Stenhova H, Vondrichova H, Calda P, Zikan M, et al. Transrectal ultrasound and magnetic resonance imaging in staging of early cervical cancer. Int. J. Gynecol. Cancer. 2008;18:766–772. doi: 10.1111/j.1525-1438.2007.01072.x. PubMed DOI

Epstein E, Testa A, Gaurilcikas A, Di Legge A, Ameye L, Atstupenaite V, et al. Early-stage cervical cancer: tumor delineation by magnetic resonance imaging and ultrasound—a European multicenter trial. Gynecol. Oncol. 2013;128:449–453. doi: 10.1016/j.ygyno.2012.09.025. PubMed DOI

Chiappa V, Di Legge A, Valentini AL, Gui B, Micco M, Ludovisi M, et al. Agreement of two-dimensional and three-dimensional transvaginal ultrasound with magnetic resonance imaging in assessment of parametrial infiltration in cervical cancer. Ultrasound Obstet. Gynecol. 2015;45:459–469. doi: 10.1002/uog.14637. PubMed DOI

Education and Practical Standards Committee, European Federation of Societies for Ultrasound in Medicine and Biology. Minimum training recommendations for the practice of medical ultrasound. Ultraschall Med.27, 79–105 (2006). PubMed

Fischerova D. Ultrasound scanning of the pelvis and abdomen for staging of gynecological tumors: a review. Ultrasound Obstet. Gynecol. 2011;38:246–266. doi: 10.1002/uog.10054. PubMed DOI

Cibula D, McCluggage WG. Sentinel lymph node (SLN) concept in cervical cancer: Current limitations and unanswered questions. Gynecol. Oncol. 2019;152:202–207. doi: 10.1016/j.ygyno.2018.10.007. PubMed DOI

Tsukamoto T. The studies on the spreading modus of the uterine cervical cancer: especially a new proposal of the postoperative histological classification. Shinshu Med J. 1966;15:354–383.

Noguchi H, Shiozawa K, Tsukamoto T, Tsukahara Y, Iwai S, Fukuta T. The postoperative classification for uterine cervical cancer and its clinical evaluation. Gynecol. Oncol. 1983;16:219–231. doi: 10.1016/0090-8258(83)90096-3. PubMed DOI

Kishi Y, Hashimoto Y, Sakamoto Y, Inui S. Thickness of uninvolved fibromuscular stroma and extrauterine spread of carcinoma of the uterine cervix. Cancer. 1987;60:2331–2336. doi: 10.1002/1097-0142(19871101)60:9<2331::AID-CNCR2820600936>3.0.CO;2-O. PubMed DOI

Landoni F, Bocciolone L, Perego P, Maneo A, Bratina G, Mangioni C. Cancer of the cervix, FIGO stages IB and IIA: patterns of local growth and paracervical extension. Int. J. Gynecol. Cancer. 1995;5:329–334. doi: 10.1046/j.1525-1438.1995.05050329.x. PubMed DOI

The Role of Imaging in Cervical Cancer Staging: ESGO/ESTRO/ESP Guidelines (Update 2023)

The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer