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Not all stage I and II endometrial cancers are created equal: Recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy alone in all subgroups of early-stage high-intermediate and high-risk endometrial cancer

Published:October 14, 2022DOI:https://doi.org/10.1016/j.ygyno.2022.10.004

      Highlights

      • Some subgroups of high-intermediate-risk and high-risk endometrial cancer (EC) represent <1% of all ECs.
      • Three-year cause-specific survival after observation or brachytherapy only is higher than 85% in 15 of the 16 subgroups.
      • Observation or brachytherapy may be adequate in stage I endometrioid ECs without grade 3 or lymphovascular space invasion.
      • Non-endometrioid ECs without myometrial invasion have a good prognosis with only observation or vaginal brachytherapy.

      Abstract

      Objective

      To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC).

      Methods

      We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors.

      Results

      Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology.

      Conclusions

      Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

      Keywords

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      References

        • Siegel R.L.
        • Miller K.D.
        • Fuchs H.E.
        • Jemal A.
        Cancer statistics, 2021.
        CA Cancer J. Clin. 2021; 71: 7-33
        • NCCN
        NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) - Uterine Neoplasms Version 1.
        2022: 2022
        • Colombo N.
        • Creutzberg C.
        • Amant F.
        • Bosse T.
        • Gonzalez-Martin A.
        • Ledermann J.
        • et al.
        ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up.
        Int. J. Gynecol. Cancer. 2016; 26: 2-30
        • Concin N.
        • Matias-Guiu X.
        • Vergote I.
        • Cibula D.
        • Mirza M.R.
        • Marnitz S.
        • et al.
        ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma.
        Int. J. Gynecol. Cancer. 2021; 31: 12-39
        • Morrow C.P.
        • Bundy B.N.
        • Kurman R.J.
        • Creasman W.T.
        • Heller P.
        • Homesley H.D.
        • et al.
        Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a gynecologic oncology group study.
        Gynecol. Oncol. 1991; 40: 55-65
        • Maggino T.
        • Romagnolo C.
        • Landoni F.
        • Sartori E.
        • Zola P.
        • Gadducci A.
        An analysis of approaches to the management of endometrial cancer in North America: a CTF study.
        Gynecol. Oncol. 1998; 68: 274-279
        • Creutzberg C.L.
        • van Putten W.L.
        • Koper P.C.
        • Lybeert M.L.
        • Jobsen J.J.
        • Warlam-Rodenhuis C.C.
        • et al.
        Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post operative radiation therapy in endometrial carcinoma.
        Lancet. 2000; 355: 1404-1411
        • Keys H.M.
        • Roberts J.A.
        • Brunetto V.L.
        • Zaino R.J.
        • Spirtos N.M.
        • Bloss J.D.
        • et al.
        A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.
        Gynecol. Oncol. 2004; 92: 744-751
        • Eifel P.J.
        High intermediate risk endometrial cancer. What is it?.
        Int. J. Gynecol. Cancer. 2019; 29: 1084-1085
        • Nout R.A.
        • Smit V.T.
        • Putter H.
        • Jurgenliemk-Schulz I.M.
        • Jobsen J.J.
        • Lutgens L.C.
        • et al.
        Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
        Lancet. 2010; 375: 816-823
        • Creutzberg C.L.
        • van Putten W.L.
        • Warlam-Rodenhuis C.C.
        • van den Bergh A.C.
        • de Winter K.A.
        • Koper P.C.
        • et al.
        Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the postoperative radiation therapy in endometrial carcinoma trial.
        J. Clin. Oncol. 2004; 22: 1234-1241
        • Randall M.E.
        • Filiaci V.
        • McMeekin D.S.
        • von Gruenigen V.
        • Huang H.
        • Yashar C.M.
        • et al.
        Phase III trial: adjuvant pelvic radiation therapy versus vaginal brachytherapy plus paclitaxel/carboplatin in high-intermediate and high-risk early stage endometrial Cancer.
        J. Clin. Oncol. 2019; 37: 1810-1818
        • de Boer S.M.
        • Powell M.E.
        • Mileshkin L.
        • Katsaros D.
        • Bessette P.
        • Haie-Meder C.
        • et al.
        Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial.
        Lancet Oncol. 2019; 20: 1273-1285
        • Randall M.
        Management of high-risk endometrial cancer: are we there yet?.
        Lancet Oncol. 2019; 20: 1192-1193
        • Li R.
        • Shinde A.
        • Han E.
        • Lee S.
        • Beriwal S.
        • Harkenrider M.
        • et al.
        A proposal for a new classification of “unfavorable risk criteria” in patients with stage I endometrial cancer.
        Int. J. Gynecol. Cancer. 2019; 29: 1086-1093
        • Bendifallah S.
        • Canlorbe G.
        • Collinet P.
        • Arsene E.
        • Huguet F.
        • Coutant C.
        • et al.
        Just how accurate are the major risk stratification systems for early-stage endometrial cancer?.
        Br. J. Cancer. 2015; 112: 793-801
        • Pecorelli S.
        Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium.
        Int. J. Gynaecol. Obstet. 2009; 105: 103-104
        • Maggi R.
        • Lissoni A.
        • Spina F.
        • Melpignano M.
        • Zola P.
        • Favalli G.
        • et al.
        Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial.
        Br. J. Cancer. 2006; 95: 266-271
        • Susumu N.
        • Sagae S.
        • Udagawa Y.
        • Niwa K.
        • Kuramoto H.
        • Satoh S.
        • et al.
        Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study.
        Gynecol. Oncol. 2008; 108: 226-233
        • Hogberg T.
        • Signorelli M.
        • de Oliveira C.F.
        • Fossati R.
        • Lissoni A.A.
        • Sorbe B.
        • et al.
        Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies.
        Eur. J. Cancer. 2010; 46: 2422-2431
        • Kuoppala T.
        • Maenpaa J.
        • Tomas E.
        • Puistola U.
        • Salmi T.
        • Grenman S.
        • et al.
        Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy.
        Gynecol. Oncol. 2008; 110: 190-195
        • Matei D.
        • Filiaci V.
        • Randall M.E.
        • Mutch D.
        • Steinhoff M.M.
        • DiSilvestro P.A.
        • et al.
        Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer.
        N. Engl. J. Med. 2019; 380: 2317-2326
        • Johnson N.
        • Bryant A.
        • Miles T.
        • Hogberg T.
        • Cornes P.
        Adjuvant chemotherapy for endometrial cancer after hysterectomy.
        Cochrane Database Syst. Rev. 2011; : CD003175
        • de Boer S.M.
        • Powell M.E.
        • Mileshkin L.
        • Katsaros D.
        • Bessette P.
        • Haie-Meder C.
        • et al.
        Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial.
        Lancet Oncol. 2018; 19: 295-309
        • Randall M.
        Management of high-risk endometrial cancer: are we there yet?.
        Lancet Oncol. 2019; 20: 1192-1193
        • ANZGOG
        • Blinman P.
        • Mileshkin L.
        • Khaw P.
        • Goss G.
        • Johnson C.
        • et al.
        Patients’ and clinicians’ preferences for adjuvant chemotherapy in endometrial cancer: an ANZGOG substudy of the PORTEC-3 intergroup randomised trial.
        Br. J. Cancer. 2016; 115: 1179-1185
        • León-Castillo A.
        • de Boer S.M.
        • Powell M.E.
        • Mileshkin L.R.
        • Mackay H.J.
        • Leary A.
        • et al.
        Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy.
        J. Clin. Oncol. 2020; 38: 3388-3397
        • Talhouk A.
        • McConechy M.K.
        • Leung S.
        • Yang W.
        • Lum A.
        • Senz J.
        • et al.
        Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer.
        Cancer. 2017; 123: 802-813
        • Kommoss S.
        • McConechy M.K.
        • Kommoss F.
        • Leung S.
        • Bunz A.
        • Magrill J.
        • et al.
        Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series.
        Ann. Oncol. 2018; 29: 1180-1188