Reviewing prognostic factors associated with recurrence in clinically early-stage low-risk endometrial cancer

ABSTRACT

Objective: We sought to re-explore the association between well-known prognostic factors and recurrence in presumed early-stage low-risk endometrial cancer (EC).

Methods: A retrospective cohort study was carried out on patients who underwent surgical treatment by the same surgeon for presumed early-stage low-risk EC between September 2003 to August 2017. The prognostic value of well-known clinicopathological factors for diseasefree survival (DFS) was reviewed by univariate log-rank test.

Results: One hundred and five patients fit the criteria for this analysis. These patients underwent total hysterectomy plus bilateral salpingo-oophorectomy with no lymph nodes dissection (10.5%) or with a sampling dissection alone (89.5%). Adjuvant therapies were applied in 52 (40.1%) of them as pelvic radiotherapy (29.5%) or chemoradiation (11.4%). Our cumulative 3y-DFS and OS were 88.1% and 97.7%, respectively. The univariate survival analysis confirmed histological grade 3 (3y-DFS of 89.9% vs. 33.3%, p=0.004), MMI ≥50% (3y-DFS of 95.2% vs. 71.3%, p=0.003), lymph node metastasis (3y-DFS of 88.3% vs. 60%; p=0.028) and more advanced pathological stages (3y-DFS of 91.2% vs. 56.3; p<0.001) as significantly associated to recurrences.

Conclusion: We confirmed the association of classical prognostic factors such as high histological grade, deeper MMI, lymph node metastasis and more advanced pathological stages with disease recurrence in this cohort of patients from Northeast Brazil. Further efforts are needed to avoid overtreatment in patients with low risk of relapses.

RESUMO

Objetivo: Reexplorar a associação entre fatores prognósticos bem conhecidos e recorrência em pacientes com câncer de endométrico (EC) de baixo risco em em estágio presumivelmente inicial.

Métodos: Foi realizado um estudo de coorte retrospectivo em pacientes submetidos a tratamento cirúrgico pelo mesmo cirurgião para EC de baixo risco em estágio inicial entre setembro de 2003 a agosto de 2017. O valor prognóstico de fatores clínico-patológicos conhecidos para sobrevida livre de doença (DFS) foi revisado pelo teste log-rank univariado.

Resultados: Cento e cinco pacientes preencheram os critérios para esta análise. Essas pacientes foram submetidas à histerectomia total mais salpingo-ooforectomia bilateral sem dissecção de linfonodos (10,5%) ou apenas com dissecção por amostragem (89,5%). Terapias adjuvantes foram aplicadas em 52 (40,1%) deles como radioterapia pélvica (29,5%) ou quimiorradiação (11,4%). As taxas de 3y-DFS e OS foram de 88,1% e 97,7%, respectivamente. A análise de sobrevida univariada confirmou grau histológico 3 (3y-DFS de 89,9% vs. 33,3%, p=0,004), MMI ≥50% (3y-DFS de 95,2% vs. 71,3%, p=0,003), metástase linfonodal (3a-DFS de 88,3% vs. 60%; p=0,028) e estádios patológicos mais avançados (3a-DFS de 91,2% vs. 56,3; p<0,001) como significativamente associados às recidivas.

Conclusão: Confirmamos a associação de fatores prognósticos clássicos como alto grau histológico, MMI profunda, metástase linfonodal e estágios patológicos mais avançados com recorrência da doença nesta coorte de pacientes do Nordeste do Brasil. Mais esforços são necessários para evitar o tratamento excessivo em pacientes com baixo risco de recaídas.

Keywords:

Endometrial neoplasm - Prognosis - Survival analysis - Disease-free survival - Locoregional neoplasm recurrences

Descritores:

Neoplasia endometrial - Prognóstico - Análise de sobrevivência - Sobrevida livre de doença - Recorrências de neoplasias locorregionais

Contribution to authorship:

Study concept and design: Batista TP; Acquisition of data: Bezerra ALR, Santana RP, Guimarães-Augusto CM, Morais NS and Ventura MLAB; Analysis and interpretation of data: All authors, mainly Batista TP and Bezerra ALR; Drafting of the manuscript: Batista TP; Critical revision of the manuscript for important intellectual content: All authors, mainly Bezerra ALR; Administrative and material support: Bezerra ALR; Study supervision: Bezerra ALR.

Publikationsverlauf

Eingereicht: 01. Februar 2021

Angenommen: 26. Oktober 2021

Artikel online veröffentlicht:
18. Februar 2022

• REFERENCES

• 1 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (06) 394-424 https://doi.org/10.3322/caac.21492
• 2 Bezerra AL, Batista TP, Martins MR, Carneiro VC. Surgical treatment of clinically early-stage endometrial carcinoma without systematic lymphadenectomy. Rev Assoc Med Bras 2014; Nov/Dec; 60 (06) 571-576 https://doi.org/10.1590/1806-9282.60.06.017
• 3 Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD. 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; Mar; 92 (03) 744-751 https://doi.org/10.1016/j.ygyno.2003.11.048
• 4 Colombo N, Creutzberg C, Amant F, Bosse T, GonzálezMartín A, Ledermann J. et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Int J Gynecol Cancer 2016; Jan; 26 (01) 2-30 https://doi.org/10.1097/IGC.0000000000000609
• 5 Jang JW, Lee LJ. External beam, brachytherapy, or chemotherapy? Defining adjuvant therapy for early-stage and high- and high-intermediate-risk endometrial cancer. J Clin Oncol 2019; Jul; 37 (21) 1778-1784 https://doi.org/10.1200/JCO.19.00362
• 6 Talhouk A, McAlpine JN. New classification of endometrial cancers: the development and potential applications of genomic-based classification in research and clinical care. Gynecol Oncol Res Pract 2016; Dec; 3: 14 https://doi.org/10.1186/s40661-016-0035-4
• 7 Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J. et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 2017; Mar; 123 (05) 802-813 https://doi.org/10.1002/cncr.30496
• 8 Kommoss S, McConechy MK, 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; May; 29 (05) 1180-1188 https://doi.org/10.1093/annonc/mdy058
• 9 Travaglino A, Raffone A, Stradella C, Esposito R, Moretta P, Gallo C. et al. Impact of endometrial carcinoma histotype on the prognostic value of the TCGA molecular subgroups. Arch Gynecol Obstet 2020; Apr; 31: 1355-1363 https://doi.org/10.1007/s00404-020-05542-1
• 10 Morrow CP, Bundy BN, Kurman RJ, Creasman WT, Heller P, Homesley HD. 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; Jan; 40 (01) 55-65 https://doi.org/10.1016/0090-8258(91)90086-k
• 11 Panici PB, Basile S, Salerno MG, Di Donato V, Marchetti C, Perniola G. et al. Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma. Am J Obstet Gynecol 2014; Apr; 210 (04) 363.e1-363.e10 https://doi.org/10.1016/j.ajog.2013.12.025
• 12 Anton C, Kleine RT, Mayerhoff E, Diz MPE, Freitas D, Carvalho HA. et al. Ten years of experience with endometrial cancer treatment in a single Brazilian institution: Patient characteristics and outcomes. PLoS One 2020; Mar; 15 (03) e0229543 https://doi.org/10.1371/journal.pone.0229543
• 13 Conlon N, Paula AC, Ashley CW, Sheila S, Brout L, Edaise S. et al. Endometrial carcinomas with a “serous” component in young women are enriched for DNA mismatch repair deficiency, lynch syndrome, and POLE exonuclease domain mutations. Am J Surg Pathol 2020; May; 44 (05) 641-648 https://doi.org/10.1097/PAS.0000000000001461
• 14 Porzio R, Cordini C, Rodolfi AM, Brigati F, Ubiali A, Prietto M. et al. Triple negative endometrial cancer: Incidence and prognosis in a monoinstitutional series of 220 patients. Oncol Lett 2020; Mar; 19 (03) 2522-2526 https://doi.org/10.3892/ol.2020.11329
• 15 Beinse G, Rance B, Just PA, Izac B, Letourneur F, Saidu NEB. et al. Identification of TP53 mutated group using a molecular and immunohistochemical classification of endometrial carcinoma to improve prognostic evaluation for adjuvant treatments. Int J Gynecol Cancer 2020; Mar; 30 (05) 640-647 https://doi.org/10.1136/ijgc-2019-000871
• 16 Liu J, Feng MI, Li S, Nie S, Wang H, Wu S. et al. Identification of molecular markers associated with the progression and prognosis of endometrial cancer: a bioinformatic study. Cancer Cell Int 2020; Feb; 20: 59 https://doi.org/10.1186/s12935-020-1140-3
• 17 Freitas D, Aguiar FN, Anton C, Bacchi CE, Carvalho JP, Carvalho FM. L1 Cell Adhesion Molecule (L1CAM) expression in endometrioid endometrial carcinomas: A possible pre-operative surrogate of lymph vascular space invasion. PLoS One 2018; Dec; 13 (12) e0209294 https://doi.org/10.1371/journal.pone.0209294
• 18 ASTEC Study Group. Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet 2009; Jan; 373 (9658) 125-136 https://doi.org/10.1016/S0140-6736(08)61766-3
• 19 Panici PB, Basile S, Maneschi F, Lissoni AA, Signorelli M, Scambia G. et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst 2008; Dec; 100 (23) 1707-1716 https://doi.org/10.1093/jnci/djn397
• 20 Batista TP, Cavalcanti CL, Tejo AA, Bezerra AL. Accuracy of preoperative endometrial sampling diagnosis for predicting the final pathology grading in uterine endometrioid carcinoma. Eur J Surg Oncol 2016; Sep; 42 (09) 1367-1371 https://doi.org/10.1016/j.ejso.2016.03.009
• 21 Wortman BG, Bosse T, Nout RA, Lutgens LCHW, Van Der Steen-Banasik EM, Westerveld H. et al. Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: evaluation of the pilot phase of the PORTEC-4a trial. Gynecol Oncol 2018; Oct; 151 (01) 6975 https://doi.org/10.1016/j.ygyno.2018.07.020