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Recurrence and resistance risk factors in low-risk gestational trophoblastic neoplasia
  1. Mariza Branco-Silva1,
  2. Izildinha Maestá2,
  3. Neil Horowitz3,4,
  4. Kevin Elias3,4,
  5. Michael Seckl5 and
  6. Ross Berkowitz3,4
    1. 1Postgraduate Program in Tocogynecology, Botucatu Medical School, Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Medicina - Câmpus de Botucatu, Botucatu, Brazil
    2. 2Botucatu Trophoblastic Disease Center, Botucatu Medical School Hospital, Department of Gynecology and Obstetrics, Sao Paulo State University Julio de Mesquita Filho, Botucatu, Brazil
    3. 3New England Trophoblastic Disease Center, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    4. 4Division of Gynecologic Oncology,Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA
    5. 5Trophoblastic Tumour Screening and Treatment Centre, Imperial College London - Charing Cross Campus, London, UK
    1. Correspondence to Dr Mariza Branco-Silva; branco.silva{at}unesp.br

    Abstract

    Gestational trophoblastic neoplasia (GTN) is a group of rare but highly curable pregnancy‐related tumors, especially in low-risk cases. However, around 25% of patients with GTN develop either resistant or recurrent disease after initial chemotherapy. To enhance the understanding of the mechanisms driving treatment failures and to develop more personalized and effective therapeutic strategies, this review explored diverse factors influencing low-risk GTN prognosis. These factors include FIGO (International Federation of Gynecology and Obstetrics) risk score, histology, patient age, pregnancy type, human chorionic gonadotropin (hCG) levels, disease duration, tumor characteristics, metastasis, Doppler ultrasonography, and consolidation chemotherapy. Additionally, the review examined independent risk determinants for disease recurrence and resistance to single-agent chemotherapy in patients with low-risk GTN. In most previous studies on the risk factors related to low-risk GTN, resistance and recurrence have typically been examined independently, despite their overlapping and interrelated nature. Furthermore, they often involve small sample sizes, suffer from methodological shortcomings, and exhibit limited statistical power.

    Studies utilizing multivariate analysis have shown that independent risk determinants for resistance to first-line treatment include FIGO score, metastatic disease, pre-treatment hCG level, interval between antecedent pregnancy and GTN diagnosis, tumor size, uterine artery pulsatility index (UAPI), choriocarcinoma, lung metastases, lung nodule size, and clearance hCG quartile. The independent predictive factors associated with recurrence include lung metastases, lung nodule size, interval between antecedent pregnancy and chemotherapy, interval from first chemotherapy to hCG normalization, post-delivery low-risk GTN, number of chemotherapy courses to achieve hCG normalization, and number of consolidation chemotherapy cycles. However, while these identified predictive factors offer valuable guidance, the variability in definitions and populations across studies may have implications for the generalizability of their findings. A comprehensive approach using clear definitions and taking into account multiple predictive factors may be necessary for accurately assessing the risk of resistance and recurrence in patients with low-risk GTN.

    • Gestational Trophoblastic Disease
    • Trophoblastic Neoplasms

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    Footnotes

    • MS and RB are joint senior authors.

    • X @kevin_elias

    • Contributors Study concept and design, data acquisition: MBS (guarantor). Data interpretation, drafting of the manuscript, revision of the manuscript, and approval of final version: all authors.

    • Funding This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Finance Code 001 (Branco-Silva, M: Process: CAPES-PRINT – 88887. 936593/2024-0 and CAPES-PROEX 88887.824444/2023-00; Maesta, I: Process: CAPES-PRINT - 88887.936692/2024-00). The funding agencies had no direct role in the generation of the data or the manuscript.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.