Fertility-sparing surgical interventions for low-risk, non-metastatic gestational trophoblastic neoplasia

The primary treatment approach for addressing low-risk nonmetastatic gestational trophoblastic neoplasia (LR-NMGTN) in women desiring fertility preservation involves chemotherapy. An alternative option for treatment is fertility-sparing surgical interventions, either alone or in combination with adjuvant chemotherapy. The hypothesised advantages of choosing fertility-sparing surgery in cases of LR-NMGTN include potential avoidance of adverse effects associated with chemotherapy, potential reduction in the number of chemotherapy cycles required to achieve complete remission, and potential reduction in time to remission.

To measure the benefits and harms of fertility-sparing surgical interventions, with or without adjuvant chemotherapy, compared to primary chemotherapy alone, for the treatment of women with low-risk, non-metastatic gestational trophoblastic neoplasia (LR-NMGTN).

We searched CENTRAL, MEDLINE, Embase, Web of Science, ClinicalTrials.gov and WHO ICTRP on 31 January 2024. We also searched abstracts of scientific meetings and reference lists of included studies.

We included all randomised controlled trials (RCTs) comparing fertility-sparing surgical interventions, with or without subsequent adjuvant chemotherapy, versus primary chemotherapy as standard care for the treatment of women with LR-NMGTN.

We employed standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of evidence for each outcome, if available. We focused on the following outcomes: treatment success rate, relapse, disease-specific mortality, death due to treatment, pregnancy rate, quality of life, and any adverse events.

We included two RCTs, with a total of 151 participants contributing data to our analyses. Both studies used uterine curettage as the fertility-sparing surgical intervention. Fertility-sparing surgical intervention without subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 62 participants with varying hCG (human chorionic gonadotrophin) levels evaluated this comparison. Most of our outcomes of interest were not measured in this study. The relative risk of experiencing any adverse event could not be estimated as chemotherapy adverse effects were not reported. The study reported that there were no surgical complications. Chemotherapy was administered to 50% of participants in the intervention group after curettage because their hCG levels increased. Fertility-sparing surgical intervention with subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 89 participants with hCG levels < 5000 IU/L evaluated this comparison. We judged the risk of bias in the study to be high. The evidence was very uncertain about the effect of uterine curettage with subsequent adjuvant chemotherapy on treatment success rate (RR 1.03, 95% CI 0.86 to1.23; 86 participants), relapse (RR 0.5, 95% CI 0.05 to 5.31; 86 participants), pregnancy rate (RR 0.86, 95% CI 0.31 to 2.34; 86 participants), and rate of adverse events (RR 1.15, 95% CI 0.63 to 2.13; 86 participants), all very low certainty evidence. The relative risks of disease-specific mortality and death due to treatment could not be estimated as there were no deaths in either group. There were no results for quality of life as this outcome was not reported.

Uterine curettage is the only fertility-sparing surgical intervention for LR-NMGTN that has been evaluated in a randomised controlled trial. The evidence is very uncertain about the benefits and harms of uterine curettage, with or without subsequent adjuvant chemotherapy, compared to primary chemotherapy alone. The two available studies are small with a high risk of bias, and future research may find substantially different results for all reported outcomes. Larger RCTs, with appropriate clinical outcome measures, would be required to determine the benefits or harms of fertility-sparing surgical interventions for this population.