Gestational trophoblastic neoplasia (GTN) is the only gynecological malignant tumor related to pregnancy that can be cured by chemotherapy. Patients with metastatic disease, FIGO scores of 5-6, or histologic diagnosis of choriocarcinoma are more likely to require second-line therapy than Patients with nonmetastatic disease, FIGO risk scores lower than 4, and patients who do not have choriocarcinoma[1,2]. Several controversies exist within the risk score with one of the current key challenges being whether low-risk patients scoring 5-6 should be still considered low risk and initially treated with single-agent chemotherapy, given that these patients have a higher risk of resistance to single-agent chemotherapy[3]. The rate of resistance to first-line single-agent chemotherapy in low-risk GTN patients with a high FIGO/WHO prognostic score of 5–6 has been shown to be 14 times higher than that in patients with a low FIGO/WHO prognostic score of 0–4 [4]. It is still controversial whether combination chemotherapy regimens work better.
The patients with low-risk GTN who were admitted to the West China Second University Hospital of Sichuan University from 2012 to 2019 were the subjects of the present study. The inclusion criteria was Stage I–III according to the 2000 FIGO GTN anatomical staging, with a FIGO/WHO prognostic score 5-6. The exclusion criteria were: (1)confirmed pathology of placental site trophoblastic tumor (PSTT) , choriocarcinoma or epithelioid trophoblastic tumor (ETT); (2) receipt of non-standard treatment; (3) receipt of germicidal treatment such as MTX or traditional Chinese medicine; and (4) coexistence of other malignant tumors.
Patients were divided into a single-agent chemotherapy group and a combination chemotherapy group according to their regimen at the time of admission. The single-agent regimens include 5-day Methotrexate (MTX) or Actinomycin D, and the combination regimens include Methotrexate (MTX) +Actinomycin D or EMA-CO. The baseline of patients with FIGO/WHO prognostic score（5-6）is shown in table 1.
The efficacy evaluation of single-agent and combination chemotherapy is shown in table 2. A total of 224 low-risk GTN patients were enrolled. The follow-up time was 12–74 months, during which there were 3 (1.34%) cases of recurrence and no deaths. 75 patients (33.5%) had a FIGO/WHO prognostic score of 5–6, among which 46 (85.2%) developed drug resistance. The number of chemotherapy courses was 7.7±1.8, and the number of chemotherapy courses required for β-hCG to return to normal was 5.4±1.8. There were 29 patients who were undergoing single-agent chemotherapy, among which 22 (75.9%) developed drug resistance. The number of chemotherapy courses was 7.8 ±2.1, and the number of chemotherapy courses required for β-hCG to return to normal was5.4 ±1.8. There were 46 patients who were undergoing combination chemotherapy, among which 7 (15.2%) developed drug resistance. The number of chemotherapy courses was 7.4 ±2.0, and the number of chemotherapy courses required for β-hCG to return to normal was 4.8 ±1.6. A statistically significant difference was found in the drug resistance rate between these two subgroups (P < 0.05); however, there was no significant difference between these two subgroups in terms of the number of chemotherapy courses or the number of chemotherapy courses required for β-hCG to return to normal (P > 0.05).
There were 12 FIGO stage III patients who were undergoing single-agent chemotherapy, among which 11 (91.7%) developed drug resistance. The number of chemotherapy courses was 8.4±1.8, and the number of chemotherapy courses required for β-hCG to return to normal was 5.7±1.8. There were 18 FIGO stage III patients who were undergoing combination chemotherapy, among which 3 (16.7%) developed drug resistance. The number of chemotherapy courses was 7.5±2.0, and the number of chemotherapy courses required for β-hCG to return to normal was 4.8±1.8. A statistically significant difference was found in the drug resistance rate between the two subgroups (P < 0.05); however, there was no significant difference between these two subgroups in terms of the number of chemotherapy courses or the number of chemotherapy courses required for β-hCG to return to normal (P > 0.05). There was no discontinuation or abandonment of treatment due to intolerable adverse reactions or any serious adverse reactions leading to death.
A recent study in Canada on low-risk GTN investigated a total of 412 patients and reported a chemotherapy failure rate of 32% for patients with a FIGO/WHO prognostic score of 0–4, and a significantly increased failure rate of 59% for patients with a FIGO/WHO prognostic score of 5–6[5]. Many scholars have debated whether the current staging and scoring system should be modified to a more precise model, so that some susceptible drug-resistant patients could adopt a more effective plan at the beginning of treatment. However, Braga A et al[6]found approximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5-6 could achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors including metastatic disease, choriocarcinoma and pretreatment human chorionic gonadotropin concentration. Our results are consistent with Braga A et al’ study[6]. Monotherapy showed significant advantages in low-risk GTN patients with a FIGO/WHO score of 5–6，with or without lung metastases.