It was stated by FIGO cancer report and NCCN guideline that prophylactic chemotherapy should be limited to special situations [1, 7]. Our results found that the proportion of high-risk GTN in P-chem group was higher than that in control (11.1% vs 6.3%) although the difference was not significant, which also supported that P-chem should be administered in cautious. Nevertheless, P-chem may still be considered for HM in some patients deemed at high risk for malignant transformation [1, 7], since it was reported that P-Chem was associated with about two-thirds reduction in the incidence of GTN compared with control group . Up to date, no optimal regimen for P-chem has been defined. Usually, MTX or Act-D is suggested for P-chem . But in china, 5-FU is also prescribed as P-chem agent based on the theory that chemotherapy agents that have known activity against GTN may prevent progression to GTN . The course of chemotherapy was not clearly defined in previous study and varied in our study. Most studies administered one course [8, 10, 20–21], while Fasoli administered three courses of MTX . The regimen and timing for P-chem were also varied, including 5-day Act-D, 5-day or 8-day MTX and single-dose Act-D [8–10, 15, 21–25]. Although most studies administered P-chem before or during evacuation of HM [8, 10, 21], it carried the inherent risk of over-treating for those patients with histological confirmed non-molar hydropic abortions . In present study, P-chem was performed within 1 week after evacuation, which is similar with previous studies that administered P-chem within 1 week or 3 weeks after evacuation [9, 20, 27].
The interval from pervious HM to GTN is one component in WHO scoring system since 2000 . In our study, the diagnosis of GTN was made approximately 25 days later in the P-Chem group (including high-risk and low-risk GTN) than control, which is consistent with previous report . But hCG level in P-Chem group was lower than control, which might offset the role of delayed diagnosis. In a result, WHO risk score was similar in both groups, which might further determine the treatment outcome of postmolar GTN.
Due to limited contributing data, drug resistance following P-chem was inadequately evaluated in previous study . Kim et al deduced that P-chem might increase resistance to subsequent chemotherapy for GTN, because they found that P-chem group needed more chemotherapy courses than control (2.5 vs 1.4, p < 0.005) . However, their data suggested that both 4 GTN in P-chem group and 10 GTN in control achieved complete remission following initial treatment for GTN. Due to the small sample in Kim’s study, the evidence is inadequate to draw a definite conclusion. On the contrary, Uberti et al analyzed 265 patients with high-risk HM, and found that P-chem didn’t increase resistant rate or chemotherapy courses of postmolar GTN . Consistent with Uberti’s reports, our results also found that P-Chem didn’t increase chemotherapy cycles and resistant rate of chemotherapy in both low risk and high risk GTN. Due to the different first-line agent used in low risk GTN, resistant rate of single-agent chemotherapy was further compared and no difference was revealed. Combined previous studies with our data, P-chem don’t contribute to drug resistance for postomar GTN treatment.
As we know, the drugs used for P-Chem are also used for GTN treatment, so it is supposed that an alternative agent could be used for following low-risk GTN in order to prevent resistance to first-line chemotherapy . But, Uberti’s results revealed that alternative agent did not reduce resistant rate, after we further calculated their raw data (25.0% vs 33.3%, p = 0.645) . Similar with Uberti’s study, our results found that alternative agent as first-line chemotherapy did not reduce the resistant rate of low-risk postmoalr GTN. Moreover, resistant rate of single-agent chemotherapy and total chemotherapy cycles in patients treated by alternative agent were also similar with that treated by agent same as P-chem, even among 22 patients who were administered MTX as P-chem. But interestingly, further statistics revealed that alternative agent reduced about 1.6 chemotherapy cycles to achieve hCG normalization when 24 low-risk GTN were included, and drugs different from MTX reduced 1 chemotherapy cycle when only 22 patients received MTX for P-chem were included. These results indicated that alternative agent had the potential of increasing chemotherapy response of low-risk GTN, despite that the drug resistant rate didn't change by alternative agent.
Present study focuses on the effect of P-chem and alternative agent on the chemotherapy response of subsequent postmolar GTN, based on a relatively large number of cases.
However, our study was conducted in single GTD center and the data was collected retrospectively.
The limited sample size contributed to the relatively weak statistical power of analysis,due to the rare status for postmolar GTN.
Thus, our results should be interpreted with caution, and further prospective randomized control trials are recommended to provide sufficient evidences about the use of P-Chem in clinical practice.