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European Journal of Obstetrics & Gynecology and Reproductive Biology 112 (2004) 9597

How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data
Jozsef Bator, Gyorgy Vegh, Janos Szepesi, Ivan Szigetvari, Jozsef Doszpod, Vilmos Fulop*
Department of Obstetrics and Gynecology, National Health Center, 35 Szabolcs Street, Budapest 1135, Hungary Received 23 November 2002; received in revised form 22 April 2003; accepted 22 April 2003

Abstract Objective: We analyzed human chorionic gonadotropin (hCG) follow-up data of patients with molar pregnancy. Women often do not complete recommended post-disease screening. Our purpose was to determine if continuing follow up of uncomplicated molar cases beyond attaining undetectable hCG levels is necessary for detecting relapse of gestational trophoblastic disease. Study design: One hundred fty patients treated at Hungarian National Health Center were analyzed. Those who developed persistent disease before hCG had become undetectable were excluded from further analysis (n 24; 16%). Results: Among 126 uncomplicated cases, 72 patients (57%) completed follow up, and 54 (43%) discontinued their protocol before it had been completed. Of 120 patients who achieved at least one undetectable hCG level, none had any evidence of relapse. Conclusion: In uncomplicated hydatidiform mole, our analysis indicates that once undetectable serum hCG levels are attained, relapse is unlikely. Although further monthly checks are advisable, the likelihood of recurrence appears very low. # 2003 Elsevier Ireland Ltd. All rights reserved.
Keywords: Gestational trophoblastic disease; Complete and partial hydatidiform mole; Human chorionic gonadotropin; hCG; Follow up

1. Introduction Gestational trophoblastic disease (GTD) is a collective term for different pathologic events arising from human trophoblast tissues. GTD includes partial and complete hydatidiform moles (PM and CM), placental site trophoblastic tumor (PSTT) and choriocarcinoma. The incidence of hydatidiform mole is 13 for 1000 pregnancies. All PM and CM may have recurrence after treatment and can develop into persistent trophoblastic disease (PTD), which is a potentially deadly disorder of fertile women because of its ability of rapid progressiveness, local uterine invasion and leading to early metastases. On the other hand, GTD is one of the most easily cured tumors due to its high sensitivity to chemotherapic agents [17]. Furthermore the reproductive outcome is excellent after GTD. The majority of patients treated with chemotherapy for GTD who wish to retain childbearing capabilities are able to conceive after the recovery, and still have a normal future reproductive outcome [8,9]. All GTD have a high production of human chorionic gonadotropin (hCG), which can be measured from both the serum and the urine. The serum b-hCG is a well-known excellent indicator for following the process of the disease,
* Corresponding author. Tel.: 36-1-350-47-60; fax: 36-1-350-47-38. E-mail address: batorfijozsef@hotmail.com (V. Fulop).

checking the effectiveness of the treatment and recognizing relapse, progression and malignant transformation of molar pregnancies. The generally recommended follow up for patients with hydatidiform mole includes serial weekly hCG checks after molar evacuation, then a continued monthly follow up varying from 3 to 6 months once undetectable titer is attained. Although this protocol is meant to ensure relapse is detected, women often do not complete the recommended post-disease screening [1012]. In this study, we analyzed hCG follow-up data of 150 patients treated at Hungarian National Health Center with either complete or partial hydatidiform mole. We calculated how often patients with molar pregnancy do not complete the entire recommended interval of follow up. Our purpose was to determine if continued follow up of uncomplicated molar cases beyond attaining undetectable serum hCG levels is necessary in order to detect the relapse of gestational trophoblastic disease.

2. Materials and methods One hundred fty randomly selected patients with molar pregnancy were analyzed retrospectively regarding the serum hCG levels following molar evacuation. Patients were treated and followed at Hungarian National Health Center

0301-2115/$ see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0301-2115(03)00274-4

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J. Batorfi et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 112 (2004) 9597

between 1998 and 2001. Among more than 500 patients who were registered in this period with complete or partial hydatidiform mole, the rst 150 were selected for analysis in alphabetical order avoiding selection bias. We have collected all the information about patients data, histological diagnosis of their presenting GTD, details of patients participation in the recommended follow up, pre-evacuation serum hCG titers and the number of weeks until serum hCG became undetectable. The generally used protocol for patients follow up was the following. In cases of CM, it was recommended to check serum hCG levels weekly until undetectable three consecutive weeks then monthly until undetectable six consecutive months. For patients with PM the monthly hCG checking was recommended only until undetectable three consecutive months if serum hCG became negative within 7 weeks after curettage. Otherwise the same protocol was used as for patients with complete mole. All patients were fully informed of serious risks of gestational trophoblastic diseases emphasizing the importance of exact post-disease monitoring. They were warned about the riskiness of premature discontinuation of their follow up. The statistical signicance of data was evaluated by using Students two-tailed t-test. The level of signicance was assigned at P < 0:05.

Fig. 1. Patients participation in the follow-up protocol.

3. Results The age of the patients ranged from 15 to 51 years with the mean age of 28.8 (S.D., 7.6) years. The histological diagnosis was complete mole in 94 cases (63%) and partial mole in 56 cases (37%). We compared complete and partial mole regarding serum hCG values before and after molar evacuation. There were signicant differences in the pre-evacuation serum hCG level (mean: 275,737 IU/l for CM and 96,743 IU/l for PM; P 0:04) and in the number of weeks until hCG became undetectable in uncomplicated cases (mean: 9.7 weeks for CM and 6.5 weeks for PM; P < 0:01). These data were consistent with previously reported results [13,14]. Among 150 randomly selected cases, 126 patients (84%) had a spontaneous regression of serum hCG titers after molar evacuation (uncomplicated cases). Twenty-four (16%) developed persistent trophoblastic disease (PTD) requiring chemotherapy and in certain cases further surgical interventions. The frequency of PTD was 23.4% in CM (n 22) and 3.6% in PM (n 2). PTD is a dangerous state with the possibility of developing uterine invasion and/or metastases. According to our opinion, it is not enough to follow patients with PTD until only undetectable hCG level is reached. A careful, exact, long-time monitoring is required for them until permanent remission can be diagnosed. That is why patients who developed persistent trophoblastic disease before serum hCG had become undetectable were excluded from our

further analysis. The remaining analysis was performed only on 126 patients with partial or complete mole with a continuously decreasing serum hCG level after molar evacuation (72 cases of CM and 54 of PM). Our purpose was to determine whether among those patients who achieved undetectable serum hCG levels there was any subsequently relapsed case or not. Seventy-two patients (57%) completed follow up for their disease, and 54 discontinued their protocol before it had been completed (43%). Patients who did not complete recommended control examinations were lost in six cases (5%) before achieving undetectable weekly hCG values and after it in 48 cases (38%) (Fig. 1). In ve patients (4%), the reason for discontinuing follow up was their conceiving before completion recommended control serum hCG checks. All of them had attained undetectable hCG values before the conception. Of the 120 patients who achieved at least one undetectable serum hCG level, none had any evidence of relapse of persistent trophoblastic disease.

4. Comment It is well recognized that persistent trophoblastic disease can be developed from both complete and partial hydatidiform mole [15]. In order to detect the possibility of relapse, exact serum b-hCG follow up of these patients is one of the most important steps in the management of gestational trophoblastic diseases. Our data revealed that 43% of patients prematurely terminated their follow up before the usual 36 months. Moreover, six patients were lost to follow up before their serum hCG level fell to negative titers. Despite giving complete information to all patients including potentially deadly feature of their disease, we were not able to improve the frequency of completely followed cases. Importantly, among our randomly selected cases none of the patients who achieved negative hCG titers (n 120) had a relapse of GTD.

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Previously, our workgroup has analyzed hCG follow-up data of patients with molar pregnancy in collaboration with Harvard Medical School. Utilizing New England Trophoblastic Disease Center Database, among 320 randomly selected uncomplicated molar cases, none of the patients had relapse of their GTD after achieving undetectable hCG follow-up values [15]. Although current recommendation for follow up is meant to ensure relapse is detected, it appears that the risk for recurrence is exceedingly low after attaining undetectable hCG levels. Our data show a bad acceptability of the relatively longusually more than half yeartime of monitoring. A lot of patients lost their follow up before it had been completed. It is possible that given such a low risk for recurrence, a shorter post-evacuation screening could be acceptable for the uncomplicated molar cases as long as negative hCG levels are attained. In patients with uncomplicated hydatidiform mole, our analysis indicates that once undetectable serum hCG levels are attained relapse is unlikely. The follow up of uncomplicated PM and CM with weekly serum hCG levels until negative titers seems to be safe, in addition may improve the effectiveness of screening because of its better acceptability. Although further monthly checks are advisable, the likelihood of recurrence appears very low.

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