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How long should patients be followed after molar pregnancy?Analysis of serum hCG follow-up data

Jozsef Batorfi, 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 beyondattaining undetectable hCG levels is necessary for detecting relapse of gestational trophoblastic disease. Study design: One hundred fifty

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 anyevidence 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 tropho-

blastic 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 poten-

tially 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 chemothera-

pic 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,

checking the effectiveness of the treatment and recognizing

relapse, progression and malignant transformation of molarpregnancies. 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 unde-

tectable 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 fifty 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

European Journal of Obstetrics & Gynecology and

Reproductive Biology 112 (2004) 9597

* Corresponding author. Tel.: 36-1-350-47-60; fax: 36-1-350-47-38.

E-mail address: batorfijozsef@hotmail.com (V. Fulop).

0301-2115/$ see front matter # 2003 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/S0301-2115(03)00274-4

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between 1998 and 2001. Among more than 500 patients who

were registered in this period with complete or partial

hydatidiform mole, the first 150 were selected for analysis

in alphabetical order avoiding selection bias. We have

collected all the information about patients data, histolo-

gical diagnosis of their presenting GTD, details of patients

participation in the recommended follow up, pre-evacuationserum 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 consecu-

tive 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 gesta-

tional 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 significance of data was evaluated by using

Students two-tailed t-test. The level of significance was

assigned at P < 0:05.

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 partialmole in 56 cases (37%).

We compared complete and partial mole regarding serum

hCG values before and after molar evacuation. There were

significant 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 devel-

oping 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 eva-

cuation (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 five patients (4%), the

reason for discontinuing follow up was their conceiving

before completion recommended control serum hCGchecks. 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 hydatidi-

form 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 com-

plete 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 randomlyselectedcases noneof the patients who achieved

negative hCG titers (n 120) had a relapse of GTD.

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

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

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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 Tropho-

blastic 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 mon-

itoring. 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 uncom-

plicated 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 like-

lihood of recurrence appears very low.

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