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Diagnostic and therapeutic curettage in gestational trophoblastic disease
Diagnostic and therapeutic curettage in gestational trophoblastic disease John B. Schlaerth, MD, C. Paul Morrow, MD, and Maria Rodriguez, RN Los Angeles, California From June 1976 through June 1989, 37 nonconsecutive patients underwent uterine curettage during the course of their gestational trophoblastic disease. In 22 patients (59%) trophoblastic tissue was obtained. Three (8.1 %) patients sustained a uterine perforation during the procedure. In six patients curettage was performed for bleeding. There were six patients curetted during assessment for metastatic trophoblastic disease. Twenty-eight patients underwent curettage for the presumed diagnosis of non metastatic gestational trophoblastic disease. In retrospect, four of these women (14.3%) had insufficient criteria for the diagnosis of gestational trophoblastic disease. Of the remaining 23 patients, four (17.4%) went into clinical remission without further treatment. Ten patients (43.5%) had a transitory decline in serum ~-human chorionic gonadotropin levels that subsequently rose or plateaued. Six patients (26.1 %) showed no effect from the curettage on their serum ~-human chorionic gonadotropin trend during a short period of observation. Three patients (13.0%) with nonmetastatic gestational trophoblastic disease were not observed for a possible therapeutic effect after curettage. Thus, in only 4/20 (20%) women with nonmetastatic trophoblastic disease was a therapeutic effect from curettage shown. (AM J OBSTET GVNECOL 1990;162:1465-71.)
Key words: Curettage, gestational trophoblastic disease, effectiveness, risks
Uterine curettage has traditionally been regarded as important for diagnostic and therapeutic reasons in the assessment of women with gestational trophoblastic disease. I -3 In fact repeated curettages have been a common practice! Yet there has been little critical evaluation of curettage in this setting!-6 For this reason a retrospective review of the uterine curettages performed in women presumed to have gestational trophoblastic disease at our institution was undertaken. The purpose of this study is to examine the advantages and disadvantages of curettage in women with gestational trophoblastic disease.
Material and methods The medical records of all patients who underwent uterine curettage during follow-up for hydatidiform mole or suspected gestational trophoblastic disease at Los Angeles County-University of Southern California Women's Hospital were reviewed. Twenty women were curetted during the 46-month period from June 1976 through March 1980. Two of these women had a gesFrom the Division of Gynecologic Oncology. Department of Obstetrics and Gynecology, University of Southern California School of Medicine. Presented at the Fifty-sixth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Coronado, California, September 17-21,1989. Reprint requests: John B. Schlaerth, MD, Los Angeles CountyUniversity of Sou/hem Califomia Women's Hospital, 1240 North Mission Road, Room L903, Los Angeles, CA 90033. 6/6/20739
Table I. Uterine curettage results and serum R>-hCG levels in patients with nonmetastatic trophoblastic disease Curettage specimen
No. of patients
Gestational trophoblastic disease Trophoblastic cells Chorionic villi Normal endometrial tissue
6
Serum {3-hCG (mIV/ml) Mean
11,292
I
Range
1,220-16,362
6
4,716.5
259-15,947
3
2,396.7
140-4,500
9
7,019.3
14-20,900
tational choriocarcinoma not preceded by a hydatidiform mole. Interest in curettage for such patients waned during the next 7 years. Another 17 women underwent curettage during follow-up for hydatidiform mole in the 20-month period from November 1987 through June 1989. During these two time periods a repeat curettage was performed during the follow-up for hydatidiform mole if (1) R>-human chorionic gonadotropin serum (R>-hCG) levels plateaued or rose or (2) excessive uterine bleeding occurred. The clinical records were reviewed for initial management of the hydatidiform mole, the presence of bleeding, the size of the uterus, the trend of serum R>hCG levels before the curettage, the level of serum R>1465
1466 Schlaerth, Morrow, and Rodriguez
June 1990 Am J Obstet Gynecol
Table II. Uterine curettage performed for excessive bleeding from gestational trophoblastic disease Serum f3-hCG Patient
mIUlml
I
Pathologic histology
Trend curettage
Uterine size
Gm
18
P. C.
1080
Falling
Normalt
D.D.
6200
Falling
Large:j:
M.H.
1800
None*
L. M.
77800
A.P.
278
I
Days after mole-pregnancy
Tissue
Outcome
Atypical trophoblasts
32
Lost to follow-up
200
Decidua, blood
31
Large
30
Hydatidiform mole
16
Spontaneous remIssIon
None*
Large
230
Hydatidiform mole
7
Falling
Normal
3
Endometrium
31
Spontaneous remission Spontaneous remIssIon Chemother~p.y;
P. F.
Normal
None*
3880
9
Choriocarinoma
remIssIon Chemotherapy; hysterecto~~; remIssIon
197
Other
Blood transfusion
Lung metastasis Perforation
*Single value (?). t<8 Weeks' gestational size. :j:>8 Weeks' gestational size.
Table III. Uterine curettage performed in patients with metastatic trophoblastic disease Pathologic histology
Serum f3-hCG Patient
L. G. M. A. P. S. S. G.A. M.L.
J.
mIUlml
I
870 665 278 1070 86400 550
Trend at curettage
Uterine size
Gm
Plateau Plateau Declining Plateau None Plateau
Normal* Normal Normal Normal Larget Normal
Fragments 18 3 2 7 2
I
Tissue
Days after mole-pregnancy
Endometrium Endometrium Endometrium Hydatidiform mole Endometrium Decidua
48 40 31 59 79 41
*<8 Weeks' gestational size. t>8 Weeks' gestational size.
hCG at the curettage, and for evidence of metastasis. Further, the quantity of the curettage specimen and the histologic descriptions were analyzed. A uterus was considered enlarged if a sounding exceded 10 cm or the estimate of size was >8 weeks' gestational size. Persistent gestational trophoblastic disease was diagnosed by a rise or plateau in serum (3liCG levels or by the appearance of metastasis. A rising trend in serum (3-hCG levels was defined as doubling in value over a 2-week period. A plateau in hCG levels was generally considered to be present when no decrease in serum (3-hCG level was apparent during 3 weeks of observation and any increase was insufficient to qualify as a rising trend. Assessment for metastasis included history and physical examination, liver func-
tion tests, chest roentgenogram, pelvic ultrasonographic examination, and computerized tomography of the chest, abdomen, brain and pelvis. Earlier patients underwent radioisotope scans of the brain and liver and pelvic angiography. The uterine curettage specimen was considered positive if a histologic diagnosis of'a gestational trophoblastic disease or trophoblastic cells were detected, otherwise it was considered negative for diagnostic purposes. Last, the details in management and clinical outcome were determined for all patients. Results
General observations. The yield from the curettages were analyzed for the 24 women with non metastatic
Curettage in gestational trophoblastic disease
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Table IV. Uterine curettage in patients with unsubstantiated trophoblastic disease in retrospect (immediate precurettage titer hCG showed decline*) Serum {3-hCG Patient
mIUlml
I
Pathologic histology
Trend at curettage
Uterine sIze
Tissue
Days after mole-pregnancy
5
Trophoblastic
45
Atypical trophoblastic Chorionic villi
32
Endometrium
49
I
Gm
E. C.
1400
Plateau
Larget
P. C.
1080
Plateau
Normal:j:
18
R. F.
133
Plateau
Normal
3
K. B.
1640
Rise
Normal
76
Outcome
Hysterectomy for performation. remission Lost to follow-up Spontaneous remission Spont~neous remiSSion
*Value not received until after curettage. t>8 Weeks' gestational size. :j:<8 Weeks' gestational size.
Table V. Uterine curettage followed by spontaneous remission of nonmetastatic trophoblastic disease Pathologic histology
Serum {3-hCG Patient
mIUlml
R. M.
643
B. C.
25200
V. M.
5430
R. D.
259
I
Trend at curettage
Uterine size
Gm
Rise
Normal*
Plateau
Larget
16
Rise
Normal
2
Plateau
Normal
8
I
Tissue
Days after mole-pregnancy
Trophoblasts
53
Hydatidiform mole Bizarre trophoblasts Trophoblasts
62 42 88
Outcome
Spontaneous in 20 days Spontaneous in 30 days Spontaneous in 42 days Spontaneous in II days
remission remission remission remission
*<8 Weeks' gestational size. t>8 Weeks' gestational size.
trophoblastic disease (Table I). Fifteen of 24 (62.5%) of those patients exhibited some aspect of trophoblastic histology. The uterine sizes were analyzed in reference to the diagnostic yield on the curettages. The curettings from eight of 12 (66.7%) large uteri contained trophoblastic elements. The curettings from 25 normal-sized uteri showed trophoblastic tissue in 13 (52%). Bleeding. Six patients underwent uterine curettage because of significant bleeding (Table II). Four of these women were clinically considered to have retention of molar tissue after evacuation. Two of these patients were evacuated at our institution. one (P. C.) by suction and sharp curettage to complete spontaneous abortion of the hydatidiform mole and the other (L. M.) underwent elective suction and sharp curettage for an intact hydatidiform mole. No details of primary management are known for the other two women (M. H., D. D.). One woman with metastatic postmolar trophoblastic disease and one woman with postabortal choriocarcinoma also underwent curettage. It should be noted
that this last patient sustained a uterine performation that led to laparotomy and hysterectomy. Persistent trophoblastic disease Metastatic. Six patients underwent uterine curettage as part of their assessment for metastatic trophoblastic disease (Table III). The preceding gestation in five patients was a hydatidiform mole and a tubal pregnancy in one (G. A.). One patient (A. P.) with metastasis was first seen with bleeding and is included under both groups of patients. N onrnetastatic. A total of 28 women underwent uterine curettage for presumed nonmetastatic postmolar trophoblastic disease on the basis of the trend of serum hCG levels. Two women with serum hCG trends suggesting postmolar trophoblastic disease also were first seen with bleeding and are included in Table II. :I'li . Despite a trend of serum l3-hCG levels to substantIate the diagnosis of non metastatic postmolar trophoblastic disease. four patients had a significant drop in l3-hCG level in the serum specimen drawn immediately before curettage (Table IV). Therefore. in retrospect the di-
1468 Schlaerth, Morrow, and Rodriguez
June 1990 Am J Obstet Gynecol
Table VI. Uterine curettage followed by a nonsustained fall in serum j3-hCG levels in patients wIth non metastatic trophoblastic disease Serum f3-hCG Patient
mIU I ml
I Trend at
Pathologic histology
curettage
Uterine size
I
Gm
S.W. T. C.
140 1170
Plateau Rise
Normal* Normal
M.M.
5340
Plateau
Larget
15
H. S.
16362
Rise
Large
225
T. D.
15700
Rise
Normal
3
S. J.
V. M. E. S.
3380 20900 2550 1270
Plateau Plateau Rise Plateau
Normal Normal Normal Normal
24 1 2 4
L.R.
15947
Plateau
Large
A.A.
5 3
Serum f3-hCG (mIUlml) Day after mole-pregnancy
Tissue
Chorionic villi Necrotic trophoblasts Hydatidiform mole Hydatidiform mole Hydatidiform mole Trophoblasts Endometrium Chorionic villi Hydatidiform mole Trophoblasts
730
At nadir
I
At start of treatment
I
Trend
32 29
18 273
37 648
Plateau Rise
29
520
645
Plateau
26
2130
7100
Rise
39
378
915
Rise
42 57 37 34
638 8933 2300 834
1190 11900 6900 930
Plateau Plateau Plateau Plateau
26
15100
16600
Plateau
*<8 Weeks' gestational size. t>8 Weeks' gestational size.
Table VII. Uterine curettage without effect in patients with nonmetastatic trophoblastic disease Serum f3-hCG Patient
mIUlml
I
Pathologic histology
Trend at curettage
Uterine Size
Gm
J.w.
14 6140
Plateau Plateau
Normal* Normal
3 2
B. A.
2920 5700 2640 4030
Rise Rise Plateau Rise
Normal Larget Large Normal
2 1 6 4
L. M.
T. M.
N.V. C.M.
I
Tissue
Endometrium Necrotic cellular debris Blood Blood Trophoblasts Endometrium
Serum f3-hCG (mIU Iml) Days after mole-pregnancy
At treatment
I
Trend
152 31
17 7300
Plateau Plateau
30 47 43 36
4310 16000 6820 13100
Plateau Rise Rise Rise
*<8 Weeks' gestational size. t>8 Weeks' gestational size. agnosis of postmolar trophoblastic disease at the curettage could not be sustained. The diagnostic and therapeutic effects of these curettages are also questionable. However, one patient (E. C.) did have an invasive mole. Another patient (P. C.) is also included among those curetted for bleeding in Table I. After curettage four patients went into complete remission without further treatment. There was no clinical suspicion noted that incomplete evacuation of the hydatidiform mole had occurred in these patients (Table V). Ten patients had a decline in serum j3-hCG values after curettage that was not sustained (Table VI). All these women subsequently had a serum j3-hCG trend again indicating postmolar trophoblastic disease. All were successfully treated to remission with chemotherapy. Six patients underwent curettage at the time of diagnosis of non metastatic gestational trophoblastic dis-
ease and showed no effect from this procedure on their disease as evidenced by a continuous plateau or rise in serum j3-hCG levels during a period of observation afterward (Table VII). All these women were treated to successful remission with chemotherapy. Four women with nonmetastatic trophoblastic disease had no postcurettage follow-up, which rendered them unevaluable for therapeutic effect from this procedure (Table VIII). One patient (P. F.) included here was also considered among the patients who were first seen with bleeding (Table II).
Comment The curettages done for bleeding were not elective procedures and, as mentioned previously, four of these clinical situations were considered incomplete molar evacuations. But the presence of bleeding, the declining trend in serum j3-hCG levels, molar tissue in 2/4 patients, and spontaneous remission after curettage fit
Curettage in gestational trophoblastic disease
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Table VIII. Uterine curettage without follow-up in patients with nonmetastatic trophoblastic disease Serum {3-hCG
Pathologic histology
Trend at curettage
Uterine size
Gm
4500
Rise
Large
350
s.
4500
Plateau
Normal
T. G.
17800
Rise
P. F.
3880
None
Patient
mIUlml
A.G. M.
I
I
Tissue
Days after mole-pregnancy
36
2
Blood, endometrium Trophoblasts
Normal
0
Endometrium
27
Normal
9
Choriocarcinoma
Outcome
Chemotherapy, remission Chemotherapy, remission Perforation, laparotomy, lost to follow-up Perforation, hysterectomy, chem?t~erapy, remiSSion
28
197
Table IX. Therapeutic effect of curettage in nonmestatic trophoblastic disease Serum {3-hCG (mIUlml)
Remission with curettage No remission with curettage
No.
Mean
4
7883
16
6513
well with the concept of incomplete abortion as opposed to nonmetastatic postmolar trophoblastic disease. Two of these women had their initial evacuation at our institution. During the time periods of this study 140 patients received initial management of their molar pregnancy at Women's Hospital for a 2/140 (1.4%) incomplete evacuation rate. In this series 21 of37 women (56.8%) had curettages that revealed trophoblastic tissue. This experience is similar to the 46% and the 70% positive curettage rate reported in the two series by Berkowitz. 5 • 6 Only nine (24.3%) women had a sufficient curettage specimen to allow a histologic diagnosis (eight hydatidiform moles and one choriocarcinoma). Nine women (24.3%) had trophoblastic tissue that, although insufficient in amount for histologic diagnosis would still allow analysis for prognostic features such as those described by Hertig7 and Deligdisch. B Inasmuch as all patients who were not lost to follow-up in this series had remission of their disease with curettage, chemotherapy, hysterectomy, or a combination of these modalities, it is difficult to make a statement with regard to the importance of histologic diagnosis in clinical management. Berkowitz5 found that one course of chemotherapy with methotrexate and citrovorum factor was definitive therapy for 95% of trophoblastic disease patients who had no trophoblastic tissue in the curettage specimen, whereas 59% of women with trophoblastic tissue in their curettages required more than one course of ther-
-'
Positive curettage
Range
No.
259-25200
4/4
14-20900
9/16
I
% 100
56.25
apy for clinical remission. It has been the practice at our institution to treat such women with weekly or biweekly courses of chemotherapy until one course has been given after a normal serum ~-hCG level. This practice and the fact that several different chemotherapy regimens have been used in these women does not allow comparison on this point with the Berkowitz5 senes. With the use of a serum ~-hCG level of 50,000 mIU 1ml Berkowitz5 found a rough correlation with trophoblastic tissue in the curettage specimen and multiple courses of chemotherapy. However, in this present series (Table I) there was no apparent correlation between trophoblastic tissue in the curettings and serum ~-hCG levels in patients with nonmetastatic trophoblastic disease. Therefore as a predictor of response, serum ~-hCG levels seem more applicable clinically than diagnostic curettage results. In our small experience with uterine curettage in metastatic gestational trophoblastic disease no benefit of curettage on an elective basis could be shown. It is likely that the tradition for repeated curettages is based on older experiences with patients, such as those in Table V, in whom a convincing therapeutic effect was apparent after a plateau or rise in serum 13hCG levels. The analysis in this report did not disclose how these four patients differed from those patients whose nonmetastatic trophoblastic disease persisted after curettage (Table IX) other than that all their cu-
1470 Schlaerth, Morrow, and Rodriguez
rettages were positive for trophoblastic tissue versus a 9/16 (56.25%) positive rate for the others. It is probable that most or all their trophoblastic disease was located in the superficial myometrium and the endometrium, both within reach of the curette. 1 In this regard diagnostic imaging techniques could prove helpful in the selection of optimal candidates for therapeutic curettage. Berkowitz5 has reported that ultrasonography can be helpful in the prediction of a positive curettage 73.9% (17/23) of the time. The intriguing observation that curettage may be definitive therapy in 20% (4/20) of patients with nonmetastatic trophoblastic disease must be tempered by the fact that all three patients (8.1 %) who sustained a uterine perforation required laparotomy and two underwent hysterectomy. These three curettages were performed by third-year resident physicians with staff physicians in attendance. It is well documented that myometrial invasion, perforation, and hemoperitoneum can all occur spontaneously with trophoblastic tumors. This process renders elective curettage for postmolar gestational trophoblastic disease a procedure with some risk to fertility. This is of particular concern because most of these women are young with a current interest in having children. In view of these facts, unless a group to benefit therapeutically from curettage can be clearly identified, there does not appear to be a significant place for elective curettage in women with postmolar gestational trophoblastic disease. REFERENCES 1. Bagshawe KD. Surgery in the diagnosis and treatment of trophoblastic tumors. In: Choriocarcinoma. Baltimore: Williams and Wilkins, 1969:133-41. 2. Hilgers RD, Lewis]L. Gestational trophoblastic neoplasia. GynecolOncol 1974;2:460-75. 3. Hammond Cb, Weed] C, Currie]L. The role of operation in the current therapy of gestational trophoblastic disease. AM] OBSTET GYNECOL 1980;136:844-58. 4. Lao TTH, Lee FHC, Yeung SSL. Repeat curettage after evacuation of hydatidiform mole. Acta Obstet Gynecol Scand 1987;66:305-7. 5. Berkowitz RS, Desai U, Goldstein DP, Driscoll SG, Marean AR, Berstein MR. Pretreatment curettage-a predictor of chemotherapy response in gestational trophoblastic neoplasia. Gynecol Oncol 1980;10:39-43. 6. Berkowitz RS, Birnholz ], Goldstein DP, Bernstein MR. Pelvic ultrasonography and the management of gestational trophoblastic disease. Gynecol OncoI1983;15:403-12. 7. Hertig A], Sheldon WHo Hydatidiform mole: a pathologicoclinical correlation. AM] OBSTET GYNECOL 1974;53:124. 8. Deligdisch L. Driscoll SG, Goldstein DP. Gestational trophoblastic neoplasma: morphologic correlater of therapeutic response. AM] OBSTET GYNECOL 1978;130:801-6. Editors' note: This manuscript was revised after these discussions were presented.
June 1990 Am J Obstet Gynecol
Discussion
R. SMITH, Seattle, Washington. Drs. Schlaerth and Morrow have reviewed for us the Los Angeles County Hospital experience with pretreatment curettage in the management of gestational trophoblastic neoplasia over the past 13 years. The purpose of their review was to assess the value of this traditional modality. The data base consists of 37 patient records that detail curettage procedures in the course of gestational trophoblastic neoplasia evaluation. Six were done for bleeding, six for evaluation of metastatic disease, and 27 for assessment of nonmetastatic disease. Of the six done for bleeding, four were because of clinically obvious retained products after molar evacuation. In each case, bleeding was controlled and spontaneous remission ensued. In the fifth case, bleeding was controlled, but metastatic disease prompted chemotherapy. In the sixth case, uterine perforation prompted hysterectomy before chemotherapy. No benefit, therapeutic or prognostic, was achieved in the five instances in which curettage was performed as part of the workup of metastatic gestational trophoblastic neoplasia. Four of 27 who underwent curettage during evaluation of nonmetastatic gestational trophoblastic neoplasia required no further treatment. No therapeutic or prognostic benefit was noted in the remaining 23, and one required hysterectomy for uterine perforation. Nine of 37 (24.3%) benefitted either through control of bleeding or eradication of disease. Two of 37 (5.4%) required hysterectomy for control of bleeding associated with postcurettage uterine perforation. Twentysix of 37 (70.3%) derived no benefit whatsoever. All were ultimately cured of their disease. The authors conclude that there is no clear indication for uterine curettage in the management of postmolar gestational trophoblastic neoplasia, except in the bleeding patient with evidence of retained tumor. One must reconcile this advice with the recommendations of our colleagues in gynecologic pathology who, although not always in agreement with one another with regard to interpretation of an individual case, do find that the morphologic criteria found in the 60% or so of positive curettage specimens provide useful prognostic information. Similarly, one must reconcile this advice with the recommendations of experienced clinicians who find that debulking of nonmetastatic gestational trophoblastic neoplasia by curettage may eliminate the need for chemotherapy in some patients and reduce the total number of treatment courses in others. We are aided in our reconciliation by the abundance of data worldwide that show that the extraordinary specificity and sensitivity of the radioimmunoassay for the ~-hCG far exceeds that of microscopic histopathology, immunochemistry, and diagnostic imaging in establishing both the diagnosis of gestational trophoDR. MICHAEL
Volume 162 Number 6
blastic neoplasia and its response to treatment at no patient risk. It is similarly abundantly clear that the success of systemic chemotherapy guided by serial ~-hCG levels far exceeds that of surgical extirpation alone with comparable, or perhaps less, patient risk. Chemotherapy is clearly the gold standard, with surgery assuming an adjuvant role for resection of chemotherapy-resistent metastases or for elective hysterectomy in the patient with no interest in subsequent fertility. The day before I received this manuscript, as if on cue a young woman 5 months after evacuation of a mole was referred to me. She had undergone two postevacuation curettage procedures before referral because of plateauing and subsequent elevation of her ~-hCG titers even though her initial evacuation was thought to be complete and the first curettage was negative. She has since responded completely to three courses of methotrexate-two given while her titer was elevated and the final given after her titer returned to normal. In 1981, Drs. Schlaerth and Morrow l helped us better understand the ~-hCG regression curve, and today it is the role of uterine curettage in this disease. I look forward to their continued contribution to our understanding of this disease. I have but one question for Dr. Schlaerth. If confronted with heavy bleeding in a young patient with postmolar gestational trophoblastic neoplasia and a normal sonogram or magnetic resonance imaging (MRI), how would you proceed? REFERENCES I. Schlaerth SB, Morrow CP, Kletsky OA, et al. Prognostic characteristic of the serum radioimmunoassay beta subunit human chorionic gonadotropin titer regression curve following molar pregnancy. Obstet Gynecol 1981 ;58:478.
Curettage in gestational trophoblastic disease
1471
DR. HISHAM K. TAMIMI, Seattle, Washington. We have used intraoperative ultrasonography after the evacuation of 20 molar pregnancies in the past 5 years. The only patient who required chemotherapy was one with lung metastasis. I welcome your comments about the potential for this technique to minimize the need of repeat curettage and even to reduce the need for chemotherapy. DR. JOSEPH OLIVER, Pasadena, California. When do you allow these patients to become pregnant again? Did amenorrhea or Asherman's syndrome develop in any of your patients because of curettage? DR. SCHLAERTH (Closing). Dr. Smith asked what I would do about a patient with heavy bleeding from postmolar gestational trophoblastic disease if she had a sonogram and MRI that revealed nothing suspicious. In one such patient, we did a curettage and the sonogram turned out to be a false-negative one, as it is in this setting from time to time. I have little information about the MRI in this setting. It takes a rather long time to do an MRI, and heavy bleeding may not allow that. The bottom line here is that the clinical situation would dictate what I would do. With heavy bleeding, my first response would be curettage. Dr. Tamimi, your question about intraoperative ultrasonography is part of a larger question of the role played by imaging and endoscopy in the identification of patients who might be cured with curettage alone. We continue to search for solutions to the dilemmas our study has shown and imaging techniques may be the answer. Dr. Oliver, by and large, for patients with non metastatic disease, we ask for a I-year interval before they become pregnant again. I am not aware of any of our patients in whom Asherman's syndrome developed subsequent to curettage. However, our long-term follow-up, as I am sure you realize, is poor.
Key words: Curettage, gestational trophoblastic disease, effectiveness, risks
Uterine curettage has traditionally been regarded as important for diagnostic and therapeutic reasons in the assessment of women with gestational trophoblastic disease. I -3 In fact repeated curettages have been a common practice! Yet there has been little critical evaluation of curettage in this setting!-6 For this reason a retrospective review of the uterine curettages performed in women presumed to have gestational trophoblastic disease at our institution was undertaken. The purpose of this study is to examine the advantages and disadvantages of curettage in women with gestational trophoblastic disease.
Material and methods The medical records of all patients who underwent uterine curettage during follow-up for hydatidiform mole or suspected gestational trophoblastic disease at Los Angeles County-University of Southern California Women's Hospital were reviewed. Twenty women were curetted during the 46-month period from June 1976 through March 1980. Two of these women had a gesFrom the Division of Gynecologic Oncology. Department of Obstetrics and Gynecology, University of Southern California School of Medicine. Presented at the Fifty-sixth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Coronado, California, September 17-21,1989. Reprint requests: John B. Schlaerth, MD, Los Angeles CountyUniversity of Sou/hem Califomia Women's Hospital, 1240 North Mission Road, Room L903, Los Angeles, CA 90033. 6/6/20739
Table I. Uterine curettage results and serum R>-hCG levels in patients with nonmetastatic trophoblastic disease Curettage specimen
No. of patients
Gestational trophoblastic disease Trophoblastic cells Chorionic villi Normal endometrial tissue
6
Serum {3-hCG (mIV/ml) Mean
11,292
I
Range
1,220-16,362
6
4,716.5
259-15,947
3
2,396.7
140-4,500
9
7,019.3
14-20,900
tational choriocarcinoma not preceded by a hydatidiform mole. Interest in curettage for such patients waned during the next 7 years. Another 17 women underwent curettage during follow-up for hydatidiform mole in the 20-month period from November 1987 through June 1989. During these two time periods a repeat curettage was performed during the follow-up for hydatidiform mole if (1) R>-human chorionic gonadotropin serum (R>-hCG) levels plateaued or rose or (2) excessive uterine bleeding occurred. The clinical records were reviewed for initial management of the hydatidiform mole, the presence of bleeding, the size of the uterus, the trend of serum R>hCG levels before the curettage, the level of serum R>1465
1466 Schlaerth, Morrow, and Rodriguez
June 1990 Am J Obstet Gynecol
Table II. Uterine curettage performed for excessive bleeding from gestational trophoblastic disease Serum f3-hCG Patient
mIUlml
I
Pathologic histology
Trend curettage
Uterine size
Gm
18
P. C.
1080
Falling
Normalt
D.D.
6200
Falling
Large:j:
M.H.
1800
None*
L. M.
77800
A.P.
278
I
Days after mole-pregnancy
Tissue
Outcome
Atypical trophoblasts
32
Lost to follow-up
200
Decidua, blood
31
Large
30
Hydatidiform mole
16
Spontaneous remIssIon
None*
Large
230
Hydatidiform mole
7
Falling
Normal
3
Endometrium
31
Spontaneous remission Spontaneous remIssIon Chemother~p.y;
P. F.
Normal
None*
3880
9
Choriocarinoma
remIssIon Chemotherapy; hysterecto~~; remIssIon
197
Other
Blood transfusion
Lung metastasis Perforation
*Single value (?). t<8 Weeks' gestational size. :j:>8 Weeks' gestational size.
Table III. Uterine curettage performed in patients with metastatic trophoblastic disease Pathologic histology
Serum f3-hCG Patient
L. G. M. A. P. S. S. G.A. M.L.
J.
mIUlml
I
870 665 278 1070 86400 550
Trend at curettage
Uterine size
Gm
Plateau Plateau Declining Plateau None Plateau
Normal* Normal Normal Normal Larget Normal
Fragments 18 3 2 7 2
I
Tissue
Days after mole-pregnancy
Endometrium Endometrium Endometrium Hydatidiform mole Endometrium Decidua
48 40 31 59 79 41
*<8 Weeks' gestational size. t>8 Weeks' gestational size.
hCG at the curettage, and for evidence of metastasis. Further, the quantity of the curettage specimen and the histologic descriptions were analyzed. A uterus was considered enlarged if a sounding exceded 10 cm or the estimate of size was >8 weeks' gestational size. Persistent gestational trophoblastic disease was diagnosed by a rise or plateau in serum (3liCG levels or by the appearance of metastasis. A rising trend in serum (3-hCG levels was defined as doubling in value over a 2-week period. A plateau in hCG levels was generally considered to be present when no decrease in serum (3-hCG level was apparent during 3 weeks of observation and any increase was insufficient to qualify as a rising trend. Assessment for metastasis included history and physical examination, liver func-
tion tests, chest roentgenogram, pelvic ultrasonographic examination, and computerized tomography of the chest, abdomen, brain and pelvis. Earlier patients underwent radioisotope scans of the brain and liver and pelvic angiography. The uterine curettage specimen was considered positive if a histologic diagnosis of'a gestational trophoblastic disease or trophoblastic cells were detected, otherwise it was considered negative for diagnostic purposes. Last, the details in management and clinical outcome were determined for all patients. Results
General observations. The yield from the curettages were analyzed for the 24 women with non metastatic
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Table IV. Uterine curettage in patients with unsubstantiated trophoblastic disease in retrospect (immediate precurettage titer hCG showed decline*) Serum {3-hCG Patient
mIUlml
I
Pathologic histology
Trend at curettage
Uterine sIze
Tissue
Days after mole-pregnancy
5
Trophoblastic
45
Atypical trophoblastic Chorionic villi
32
Endometrium
49
I
Gm
E. C.
1400
Plateau
Larget
P. C.
1080
Plateau
Normal:j:
18
R. F.
133
Plateau
Normal
3
K. B.
1640
Rise
Normal
76
Outcome
Hysterectomy for performation. remission Lost to follow-up Spontaneous remission Spont~neous remiSSion
*Value not received until after curettage. t>8 Weeks' gestational size. :j:<8 Weeks' gestational size.
Table V. Uterine curettage followed by spontaneous remission of nonmetastatic trophoblastic disease Pathologic histology
Serum {3-hCG Patient
mIUlml
R. M.
643
B. C.
25200
V. M.
5430
R. D.
259
I
Trend at curettage
Uterine size
Gm
Rise
Normal*
Plateau
Larget
16
Rise
Normal
2
Plateau
Normal
8
I
Tissue
Days after mole-pregnancy
Trophoblasts
53
Hydatidiform mole Bizarre trophoblasts Trophoblasts
62 42 88
Outcome
Spontaneous in 20 days Spontaneous in 30 days Spontaneous in 42 days Spontaneous in II days
remission remission remission remission
*<8 Weeks' gestational size. t>8 Weeks' gestational size.
trophoblastic disease (Table I). Fifteen of 24 (62.5%) of those patients exhibited some aspect of trophoblastic histology. The uterine sizes were analyzed in reference to the diagnostic yield on the curettages. The curettings from eight of 12 (66.7%) large uteri contained trophoblastic elements. The curettings from 25 normal-sized uteri showed trophoblastic tissue in 13 (52%). Bleeding. Six patients underwent uterine curettage because of significant bleeding (Table II). Four of these women were clinically considered to have retention of molar tissue after evacuation. Two of these patients were evacuated at our institution. one (P. C.) by suction and sharp curettage to complete spontaneous abortion of the hydatidiform mole and the other (L. M.) underwent elective suction and sharp curettage for an intact hydatidiform mole. No details of primary management are known for the other two women (M. H., D. D.). One woman with metastatic postmolar trophoblastic disease and one woman with postabortal choriocarcinoma also underwent curettage. It should be noted
that this last patient sustained a uterine performation that led to laparotomy and hysterectomy. Persistent trophoblastic disease Metastatic. Six patients underwent uterine curettage as part of their assessment for metastatic trophoblastic disease (Table III). The preceding gestation in five patients was a hydatidiform mole and a tubal pregnancy in one (G. A.). One patient (A. P.) with metastasis was first seen with bleeding and is included under both groups of patients. N onrnetastatic. A total of 28 women underwent uterine curettage for presumed nonmetastatic postmolar trophoblastic disease on the basis of the trend of serum hCG levels. Two women with serum hCG trends suggesting postmolar trophoblastic disease also were first seen with bleeding and are included in Table II. :I'li . Despite a trend of serum l3-hCG levels to substantIate the diagnosis of non metastatic postmolar trophoblastic disease. four patients had a significant drop in l3-hCG level in the serum specimen drawn immediately before curettage (Table IV). Therefore. in retrospect the di-
1468 Schlaerth, Morrow, and Rodriguez
June 1990 Am J Obstet Gynecol
Table VI. Uterine curettage followed by a nonsustained fall in serum j3-hCG levels in patients wIth non metastatic trophoblastic disease Serum f3-hCG Patient
mIU I ml
I Trend at
Pathologic histology
curettage
Uterine size
I
Gm
S.W. T. C.
140 1170
Plateau Rise
Normal* Normal
M.M.
5340
Plateau
Larget
15
H. S.
16362
Rise
Large
225
T. D.
15700
Rise
Normal
3
S. J.
V. M. E. S.
3380 20900 2550 1270
Plateau Plateau Rise Plateau
Normal Normal Normal Normal
24 1 2 4
L.R.
15947
Plateau
Large
A.A.
5 3
Serum f3-hCG (mIUlml) Day after mole-pregnancy
Tissue
Chorionic villi Necrotic trophoblasts Hydatidiform mole Hydatidiform mole Hydatidiform mole Trophoblasts Endometrium Chorionic villi Hydatidiform mole Trophoblasts
730
At nadir
I
At start of treatment
I
Trend
32 29
18 273
37 648
Plateau Rise
29
520
645
Plateau
26
2130
7100
Rise
39
378
915
Rise
42 57 37 34
638 8933 2300 834
1190 11900 6900 930
Plateau Plateau Plateau Plateau
26
15100
16600
Plateau
*<8 Weeks' gestational size. t>8 Weeks' gestational size.
Table VII. Uterine curettage without effect in patients with nonmetastatic trophoblastic disease Serum f3-hCG Patient
mIUlml
I
Pathologic histology
Trend at curettage
Uterine Size
Gm
J.w.
14 6140
Plateau Plateau
Normal* Normal
3 2
B. A.
2920 5700 2640 4030
Rise Rise Plateau Rise
Normal Larget Large Normal
2 1 6 4
L. M.
T. M.
N.V. C.M.
I
Tissue
Endometrium Necrotic cellular debris Blood Blood Trophoblasts Endometrium
Serum f3-hCG (mIU Iml) Days after mole-pregnancy
At treatment
I
Trend
152 31
17 7300
Plateau Plateau
30 47 43 36
4310 16000 6820 13100
Plateau Rise Rise Rise
*<8 Weeks' gestational size. t>8 Weeks' gestational size. agnosis of postmolar trophoblastic disease at the curettage could not be sustained. The diagnostic and therapeutic effects of these curettages are also questionable. However, one patient (E. C.) did have an invasive mole. Another patient (P. C.) is also included among those curetted for bleeding in Table I. After curettage four patients went into complete remission without further treatment. There was no clinical suspicion noted that incomplete evacuation of the hydatidiform mole had occurred in these patients (Table V). Ten patients had a decline in serum j3-hCG values after curettage that was not sustained (Table VI). All these women subsequently had a serum j3-hCG trend again indicating postmolar trophoblastic disease. All were successfully treated to remission with chemotherapy. Six patients underwent curettage at the time of diagnosis of non metastatic gestational trophoblastic dis-
ease and showed no effect from this procedure on their disease as evidenced by a continuous plateau or rise in serum j3-hCG levels during a period of observation afterward (Table VII). All these women were treated to successful remission with chemotherapy. Four women with nonmetastatic trophoblastic disease had no postcurettage follow-up, which rendered them unevaluable for therapeutic effect from this procedure (Table VIII). One patient (P. F.) included here was also considered among the patients who were first seen with bleeding (Table II).
Comment The curettages done for bleeding were not elective procedures and, as mentioned previously, four of these clinical situations were considered incomplete molar evacuations. But the presence of bleeding, the declining trend in serum j3-hCG levels, molar tissue in 2/4 patients, and spontaneous remission after curettage fit
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Table VIII. Uterine curettage without follow-up in patients with nonmetastatic trophoblastic disease Serum {3-hCG
Pathologic histology
Trend at curettage
Uterine size
Gm
4500
Rise
Large
350
s.
4500
Plateau
Normal
T. G.
17800
Rise
P. F.
3880
None
Patient
mIUlml
A.G. M.
I
I
Tissue
Days after mole-pregnancy
36
2
Blood, endometrium Trophoblasts
Normal
0
Endometrium
27
Normal
9
Choriocarcinoma
Outcome
Chemotherapy, remission Chemotherapy, remission Perforation, laparotomy, lost to follow-up Perforation, hysterectomy, chem?t~erapy, remiSSion
28
197
Table IX. Therapeutic effect of curettage in nonmestatic trophoblastic disease Serum {3-hCG (mIUlml)
Remission with curettage No remission with curettage
No.
Mean
4
7883
16
6513
well with the concept of incomplete abortion as opposed to nonmetastatic postmolar trophoblastic disease. Two of these women had their initial evacuation at our institution. During the time periods of this study 140 patients received initial management of their molar pregnancy at Women's Hospital for a 2/140 (1.4%) incomplete evacuation rate. In this series 21 of37 women (56.8%) had curettages that revealed trophoblastic tissue. This experience is similar to the 46% and the 70% positive curettage rate reported in the two series by Berkowitz. 5 • 6 Only nine (24.3%) women had a sufficient curettage specimen to allow a histologic diagnosis (eight hydatidiform moles and one choriocarcinoma). Nine women (24.3%) had trophoblastic tissue that, although insufficient in amount for histologic diagnosis would still allow analysis for prognostic features such as those described by Hertig7 and Deligdisch. B Inasmuch as all patients who were not lost to follow-up in this series had remission of their disease with curettage, chemotherapy, hysterectomy, or a combination of these modalities, it is difficult to make a statement with regard to the importance of histologic diagnosis in clinical management. Berkowitz5 found that one course of chemotherapy with methotrexate and citrovorum factor was definitive therapy for 95% of trophoblastic disease patients who had no trophoblastic tissue in the curettage specimen, whereas 59% of women with trophoblastic tissue in their curettages required more than one course of ther-
-'
Positive curettage
Range
No.
259-25200
4/4
14-20900
9/16
I
% 100
56.25
apy for clinical remission. It has been the practice at our institution to treat such women with weekly or biweekly courses of chemotherapy until one course has been given after a normal serum ~-hCG level. This practice and the fact that several different chemotherapy regimens have been used in these women does not allow comparison on this point with the Berkowitz5 senes. With the use of a serum ~-hCG level of 50,000 mIU 1ml Berkowitz5 found a rough correlation with trophoblastic tissue in the curettage specimen and multiple courses of chemotherapy. However, in this present series (Table I) there was no apparent correlation between trophoblastic tissue in the curettings and serum ~-hCG levels in patients with nonmetastatic trophoblastic disease. Therefore as a predictor of response, serum ~-hCG levels seem more applicable clinically than diagnostic curettage results. In our small experience with uterine curettage in metastatic gestational trophoblastic disease no benefit of curettage on an elective basis could be shown. It is likely that the tradition for repeated curettages is based on older experiences with patients, such as those in Table V, in whom a convincing therapeutic effect was apparent after a plateau or rise in serum 13hCG levels. The analysis in this report did not disclose how these four patients differed from those patients whose nonmetastatic trophoblastic disease persisted after curettage (Table IX) other than that all their cu-
1470 Schlaerth, Morrow, and Rodriguez
rettages were positive for trophoblastic tissue versus a 9/16 (56.25%) positive rate for the others. It is probable that most or all their trophoblastic disease was located in the superficial myometrium and the endometrium, both within reach of the curette. 1 In this regard diagnostic imaging techniques could prove helpful in the selection of optimal candidates for therapeutic curettage. Berkowitz5 has reported that ultrasonography can be helpful in the prediction of a positive curettage 73.9% (17/23) of the time. The intriguing observation that curettage may be definitive therapy in 20% (4/20) of patients with nonmetastatic trophoblastic disease must be tempered by the fact that all three patients (8.1 %) who sustained a uterine perforation required laparotomy and two underwent hysterectomy. These three curettages were performed by third-year resident physicians with staff physicians in attendance. It is well documented that myometrial invasion, perforation, and hemoperitoneum can all occur spontaneously with trophoblastic tumors. This process renders elective curettage for postmolar gestational trophoblastic disease a procedure with some risk to fertility. This is of particular concern because most of these women are young with a current interest in having children. In view of these facts, unless a group to benefit therapeutically from curettage can be clearly identified, there does not appear to be a significant place for elective curettage in women with postmolar gestational trophoblastic disease. REFERENCES 1. Bagshawe KD. Surgery in the diagnosis and treatment of trophoblastic tumors. In: Choriocarcinoma. Baltimore: Williams and Wilkins, 1969:133-41. 2. Hilgers RD, Lewis]L. Gestational trophoblastic neoplasia. GynecolOncol 1974;2:460-75. 3. Hammond Cb, Weed] C, Currie]L. The role of operation in the current therapy of gestational trophoblastic disease. AM] OBSTET GYNECOL 1980;136:844-58. 4. Lao TTH, Lee FHC, Yeung SSL. Repeat curettage after evacuation of hydatidiform mole. Acta Obstet Gynecol Scand 1987;66:305-7. 5. Berkowitz RS, Desai U, Goldstein DP, Driscoll SG, Marean AR, Berstein MR. Pretreatment curettage-a predictor of chemotherapy response in gestational trophoblastic neoplasia. Gynecol Oncol 1980;10:39-43. 6. Berkowitz RS, Birnholz ], Goldstein DP, Bernstein MR. Pelvic ultrasonography and the management of gestational trophoblastic disease. Gynecol OncoI1983;15:403-12. 7. Hertig A], Sheldon WHo Hydatidiform mole: a pathologicoclinical correlation. AM] OBSTET GYNECOL 1974;53:124. 8. Deligdisch L. Driscoll SG, Goldstein DP. Gestational trophoblastic neoplasma: morphologic correlater of therapeutic response. AM] OBSTET GYNECOL 1978;130:801-6. Editors' note: This manuscript was revised after these discussions were presented.
June 1990 Am J Obstet Gynecol
Discussion
R. SMITH, Seattle, Washington. Drs. Schlaerth and Morrow have reviewed for us the Los Angeles County Hospital experience with pretreatment curettage in the management of gestational trophoblastic neoplasia over the past 13 years. The purpose of their review was to assess the value of this traditional modality. The data base consists of 37 patient records that detail curettage procedures in the course of gestational trophoblastic neoplasia evaluation. Six were done for bleeding, six for evaluation of metastatic disease, and 27 for assessment of nonmetastatic disease. Of the six done for bleeding, four were because of clinically obvious retained products after molar evacuation. In each case, bleeding was controlled and spontaneous remission ensued. In the fifth case, bleeding was controlled, but metastatic disease prompted chemotherapy. In the sixth case, uterine perforation prompted hysterectomy before chemotherapy. No benefit, therapeutic or prognostic, was achieved in the five instances in which curettage was performed as part of the workup of metastatic gestational trophoblastic neoplasia. Four of 27 who underwent curettage during evaluation of nonmetastatic gestational trophoblastic neoplasia required no further treatment. No therapeutic or prognostic benefit was noted in the remaining 23, and one required hysterectomy for uterine perforation. Nine of 37 (24.3%) benefitted either through control of bleeding or eradication of disease. Two of 37 (5.4%) required hysterectomy for control of bleeding associated with postcurettage uterine perforation. Twentysix of 37 (70.3%) derived no benefit whatsoever. All were ultimately cured of their disease. The authors conclude that there is no clear indication for uterine curettage in the management of postmolar gestational trophoblastic neoplasia, except in the bleeding patient with evidence of retained tumor. One must reconcile this advice with the recommendations of our colleagues in gynecologic pathology who, although not always in agreement with one another with regard to interpretation of an individual case, do find that the morphologic criteria found in the 60% or so of positive curettage specimens provide useful prognostic information. Similarly, one must reconcile this advice with the recommendations of experienced clinicians who find that debulking of nonmetastatic gestational trophoblastic neoplasia by curettage may eliminate the need for chemotherapy in some patients and reduce the total number of treatment courses in others. We are aided in our reconciliation by the abundance of data worldwide that show that the extraordinary specificity and sensitivity of the radioimmunoassay for the ~-hCG far exceeds that of microscopic histopathology, immunochemistry, and diagnostic imaging in establishing both the diagnosis of gestational trophoDR. MICHAEL
Volume 162 Number 6
blastic neoplasia and its response to treatment at no patient risk. It is similarly abundantly clear that the success of systemic chemotherapy guided by serial ~-hCG levels far exceeds that of surgical extirpation alone with comparable, or perhaps less, patient risk. Chemotherapy is clearly the gold standard, with surgery assuming an adjuvant role for resection of chemotherapy-resistent metastases or for elective hysterectomy in the patient with no interest in subsequent fertility. The day before I received this manuscript, as if on cue a young woman 5 months after evacuation of a mole was referred to me. She had undergone two postevacuation curettage procedures before referral because of plateauing and subsequent elevation of her ~-hCG titers even though her initial evacuation was thought to be complete and the first curettage was negative. She has since responded completely to three courses of methotrexate-two given while her titer was elevated and the final given after her titer returned to normal. In 1981, Drs. Schlaerth and Morrow l helped us better understand the ~-hCG regression curve, and today it is the role of uterine curettage in this disease. I look forward to their continued contribution to our understanding of this disease. I have but one question for Dr. Schlaerth. If confronted with heavy bleeding in a young patient with postmolar gestational trophoblastic neoplasia and a normal sonogram or magnetic resonance imaging (MRI), how would you proceed? REFERENCES I. Schlaerth SB, Morrow CP, Kletsky OA, et al. Prognostic characteristic of the serum radioimmunoassay beta subunit human chorionic gonadotropin titer regression curve following molar pregnancy. Obstet Gynecol 1981 ;58:478.
Curettage in gestational trophoblastic disease
1471
DR. HISHAM K. TAMIMI, Seattle, Washington. We have used intraoperative ultrasonography after the evacuation of 20 molar pregnancies in the past 5 years. The only patient who required chemotherapy was one with lung metastasis. I welcome your comments about the potential for this technique to minimize the need of repeat curettage and even to reduce the need for chemotherapy. DR. JOSEPH OLIVER, Pasadena, California. When do you allow these patients to become pregnant again? Did amenorrhea or Asherman's syndrome develop in any of your patients because of curettage? DR. SCHLAERTH (Closing). Dr. Smith asked what I would do about a patient with heavy bleeding from postmolar gestational trophoblastic disease if she had a sonogram and MRI that revealed nothing suspicious. In one such patient, we did a curettage and the sonogram turned out to be a false-negative one, as it is in this setting from time to time. I have little information about the MRI in this setting. It takes a rather long time to do an MRI, and heavy bleeding may not allow that. The bottom line here is that the clinical situation would dictate what I would do. With heavy bleeding, my first response would be curettage. Dr. Tamimi, your question about intraoperative ultrasonography is part of a larger question of the role played by imaging and endoscopy in the identification of patients who might be cured with curettage alone. We continue to search for solutions to the dilemmas our study has shown and imaging techniques may be the answer. Dr. Oliver, by and large, for patients with non metastatic disease, we ask for a I-year interval before they become pregnant again. I am not aware of any of our patients in whom Asherman's syndrome developed subsequent to curettage. However, our long-term follow-up, as I am sure you realize, is poor.