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Duration of human chorionic gonadotropin surveillance for partial hydatidiform moles
American Journal of Obstetrics and Gynecology (2005) 192, 1362–4
www.ajog.org
RESIDENTS’ PAPERS GYNECOLOGY
Duration of human chorionic gonadotropin surveillance for partial hydatidiform moles Isaac Lavie, MD,a Gautam G. Rao, MD,b Diego H. Castrillon, MD, PhD,c David S. Miller, MD,b John O. Schorge, MDb,* Department of Obstetrics and Gynecology,a Division of Gynecologic Oncology,b Southwestern Trophoblastic Disease Center, and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texc Received for publication August 25, 2004; revised December 16, 2004; accepted December 20, 2004
KEY WORDS Human chorionic gonadotropin Molar pregnancy
Objective: Partial hydatidiform moles infrequently progress to gestational trophoblastic neoplasia. The purpose of this study was to determine the optimal duration of human chorionic gonadotropin surveillance. Study design: We retrospectively reviewed the clinical follow-up of all women who were diagnosed with partial hydatidiform mole at our institution from 1983 to 2003. Results: One hundred sixty-three patients were identified with a median age of 23 years (range, 14-42 years). Seventy-four patients (45%) attained undetectable levels of human chorionic gonadotropin; none of the patients had gestational trophoblastic neoplasia. Forty patients completed the 6 months of recommended follow-up; 6 patients conceived during surveillance, and 28 patients did not return for any further office visits 1 to 5 months after achieving remission. Eighty-three patients (51%) were lost to follow-up before normalization of human chorionic gonadotropin. Six women (4%) had stage I gestational trophoblastic neoplasia during surveillance. Conclusion: Our results support the suggestion that a single undetectable human chorionic gonadotropin level after evacuation is sufficient follow-up to ensure remission in patients with partial hydatidiform moles. Ó 2005 Elsevier Inc. All rights reserved.
Serum human chorionic gonadotropin (hCG) is a sensitive indicator of persistent disease after the evacuation of a molar pregnancy. This marker can be
* Reprint requests: John O. Schorge, MD, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, J7.124, Dallas, TX 75390-9032. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.12.080
used effectively to diagnose postmolar gestational trophoblastic neoplasia (GTN), assess treatment response, and detect recurrent disease. After evacuation, hCG levels are monitored at least biweekly until they are undetectable. The American College of Obstetricians and Gynecologists currently recommends hCG followup evaluations at monthly intervals for 6 months thereafter.1 Indigent patients are poorly compliant with postmolar follow-up evaluations.2,3 We observed that only 34%
Lavie et al of women at Parkland Memorial Hospital who did not have GTN were fully compliant with surveillance. Fifteen percent of these patients never returned for a single office visit after evacuation.2 Massad et al3 reported that 18% of patients were fully compliant at Cook County Hospital in metropolitan Chicago. Poverty and patient apathy pose many potential obstacles to follow-up evaluation.4 A shorter postevacuation follow-up period is 1 option that would focus limited public health system resources without compromising patient care. Feltmate et al5 reviewed hCG serum titers after molar evacuation in patients who are diagnosed with complete mole, with the database from the New England Trophoblastic Disease Center. None of the 1029 patients who received this diagnosis between 1973 and 2001 had GTN after normalization of hCG. They concluded that patients who achieved undetectable serum hCG levels of !5 mIU/mL may be considered to be in remission and excused from further follow-up visits. Women with partial hydatidiform moles have GTN in only 5% of cases, compared with approximately 20% of complete hydatidiform moles.6 The purpose of this study was to determine the optimal duration of hCG surveillance.
Material and methods Institutional Review Board approval was obtained to retrospectively identify all women who were diagnosed with partial hydatidiform mole from 1983 to 2003 with the hospital tumor registry and Society of Gynecologic Oncology Database. The Parkland Health and Hospital System provides care for the uninsured and underinsured inner-city population of Dallas County and serves as the main teaching facility of the University of Texas Southwestern Medical School. Partial moles were diagnosed histopathologically. DNA ploidy analysis was incorporated routinely since becoming available at our institution in 1999. Women who received a diagnosis of molar pregnancy were referred to the gynecologic oncology clinic for follow-up. At the initial visit, patients were encouraged to begin hormonal contraception and return biweekly for hCG measurements (Bayer Centaur Immunoassay, Diamond Diagnostics, Holliston, Mass). Three biweekly hCG measurements !5 mIU/mL were required to confirm remission. Thereafter, the recommended postmolar surveillance included monthly hCG levels for a total of 6 months. Patients with a !10% decrease of hCG over 3 consecutive titers were considered to have plateaued and were diagnosed with GTN. Frequent attempts were made to contact patients by telephone, particularly if they failed to keep appointments. When patients could not be reached, certified letters that described the malignant potential of molar pregnancy and the importance of follow-up were sent to the last known address.2
1363 Table Compliance with recommended surveillance after evacuation for partial mole Compliance
N (n = 163)
Achieved remission without chemotherapy Fully compliant for 6 mo after remission Missed at least 1 visit Lost !6 mo after remission Conceived during surveillance* Conceived before remission Lost to follow-up without achieving remission Had GTN during surveillance
74 (45%) 34 6 28 6 0 83 (51%) 6 (4%)
* Remission confirmed after delivery.
Medical records were reviewed for demographics, clinical outcome, and follow-up. Chi-squared test and independent samples t test were performed with SPSS software (version 12.0; SPSS, Inc, Chicago, Ill). The level of significance was set at .05.
Results One hundred sixty-three patients received a diagnosis of partial hydatidiform mole during the study interval. The median age was 23 years (range, 14-42 years). One hundred thirty-five women (83%) were Hispanic; 15 women (9%) were black; 10 women (6%) were white, and 3 women (2%) were Asian. The median estimated gestational age at evacuation was 13 weeks (range, 5-30 weeks). Mean pre-evacuation hCG level was 210,682 mIU/mL (range, 356-2,023,000 m IU/mL). Seventy-four of 163 patients (45%) attained undetectable hCG levels (Table). These women subsequently had an additional 278 office visits (mean, 3.8 office visits) where hCG levels were !5 mIU/mL. None of the women had GTN. Forty women completed the 6 months of recommended follow-up visits; 6 women conceived during surveillance, and 28 women did not return for further office visits 1 to 5 months after achieving remission. Eighty-three patients (51%) were lost to follow-up before normalization of hCG. Six women(4%) were diagnosed with GTN on the basis of plateauing or rising hCG levels. None of the women achieved undetectable levels of hCG before diagnosis of GTN. The mean pre-evacuation hCG level was significantly higher in the group that subsequently had GTN (690,953 vs 174,500 mIU/mL; P ! .001). All were stage I low-risk (World Health Organization score, 0-6) and resolved with chemotherapy.
Comment Our results support the suggestion that a single undetectable hCG level after evacuation is sufficient follow-up to ensure remission in patients with partial
1364 hydatidiform moles. None of the 74 women in our study who achieved hCG normalization subsequently had GTN. At the New England Trophoblastic Disease Center, Feltmate et al7 reached the same conclusion after observing no relapses among 107 patients with partial mole who had at least 1 undetectable hCG level. Batorfi et al8 reported that none of 120 molar patients who were treated at the National Health Center in Hungary experienced relapse after achieving normalization of hCG levels. Trophoblastic disease centers that serve indigent women should explore the feasibility of simplified surveillance strategies. Excusing patients from further follow-up evaluation after they have achieved 1 hCG level !5 mIU/mL may result in cost savings without compromising care. This strategy would have prevented 278 serum hCG office visits to our public hospital system. Noncompliance with postmolar pregnancy surveillance is particularly problematic among the indigent population.2,3 Fifty-one percent of our partial mole patients were lost to follow-up without achieving remission. A shorter follow-up period would not appear to impact patient health or safety negatively and certainly would improve compliance.7 Resources would be best directed at encouraging follow-up until the normalization of hCG levels.
Lavie et al
References 1. American College of Obstetricians and Gynecologists. Diagnosis and treatment of gestational trophoblastic disease: ACOG practice bulletin no.: 53. Obstet Gynecol 2004;103:1365-77. 2. Allen JE, King MR, Farrar DF, Miller DS, Schorge JO. Postmolar surveillance at a trophoblastic disease center that serves indigent women. Am J Obstet Gynecol 2003;188:1151-3. 3. Massad LS, Abu-Rastam NR, Lee SS, Renta V. Poor compliance with postmolar surveillance and treatment protocols by indigent women. Obstet Gynecol 2000;96:940-4. 4. Jones ME, Cason CL, Bond ML. Access to preventative health care: Is method of payment a barrier for immigrant Hispanic women? Women Health Issues 2002;12:129-37. 5. Wolfberg AJ, Feltmate C, Goldstein DP, Berkowitz RS, Lieberman E. Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy. Obstet Gynecol 2004; 104:551-4. 6. Soper JT, Lewis JL, Hammond CB. Gestational trophoblastic disease. In: Hoskins WJ, Perez CA, Young RC, editors. Principles and practice of gynecologic oncology. 2nd ed., Philadelphia: Lippincott-Raven; 1997. p. 1039-77. 7. Feltmate CM, Batorfi J, Fulop V, Goldstein DP, Doszpod J, Berkowitz RS. Human chorionic gonadotropin follow-up in patients with molar pregnancy: a time for reevaluation. Obstet Gynecol 2003;101:732-6. 8. Batorfi J, Vegh G, Szepesi J, Szigetvari I, Doszpod J, Fulop V. How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data. Eur J Obstet Gynecol Reprod Biol 2004;112:95-7.
www.ajog.org
RESIDENTS’ PAPERS GYNECOLOGY
Duration of human chorionic gonadotropin surveillance for partial hydatidiform moles Isaac Lavie, MD,a Gautam G. Rao, MD,b Diego H. Castrillon, MD, PhD,c David S. Miller, MD,b John O. Schorge, MDb,* Department of Obstetrics and Gynecology,a Division of Gynecologic Oncology,b Southwestern Trophoblastic Disease Center, and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texc Received for publication August 25, 2004; revised December 16, 2004; accepted December 20, 2004
KEY WORDS Human chorionic gonadotropin Molar pregnancy
Objective: Partial hydatidiform moles infrequently progress to gestational trophoblastic neoplasia. The purpose of this study was to determine the optimal duration of human chorionic gonadotropin surveillance. Study design: We retrospectively reviewed the clinical follow-up of all women who were diagnosed with partial hydatidiform mole at our institution from 1983 to 2003. Results: One hundred sixty-three patients were identified with a median age of 23 years (range, 14-42 years). Seventy-four patients (45%) attained undetectable levels of human chorionic gonadotropin; none of the patients had gestational trophoblastic neoplasia. Forty patients completed the 6 months of recommended follow-up; 6 patients conceived during surveillance, and 28 patients did not return for any further office visits 1 to 5 months after achieving remission. Eighty-three patients (51%) were lost to follow-up before normalization of human chorionic gonadotropin. Six women (4%) had stage I gestational trophoblastic neoplasia during surveillance. Conclusion: Our results support the suggestion that a single undetectable human chorionic gonadotropin level after evacuation is sufficient follow-up to ensure remission in patients with partial hydatidiform moles. Ó 2005 Elsevier Inc. All rights reserved.
Serum human chorionic gonadotropin (hCG) is a sensitive indicator of persistent disease after the evacuation of a molar pregnancy. This marker can be
* Reprint requests: John O. Schorge, MD, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, J7.124, Dallas, TX 75390-9032. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.12.080
used effectively to diagnose postmolar gestational trophoblastic neoplasia (GTN), assess treatment response, and detect recurrent disease. After evacuation, hCG levels are monitored at least biweekly until they are undetectable. The American College of Obstetricians and Gynecologists currently recommends hCG followup evaluations at monthly intervals for 6 months thereafter.1 Indigent patients are poorly compliant with postmolar follow-up evaluations.2,3 We observed that only 34%
Lavie et al of women at Parkland Memorial Hospital who did not have GTN were fully compliant with surveillance. Fifteen percent of these patients never returned for a single office visit after evacuation.2 Massad et al3 reported that 18% of patients were fully compliant at Cook County Hospital in metropolitan Chicago. Poverty and patient apathy pose many potential obstacles to follow-up evaluation.4 A shorter postevacuation follow-up period is 1 option that would focus limited public health system resources without compromising patient care. Feltmate et al5 reviewed hCG serum titers after molar evacuation in patients who are diagnosed with complete mole, with the database from the New England Trophoblastic Disease Center. None of the 1029 patients who received this diagnosis between 1973 and 2001 had GTN after normalization of hCG. They concluded that patients who achieved undetectable serum hCG levels of !5 mIU/mL may be considered to be in remission and excused from further follow-up visits. Women with partial hydatidiform moles have GTN in only 5% of cases, compared with approximately 20% of complete hydatidiform moles.6 The purpose of this study was to determine the optimal duration of hCG surveillance.
Material and methods Institutional Review Board approval was obtained to retrospectively identify all women who were diagnosed with partial hydatidiform mole from 1983 to 2003 with the hospital tumor registry and Society of Gynecologic Oncology Database. The Parkland Health and Hospital System provides care for the uninsured and underinsured inner-city population of Dallas County and serves as the main teaching facility of the University of Texas Southwestern Medical School. Partial moles were diagnosed histopathologically. DNA ploidy analysis was incorporated routinely since becoming available at our institution in 1999. Women who received a diagnosis of molar pregnancy were referred to the gynecologic oncology clinic for follow-up. At the initial visit, patients were encouraged to begin hormonal contraception and return biweekly for hCG measurements (Bayer Centaur Immunoassay, Diamond Diagnostics, Holliston, Mass). Three biweekly hCG measurements !5 mIU/mL were required to confirm remission. Thereafter, the recommended postmolar surveillance included monthly hCG levels for a total of 6 months. Patients with a !10% decrease of hCG over 3 consecutive titers were considered to have plateaued and were diagnosed with GTN. Frequent attempts were made to contact patients by telephone, particularly if they failed to keep appointments. When patients could not be reached, certified letters that described the malignant potential of molar pregnancy and the importance of follow-up were sent to the last known address.2
1363 Table Compliance with recommended surveillance after evacuation for partial mole Compliance
N (n = 163)
Achieved remission without chemotherapy Fully compliant for 6 mo after remission Missed at least 1 visit Lost !6 mo after remission Conceived during surveillance* Conceived before remission Lost to follow-up without achieving remission Had GTN during surveillance
74 (45%) 34 6 28 6 0 83 (51%) 6 (4%)
* Remission confirmed after delivery.
Medical records were reviewed for demographics, clinical outcome, and follow-up. Chi-squared test and independent samples t test were performed with SPSS software (version 12.0; SPSS, Inc, Chicago, Ill). The level of significance was set at .05.
Results One hundred sixty-three patients received a diagnosis of partial hydatidiform mole during the study interval. The median age was 23 years (range, 14-42 years). One hundred thirty-five women (83%) were Hispanic; 15 women (9%) were black; 10 women (6%) were white, and 3 women (2%) were Asian. The median estimated gestational age at evacuation was 13 weeks (range, 5-30 weeks). Mean pre-evacuation hCG level was 210,682 mIU/mL (range, 356-2,023,000 m IU/mL). Seventy-four of 163 patients (45%) attained undetectable hCG levels (Table). These women subsequently had an additional 278 office visits (mean, 3.8 office visits) where hCG levels were !5 mIU/mL. None of the women had GTN. Forty women completed the 6 months of recommended follow-up visits; 6 women conceived during surveillance, and 28 women did not return for further office visits 1 to 5 months after achieving remission. Eighty-three patients (51%) were lost to follow-up before normalization of hCG. Six women(4%) were diagnosed with GTN on the basis of plateauing or rising hCG levels. None of the women achieved undetectable levels of hCG before diagnosis of GTN. The mean pre-evacuation hCG level was significantly higher in the group that subsequently had GTN (690,953 vs 174,500 mIU/mL; P ! .001). All were stage I low-risk (World Health Organization score, 0-6) and resolved with chemotherapy.
Comment Our results support the suggestion that a single undetectable hCG level after evacuation is sufficient follow-up to ensure remission in patients with partial
1364 hydatidiform moles. None of the 74 women in our study who achieved hCG normalization subsequently had GTN. At the New England Trophoblastic Disease Center, Feltmate et al7 reached the same conclusion after observing no relapses among 107 patients with partial mole who had at least 1 undetectable hCG level. Batorfi et al8 reported that none of 120 molar patients who were treated at the National Health Center in Hungary experienced relapse after achieving normalization of hCG levels. Trophoblastic disease centers that serve indigent women should explore the feasibility of simplified surveillance strategies. Excusing patients from further follow-up evaluation after they have achieved 1 hCG level !5 mIU/mL may result in cost savings without compromising care. This strategy would have prevented 278 serum hCG office visits to our public hospital system. Noncompliance with postmolar pregnancy surveillance is particularly problematic among the indigent population.2,3 Fifty-one percent of our partial mole patients were lost to follow-up without achieving remission. A shorter follow-up period would not appear to impact patient health or safety negatively and certainly would improve compliance.7 Resources would be best directed at encouraging follow-up until the normalization of hCG levels.
Lavie et al
References 1. American College of Obstetricians and Gynecologists. Diagnosis and treatment of gestational trophoblastic disease: ACOG practice bulletin no.: 53. Obstet Gynecol 2004;103:1365-77. 2. Allen JE, King MR, Farrar DF, Miller DS, Schorge JO. Postmolar surveillance at a trophoblastic disease center that serves indigent women. Am J Obstet Gynecol 2003;188:1151-3. 3. Massad LS, Abu-Rastam NR, Lee SS, Renta V. Poor compliance with postmolar surveillance and treatment protocols by indigent women. Obstet Gynecol 2000;96:940-4. 4. Jones ME, Cason CL, Bond ML. Access to preventative health care: Is method of payment a barrier for immigrant Hispanic women? Women Health Issues 2002;12:129-37. 5. Wolfberg AJ, Feltmate C, Goldstein DP, Berkowitz RS, Lieberman E. Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy. Obstet Gynecol 2004; 104:551-4. 6. Soper JT, Lewis JL, Hammond CB. Gestational trophoblastic disease. In: Hoskins WJ, Perez CA, Young RC, editors. Principles and practice of gynecologic oncology. 2nd ed., Philadelphia: Lippincott-Raven; 1997. p. 1039-77. 7. Feltmate CM, Batorfi J, Fulop V, Goldstein DP, Doszpod J, Berkowitz RS. Human chorionic gonadotropin follow-up in patients with molar pregnancy: a time for reevaluation. Obstet Gynecol 2003;101:732-6. 8. Batorfi J, Vegh G, Szepesi J, Szigetvari I, Doszpod J, Fulop V. How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data. Eur J Obstet Gynecol Reprod Biol 2004;112:95-7.