November 30, 2011 — Surveillance instead of chemotherapy might be sufficient for women after a molar pregnancy, and would prevent unnecessary exposure to the toxic effects of agents such as methotrexate. According to a study published online November 29 in the Lancet, high levels of human chorionic gonadotropin (hCG) will spontaneously decline in most cases, negating the need to actively intervene with chemotherapeutic agents.
"Chemotherapy should only be considered in patients whose hCG concentrations are greater than 345 IU/L, and when radiological evidence of disease is present or when hCG levels are consistently plateaued or rising," write the authors, led by Michael J. Seckl, MBBS, PhD, FRCP, from the Department of Medical Oncology, Charing Cross Hospital Campus, London, United Kingdom.
A hydatidiform mole, or molar pregnancy, is an abnormal form of pregnancy in which a nonviable fertilized egg implants in the uterus. Partial and complete hydatidiform moles overexpress paternal genes, the authors note. Complete moles are diploid and androgenetic in origin, and partial moles are triploid and have 1 maternal set and 2 paternal sets of chromosomes.
Molar pregnancies are more common in east Asia than in most western regions. In the United Kingdom, it is estimated that 1 to 3 per 1000 pregnancies are either complete or partial moles.
In all cases, serum or urine hCG concentrations are elevated (5 IU/L or more on the Charing Cross hCG assay). Residual tissue regression occurs spontaneously in most patients, and a corresponding normalization of hCG concentrations is observed in about 92% of patients. However, in a minority of women, progression to malignancy occurs. Progression to gestational trophoblastic neoplasia occurs in about 15% of cases after a complete hydatidiform mole and in about 0.5% to 1.0% of cases after a partial hydatidiform mole.
In the United Kingdom, approximately 8% of patients with hydatidiform moles undergo chemotherapy, generally with methotrexate or dactinomycin monotherapy. Current indications for chemotherapy in gestational trophoblastic disease include elevated hCG concentrations 6 months after uterine evacuation of the hydatidiform mole, even when levels are declining.
No Significant Difference Seen
Dr. Seckl and colleagues sought to establish whether chemotherapy is always necessary in this population.
They retrospectively identified 13,960 women who were registered at Charing Cross Hospital from January 1993 too May 2008 and who had persistently high hCG concentrations 6 months after the evacuation of a hydatidiform mole. The authors examined the rates of normalization of hCG concentration, relapse, and death in patients who were under surveillance and in those who received chemotherapy.
Dr. Seckl and his team hypothesized that a surveillance policy would be clinically acceptable if hCG values returned to normal in 75% of patients or more within 12 months of evacuation and if less than 25% of them developed gestational trophoblastic neoplasia and required chemotherapy.
In the study cohort, 974 patients (7%) required chemotherapy and 12,910 (92%) had their hCG return to normal levels spontaneously within 6 months of evacuation; the remaining 76 (<1%) had high hCG levels that persisted 6 months after evacuation.
Of these 76 remaining patients, 46 (61%) had complete moles, 25 (33%) had partial moles, and 5 (7%) were unclassified. At registration, median plasma hCG concentration was 1343.5 IU/L, peak hCG was 1386 IU/L, hCG at 6 months was 13.5 IU/L, and time to hCG normalization was 7.5 months. The authors note that, overall, hCG concentration at 6 months modestly correlated with time to normalization.
The majority of the patients (n = 66; 87%) continued under surveillance. In all except 1 patient, hCG values spontaneously returned to normal without chemotherapy. The levels in that patient did not normalize because of chronic renal failure.
Of the 10 patients who received chemotherapy, hCG concentrations returned to normal in 8 (80%). In 2 of these patients, values remained slightly high (6 to 11 IU/L), although they had no associated clinical problems once they finished treatment.
There were no significant differences in the return of hCG concentrations between the surveillance and chemotherapy groups (P = .044). The only difference seen was lower median hCG concentrations 6 months after evacuation in surveillance group.
The authors acknowledge that the study is limited by small patient numbers and retrospective data, and that a "further prospective study in a multicenter setting would be useful."
In the absence of these data, they write, "we recommend that women with persistently high hCG concentrations 6 months after evacuation should continue regular hCG monitoring rather than begin chemotherapy."
The study was funded by National Commissioning Group, the Imperial Experimental Cancer Medicine Centre, the Imperial Biomedical Research Centre, and Cancer Research UK. The authors have disclosed no relevant financial relationships.
Lancet. Published online November 29, 2011. Abstract
"Chemotherapy should only be considered in patients whose hCG concentrations are greater than 345 IU/L, and when radiological evidence of disease is present or when hCG levels are consistently plateaued or rising," write the authors, led by Michael J. Seckl, MBBS, PhD, FRCP, from the Department of Medical Oncology, Charing Cross Hospital Campus, London, United Kingdom.
A hydatidiform mole, or molar pregnancy, is an abnormal form of pregnancy in which a nonviable fertilized egg implants in the uterus. Partial and complete hydatidiform moles overexpress paternal genes, the authors note. Complete moles are diploid and androgenetic in origin, and partial moles are triploid and have 1 maternal set and 2 paternal sets of chromosomes.
Molar pregnancies are more common in east Asia than in most western regions. In the United Kingdom, it is estimated that 1 to 3 per 1000 pregnancies are either complete or partial moles.
In all cases, serum or urine hCG concentrations are elevated (5 IU/L or more on the Charing Cross hCG assay). Residual tissue regression occurs spontaneously in most patients, and a corresponding normalization of hCG concentrations is observed in about 92% of patients. However, in a minority of women, progression to malignancy occurs. Progression to gestational trophoblastic neoplasia occurs in about 15% of cases after a complete hydatidiform mole and in about 0.5% to 1.0% of cases after a partial hydatidiform mole.
In the United Kingdom, approximately 8% of patients with hydatidiform moles undergo chemotherapy, generally with methotrexate or dactinomycin monotherapy. Current indications for chemotherapy in gestational trophoblastic disease include elevated hCG concentrations 6 months after uterine evacuation of the hydatidiform mole, even when levels are declining.
No Significant Difference Seen
Dr. Seckl and colleagues sought to establish whether chemotherapy is always necessary in this population.
They retrospectively identified 13,960 women who were registered at Charing Cross Hospital from January 1993 too May 2008 and who had persistently high hCG concentrations 6 months after the evacuation of a hydatidiform mole. The authors examined the rates of normalization of hCG concentration, relapse, and death in patients who were under surveillance and in those who received chemotherapy.
Dr. Seckl and his team hypothesized that a surveillance policy would be clinically acceptable if hCG values returned to normal in 75% of patients or more within 12 months of evacuation and if less than 25% of them developed gestational trophoblastic neoplasia and required chemotherapy.
In the study cohort, 974 patients (7%) required chemotherapy and 12,910 (92%) had their hCG return to normal levels spontaneously within 6 months of evacuation; the remaining 76 (<1%) had high hCG levels that persisted 6 months after evacuation.
Of these 76 remaining patients, 46 (61%) had complete moles, 25 (33%) had partial moles, and 5 (7%) were unclassified. At registration, median plasma hCG concentration was 1343.5 IU/L, peak hCG was 1386 IU/L, hCG at 6 months was 13.5 IU/L, and time to hCG normalization was 7.5 months. The authors note that, overall, hCG concentration at 6 months modestly correlated with time to normalization.
The majority of the patients (n = 66; 87%) continued under surveillance. In all except 1 patient, hCG values spontaneously returned to normal without chemotherapy. The levels in that patient did not normalize because of chronic renal failure.
Of the 10 patients who received chemotherapy, hCG concentrations returned to normal in 8 (80%). In 2 of these patients, values remained slightly high (6 to 11 IU/L), although they had no associated clinical problems once they finished treatment.
There were no significant differences in the return of hCG concentrations between the surveillance and chemotherapy groups (P = .044). The only difference seen was lower median hCG concentrations 6 months after evacuation in surveillance group.
The authors acknowledge that the study is limited by small patient numbers and retrospective data, and that a "further prospective study in a multicenter setting would be useful."
In the absence of these data, they write, "we recommend that women with persistently high hCG concentrations 6 months after evacuation should continue regular hCG monitoring rather than begin chemotherapy."
The study was funded by National Commissioning Group, the Imperial Experimental Cancer Medicine Centre, the Imperial Biomedical Research Centre, and Cancer Research UK. The authors have disclosed no relevant financial relationships.
Lancet. Published online November 29, 2011. Abstract
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