Women with raised but falling human chorionic gonadotropin concentrations 6 months after a molar pregnancy do not need chemotherapy, as almost all of them will spontaneously remit, the results of a large retrospective cohort study have shown.
The findings, published online Nov. 28 in the Lancet (doi:10.1016/S0140-6736[11]61265-8), challenge current international clinical guidelines (Int. J. Gynecol. Obstet. 2002;77:285-7) that consider chemotherapy to be indicated when hCG concentrations are high for 6 months or more following evacuation of a hydatidiform mole.
The new findings argue that an elevated hCG level at 6 months is not an indicator of malignancy when values are falling, and that instead of initiating chemotherapy, women with raised but falling hCG can undergo surveillance of their hCG levels, with testing until they return to normal. Chemotherapy is needed only if hCG levels are still rising at 6 months, have plateaued, or are greater than 345 IU/L, or if there is radiologic evidence of neoplasia.
If the surveillance approach were to become standard, more women could avoid exposure to toxic chemotherapy drugs and could safely conceive sooner after evacuation of a molar pregnancy, said the authors of the study led by Dr. Roshan Agarwal of Imperial College London. Current U.K. guidelines advise women not to become pregnant until 12 months following chemotherapy, whereas they would have to wait only 6 months after a spontaneous return to normal hCG.
For their research, Dr. Agarwal and colleagues retrospectively identified 13,960 women registered at London’s Charing Cross Hospital between January 1993 and May 2008 who had undergone evacuation of a complete or partial hydatidiform mole. Of these, 974 (7%) required chemotherapy within 6 months, and hCG normalized spontaneously in 12,910 (92%) within 6 months.
The remaining 76 women still had high hCG concentrations (more than 5 IU/L) 6 months after evacuation of the molar pregnancy. Sixty-six patients underwent surveillance, in which blood and urine samples were collected and evaluated every 2 weeks until normal hCG was achieved, followed by monthly urine samples for 6 months. Ten patients underwent chemotherapy.
In the surveillance group, 98% of patients (n = 65) saw hCG values return to normal without chemotherapy (in all but 6 of them within a year), and the remaining patient, who had chronic renal failure, remained healthy despite having elevated hCG, Dr. Agarwal and colleagues reported.
Among the 10 patients who received chemotherapy, 6 had complete responses, and 4 had partial or no responses but remained well, even though hCG concentrations in 2 patients continued to be elevated. There was no significant difference in time to normalization between the groups and no deaths had occurred in either group after a median 2 years’ follow-up.
The investigators acknowledged as a weakness of their study its retrospective design, the use of a single study site, and the small number of patients with raised hCG at 6 months. However, they said, the findings "directly challenge the present clinical dogma" to show that the surveillance model is clinically acceptable. The results "will change international practice and spare women unnecessary exposure to chemotherapy," they wrote in their analysis.
In a case study linked to Dr. Agarwal and colleagues’ article, Rosemary A. Fisher, also of Imperial College London, described a woman who had a miscarriage and three consecutive molar pregnancies, yet was able to achieve a normal pregnancy with use of a donor egg.
"To the best of our knowledge, this report establishes for the first time that oocyte donation can enable women with familial recurrent hydatidiform moles due to NLRP7 mutations to achieve a normal pregnancy," Ms. Fisher and colleagues wrote, adding that this finding offered "hope to other women with this condition." The study also shows "that the major role of NLRP7 in pregnancy is in the developing oocyte."
The study was funded by the National Commissioning Group, the Imperial Experimental Cancer Medicine Center, the Imperial Biomedical Research Center, and Cancer Research UK. The authors of the cohort study and case report declared that they had no relevant financial disclosures.