Likelihood Of Placental-Site Trophoblastic Tumors Linked To The Amount Of Time Since Related Pregnancy

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Main Category: Women's Health / Gynecology
Also Included In: Pregnancy / Obstetrics;  Cancer / Oncology
Article Date: 24 Jun 2009 - 7:00 PDT

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An article published Online First and in a future edition of The Lancet discusses the management of a rare condition called placental-site trophoblastic tumors (PSTTs). They are malignant tumors usually presenting months to years after pregnancy. The chances of surviving those tumors are linked to how much time elapsed since the related pregnancy took place. The article is written by Dr Peter Schmid and Professor Michael J Seckl, of the Imperial College NHS Healthcare Trust, London, UK, and colleagues. This paper is a milestone and the first study in thirty years to inform on a complete national experience of the disease. It represents the world's largest series.

After months or possibly years of a normal pregnancy, abortion, miscarriage, or hydatidiform mole, PSTTs can appear. They are slow-growing tumors. Molar pregnancy is an abnormal form of pregnancy, characterized by the presence of a hydatidiform mole (or hydatid mole, mola hytadidosa). Molar pregnancy comprises two distinct entities, partial and complete moles. Complete moles have no identifiable embryonic or fetal tissues and arise when an empty egg with no nucleus is fertilized by a normal sperm. In contrast, a partial mole occurs when a normal egg is fertilized by two spermatozoa. They are the rarest form of gestational trophoblastic disease (GTD) accounting for only 0.2 percent of all GTDs.

Trophoblasts are cells which provide nutrients to the embryo and develop into a large part of the placenta. They are formed during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg. From 2003 to 2007 one woman in 20,000 was diagnosed with PTTs in the UK. In this study, the researchers evaluated 35,550 women with GTD in the UK from 1976 to 2006. Out of these women, 62 were diagnosed with PSTT. Patients were treated with surgery, chemotherapy, or both. Then the probabilities were evaluated: overall survival and survival without recurrence of disease five and ten years after the date of first treatment. The authors looked at the association of these endpoints with various prognostic factors.

The study showed that probability of overall survival was 70 percent and probability of recurrence-free survival ten years after first treatment was 73 percent. Patients with stage I disease had a ten year probability of overall survival of 90 percent. They did not benefit from post-operative chemotherapy. Patients with stage II, III or IV disease needed both surgery and chemotherapy, or both. After ten years, overall survival was 52 percent for patients with stage II disease and 49 percent for those with stage III or IV disease. Patients with recurrent disease or disease resistant to treatment had poor survival, with only 22 percent of patients surviving beyond five years. The only significant independent predictor of overall survival was the time elapsed since the preceding pregnancy. It predicted survival very accurately. If more than four years had elapsed from the preceding pregnancy to PSTT appearance, 100 percent (13 of 13 women) died within five years regardless of therapy, but if presentation was within four years, 98 percent (48 of 49 women) were cured.

The authors write in conclusion: "Future studies could address the hypothesis that additional genetic changes in patients presenting at 48 months or later, compared with those presenting within 48 months, could account for the altered biology of the tumours. Consideration of time since antecedent pregnancy in the diagnosis of placental-site trophoblastic tumours could help to direct development of effective treatment strategies."

In a supplementary note, Dr Ernest I Kohorn, of Yale University School of Medicine, New Haven, CT, USA, explains that this study points out more evidently than was in the past that the greater the interval between the related pregnancy and the appearance of the tumour, the more aggressive is the disease. He says in conclusion: "Gratifyingly, today's report advocates adjuvant chemotherapy even for stage I disease."

"Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study"
Peter Schmid, Yutaka Nagai, Roshan Agarwal, Barry Hancock, Philip M Savage, Neil J Sebire, Iain Lindsay, Michael Wells, Rosemary A Fisher, Delia Short, Edward S Newlands, Manfred B Wischnewsky, Michael J Seckl
DOI: 10.1016/S0140-6736(09)60618-8
thelancet

Written by Stephanie Brunner (B.A.)
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