GTD

Question:
GTD Patient.

3/10/06…Evacuation Complete Mole …..Chest X Ray normal
Review of Path =Complete Mole although had a fetus seen on scan with a heart beat 25/8/06!

HCG fell to normal by 8/1/2007….started to rise and was 29 by 1/10/2007 when referred.…urinary HCG also raised.

Levels rose slowly until seen in Feb 2008 with HCG now 63.  Given 5 cycles of MTX/FA levels never normal ……got to 11.9 and then started to rise and reached 125 by the end of August 2008.

Commenced on EMACO…..Results normal after one full cycle and given 2 further full cycles finishing at the end of November 2008

Results normal until 2/6/09 when HCG rose to 32 and she elected to have a Hysterectomy despite a negative metastatic work up. Surgery on 16/6/09.Negative histology.

Now…HCG 48 on 3/7/09 and 60 on 10/7/09

WHAT NEXT??

Michael Quinn


 
Response # 1:
Dear Michael,

 Thank you for asking me about this case. How old is she? Parity? She has classical "Quiescent Gestational Trophoblastic Disease". If you go to the net and look for publications by Cole LA you will find numerous descriptions of this (new) syndrome.

Elevated hCG usually after a trophoblastic event with no clinical or imaging evidence of tumor with no effect of therapy, chemotherapy or surgery. The key to diagnosis is to obtain  the value of hyperglycosylated hCG (hCG-H) as a percentage of total hCG. hCG-H is the invasive cytokine in both normal pregnancy and choriocarcinoma/GTN. The trophoblast tumor will not become sensitive to therapy until the hCG-H becomes elevated above 40% of total hCG. We've had quite a bit of experience with such cases. They get treated unnecessarily and inappropriately with no effect during the quiescent period.

Laurence Cole is the expert on this and provides an efficient testing service at the University of New Mexico. A generally available test kit is coming on the market but I'm not sure is yet available. I would contact Dr Cole and send him serum and urine samples from the patient by FEDEDERAL EXPRESS MAIL and he will provide the data in a few days.

This patient should not have further therapy until the hCG-H percentage is known. Her tumor will become sensitive to chemotherapy when the hCG-H rises to
 greater than 40% of total hCG. I hpe these coments are helpful to you. Best wishes and please keep me posted on what happens.

Ernest Kohorn
 

Response # 2:
PET CT in order to look for a MTS
If negative wait and performe a new check a month later or in case of clinical evidence of recurence.
In alternative re-start with chemo (EMACO) using the marker to define the response.
I support  the first choice.

Paolo Zola
 

Response # 3:
Dear Michael,
 
I once had a similar patient. Finally she had placental site tumor not reacting very well on chemotherapy with one lung metastasis - we took it out and since then, the patient never had hCG elevated. She had failed three regimens including yours + EMA-EP. The lung nodule was detected by PET-CT.
 
So, if detectable and feasible, I would consider surgery. Otherwise I would re-start chemotherapy, probably with EMA-EP
 
Andreas du Bois
 
PS: the obstetrician/ultrasounder should work up his findings.
 
Response # 4:
Hi Mason and Michael,

After consultation with others around here we think there are a few possibilities.

-1. The rise in HCG may be caused by HAMA antibodies, but then the response to MTX and EMACO was not expected. It would be nice to be able to examine a bloodsample with assay used here, or in Charing Cross.

-2. A non mole malignancy producing HCG, has breast, ovary, and GI cancer been ruled out?

-3. The most probable cause is a GTN (choriocarcinoma, PSTT or persistent trophoblast). A PET scan may be of help to find any localization (few case reports showed paraaortic nodes in such cases), especially since HCG is rising faster now than before.

Hope this is of help to you.
 
Cheers and regards,

Ruud L.M. Bekkers

Response # 5:
After a negative metastatic work up and hysterectomy with negative pathological findings, we suggest that now we must exclude first a phantom hCG elevation.  hCG levels must be measured in both blood and urine. Samples could be sent to the hCG Referans Service or laboratory.  Also, the presence of lack of dilutional parallelism and absence of urine reactivity could be indicated that the molecule measured was a pseudogonadotropin or phantom hCG, an interfering substance in hCG tests.

If diagnosis of a phantom hCG was made we must continue to follow up patient without any cytotoxic treatment.

The second concept is the “persistent low levels of hCG”, this condition is named quiescent GTD. By definition,  the patient has had persistent low levels of hCG present for 3 months or longer with no clear increasing or decreasing hCG trend. No disease is detectable clinically or by sophisticated imaging. In most cases, the patient has been treated with singe agent chemotherapy and when the hCG fails to decrease, combination chemotherapy and/or hysterectomy. According to the studies these patients have residual syncytiotrophoblast cells with no or very minimal invasive cytotrophoblast cells and therefore have active disease. Depending on Cole’s and many other studies, 10-25% of these quiescent GTD cases, persistent hCG concentration changes and starts to elevate rapily 5 months to 10 years after the findings of the persistent elevated hCG. In most of these cases, a tumor is subsequently identified, with pathology indicating choriocarcinoma or other GTN. This results indicates that quiescent  is a premalignant syndrome with malignant transformation occurring in a proportion of cases.

Hyperglycosylated hCG (hCG-H) mar aid in the identification of quiescent GTD and the early detection of onset of active disease. hCG-H is produced predominantly by invasive cytotrophoblast cells.

Next step for our case will be test for “hyperglycosilated hCG”. Test result can help us to discriminate between GTN/choriocarcinoma and quiescent GTD and of course need for chemotherapy or simply follow the patient.

Prof . Ali Ayhan M.D.
On behalf of Turkish Society of Gynecologic Oncology (TRSGO)