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Circulating Tumor Cells As Indicators Of Prostate Cancer Status

A new study suggests that monitoring circulating tumor cells (CTCs), the cells that have broken free from the tumor, may be a useful way to assess the status of prostate cancer that is more reliable than the PSA (prostate specific antigen) test, although the findings would need to be confirmed in clinical trials, said the authors.

The study was the work of researchers at the Memorial Sloan-Kettering Cancer Center in New York, other research centers in the US and the Royal Marsden Hospital in London, UK, and is published in the early online issue of the The Lancet Oncology on 11 February.

The main purpose of the study was to find another way to monitor progress in drug trials that gives reliable intermediate results so that approval timescales can be shortened. The authors decided to investigate whether measuring CTCs might be a useful way to predict survival in patients who are undergoing chemotherapy to treat progressive prostate cancer that has started to spread.

For the study, the researchers identified 164 men with progressive metastatic castration-resistant prostate cancer who were undergoing first line chemotherapy in the IMMC38 trial. In this trial, the CTCs were isolated from blood samples using a method called immunomagnetic capture; this was done at the start and end of the trial.

The researchers analysed the association between survival and the before and after values of a number of variables, including CTC count, levels of PSA, lactate dehydrogenase (LDH) and others, and assessed how well they identified patients at high and low risk of survival.

The results showed that:

* Variables linked to a high risk of death included: high LDH, high CTC, and high PSA, low albumin and low haemoglobin at baseline (start of study).

* After 4 weeks, 8 weeks and 12 weeks, changes in CTC counts were strongly linked to risk, whereas PSA was not.

* The strongest predictors for survival were LDH concentration and CTC counts.

The authors concluded that:

"CTC number, analysed as a continuous variable, can be used to monitor disease status [of prostate cancer] and might be useful as an intermediate endpoint of survival in clinical trials. "

They suggested the results were strong enough to warrant "prospective recording of CTC number as an intermediate endpoint of survival in randomised clinical trials".

Commenting on the findings, John Neate, Chief Executive of The Prostate Cancer Charity in the UK told the press that:

"Once prostate cancer has advanced to the stage where chemotherapy is an option -- which is at a late stage of the disease, unlike in many other cancers -- one of the problems that doctors face is uncertainty about the effectiveness of the treatment. "

He said that current tests aren't very effective at tracking progress of the disease in chemotherapy, they work reasonably well, but something better is needed, he said.

"Whilst further trials are necessary, this new research shows that measuring the number of circulating tumour cells seems to improve prediction of how men will respond to chemotherapy," said Neate, adding that measuring CTCs seems to be:

"More finely attuned to the effects of the chemotherapy than previously thought. There are, therefore, circumstances where some men will benefit from further courses of chemotherapy treatment when at present they may not be offered it," explained Neate.

He also said that a more accurate measure may help to reduce the anxiety that comes when there is insufficient clarity about the progress of the disease adding to the difficulty of deciding if the treatment is working or not.

"Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data."
Howard I Scher, Xiaoyu Jia, Johann S de Bono, Martin Fleisher, Kenneth J Pienta, Derek Raghavan, Glenn Heller.
The Lancet Oncology, Early Online Publication, 11 February 2009.
doi:10.1016/S1470-2045(08)70340-1