New Method To Monitor Disease Status Of Patients With Advanced Prostate Cancer, The Lancet Oncology

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 15 Feb 2009 - 0:00 PDT

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Survival and response to treatment in patients with advanced prostate cancer can be predicted by assessing changes in the number of circulating tumour cells (CTCs), according to an Article published Online First and in the March issue of The Lancet Oncology.

Prostate cancer is one of the most common types of cancer to affect men, particularly in the USA and Europe. It is usually associated with individuals over the age of 50 years. When hormonal therapy ceases to be effective, a patient is deemed to have castration-resistant prostate cancer. The progress of such disease is very difficult to track, as is the prediction of how patients will respond to chemotherapy.

Professor Howard Scher (Memorial Sloan Kettering Cancer Center, New York City, USA) and colleagues assessed the association between CTC number (both before and after treatment) and survival, and also evaluated other factors such as changes in the prostate-specific antigen (PSA) and baseline lactate dehydrogenase (LDH), in 164 patients embarking on first-line chemotherapy regimens. CTC number was determined using the US Food and Drug Administration-approved Cell Search™ (Veridex) system.

The researchers found that, before treatment, high values of CTC number and PSA were associated with increased risk of death. However, after treatment, as assessed at 4, 8, and 12 weeks, changes in CTC number were strongly associated with risk, whereas changes in PSA were only marginally associated. The study confirms that pre-treatment CTC number can be used to predict survival of patients starting first-line chemotherapy, and that it can also be used to monitor disease status and response to treatment. It is more predictive than PSA both before and after treatment.

"CTC number … can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials", said Scher. "Use as an intermediate or surrogate endpoint for survival could shorten the timeline for drug approval", although he notes that "several prospective trials are needed to generate evidence to guide the use of biomarkers". He added that the model that best predicted survival incorporated pre-treatment CTC number and LDH concentration alongside post-treatment changes in CTC number.

- CTCs were isolated by immunomagnetic capture from blood samples drawn at baseline and after the initiation of first-line chemotherapy. Kaplan-Meier analysis was used to estimate survival. The association between biomarkers and survival was tested with Cox proportional hazard models.

- Currently, changes in PSA concentration are used to guide decisions in treating castration-resistant prostate cancer, but this is not effective in predicting the clinical benefit of therapy.

- The US FDA has approved the use of a test involving CTC number-as determined by the Cell Search™ (Veridex) system-to help monitor patients with metastatic prostate cancer. The method works by treating baseline and post-treatment CTC numbers as discrete rather than continuous variables. Cut-off values determine whether patients fall into 'favourable' or 'unfavourable' groups. Patients who remain in the 'unfavourable' range after treatment, regardless of their baseline CTC value, are considered unsuitable for continued therapy. Scher and colleagues' findings argue against the use of discrete cut-off values, and for the maintenance of treatment in circumstances where the CTC number is stable or falling and there are no other signs of deterioration.

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

The Lancet

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