Liquid Biopsy May Guide Treatment Decision in Bladder Cancer

Kate Johnson

April 22, 2014

STOCKHOLM — A blood test performed before radical cystectomy in patients with urothelial cancer of the bladder could identify the presence of circulating tumor cells (CTCs), which are predictive of outcome, according to a new study.

This "liquid biopsy" could offer valuable guidance about treatment decisions, said Michael Rink, MD, from University Medical Center Hamburg-Eppendorf in Germany.

Dr. Rink presented the findings here at the European Association of Urology 29th Annual Congress.

"The presence of CTCs was a strong predictor of outcome in patients undergoing radical cystectomy for bladder cancer who did not receive adjuvant chemotherapy," he said. These patients should be counseled about preoperative CTC findings, he added.

"Our center routinely assesses CTC status and takes the findings into account for patient counseling, but this is not routine in general clinical practice," Dr. Rink said in an interview with Medscape Medical News. "Although the evidence is growing, currently CTC status is not routinely accepted as a part of clinical or treatment decision making. Thus, our center uses CTC status as an adjunct. The true value has to be further evaluated in clinical trials."

The researchers prospectively enrolled 181 patients scheduled for treatment with radical cystectomy for urothelial carcinoma of the bladder to see whether recurrence was associated with CTC status, and whether the administration of adjuvant chemotherapy in patients with detectable CTCs affected their risk for recurrence. None of the patients had received neoadjuvant chemotherapy.

The CellSearch (Veridex) CTC test was used to analyze blood drawn preoperatively. CTCs were detected in 40 patients (22.1%).

Adjuvant chemotherapy (87% cisplatin-based) was administered to 46 patients on the basis of clinical indications and was significantly associated with younger age, advanced tumor stage, higher-grade tumor, the presence of lymphovascular invasion, the presence of microvascular invasion, and positive soft tissue surgical margins (P ≤ .045 for all). This was "obviously not completely surprising," Dr. Rink noted.

The researchers found a positive and statistically significant association between the presence of CTCs and administration of chemotherapy (= .023), and almost twice as many CTC-positive patients received adjuvant chemotherapy as CTC-negative patients (40% vs 21%).

After a mean follow-up of 30 months, the presence of CTCs predicted recurrence and cancer-specific survival in patients who received no adjuvant chemotherapy (P < .001 for both). In contrast, the presence of preoperative CTCs did not predict cancer recurrence in patients who received adjuvant chemotherapy.

On multivariate analysis, after adjustment for the common clinical and pathologic findings, the presence of CTCs was an independent predictor of disease recurrence (hazard ratio [HR], 3.94; P < .001] and cancer-specific survival (HR, 3.84; P < .003) only in patients who did not receive adjuvant chemotherapy," Dr. Rink reported.

"I think the real strength of this study is exploring the correlation of CTCs and cancer recurrence in patients who do not receive any adjuvant therapy," said Terence Friedlander, MD, from the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco.

"The authors show that after adjustment pathologic factors (including patient stage, tumor grade, lymph node metastasis, lymphovascular invasion, and margin status) the presence of CTCs prior to cystectomy was correlated with cancer recurrence and cancer-specific survival in patients with nonmetastatic bladder cancer. This is very intriguing and certainly requires confirmation in larger studies, but suggests that preoperative CTC counts could add information about the risk of recurrence for these patients," he told Medscape Medical News.

The data regarding the impact of adjuvant chemotherapy are a bit more challenging to interpret, noted Dr. Friedlander, who was coauthor of a recent review on the role of CTC analysis in metastatic disease (Pharmacol Ther. 2014;142:271-280).

"Did adjuvant therapy prevent recurrence in these patients, or were they just very high-risk to begin with and it did not matter whether CTCs were detectable? Higher CTC counts appear to be associated with higher-risk disease, but it is not clear from this study whether the presence of CTCs alone is enough (as opposed to high-risk clinicopathologic findings currently used in clinical practice) to tell a clinician whether to add adjuvant chemotherapy," he explained.

Dr. Rink and Dr. Friedlander have disclosed no relevant financial relationships.

European Association of Urology (EAU) 29th Annual Congress: Abstract 117. Presented April 13, 2014.

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