Promising Blood Test for Bladder Cancer Doesn’t Work, Researchers Find

Neutrophil-to-lymphocyte ratio flops in UPenn study

A blood test that has shown promise in predicting how cancer will progress and what treatments will be most effective for a given patient may not be reliable for either, according to a study from the University of Pennsylvania’s Perelman School of Medicine.

Investigators have been looking for a biomarker in bladder cancer, and one emerging candidate is the neutrophil-to-lymphocyte ratio (NLR). Previous studies have linked an elevated NLR with worse overall survival after radical cystectomy. Other studies suggested that the NLR correlates with the amount of cancer found during surgery, meaning the blood test might predict which patients will benefit from presurgery chemotherapy to shrink their tumors.

But new research led by Eric Ojerholm, MD, has raised doubts about the NLR as a biomarker. In contrast with previous studies, Ojerholm and his team found that the NLR is not effective at predicting the overall survival of patients with muscle-invasive bladder cancer. Further, they found that the NLR was not helpful in determining which patients would benefit from chemotherapy before surgery.

Ojerholm said the discrepancy between the findings of the new study and previous work comes in the methodology.

“Dozens of earlier studies reported NLR as a biomarker for bladder cancer, and we hoped that this would be true,” Ojerholm said. “Yet extraordinary claims require extraordinary evidence. And all prior studies relied on observational datasets. Many also used statistical methods that can lead to false positive results. So we decided to rigorously put NLR to the test.”

Ojerholm and his team analyzed data that were collected in real time during a prospective clinical trial, making their study of the NLR in bladder cancer the first one that did not rely on observational findings.

The new study analyzed the SWOG 8710 trial, a randomized phase 3 study of 317 patients with muscle-invasive bladder cancer. All of the patients were treated with radical cystectomies. Half of the patients had presurgery chemotherapy, and the other half did not.

Of the 317 patients, Ojerholm and his team identified 230 for a prognostic analysis to see whether the NLR could serve as a predictor of how long patients would survive after curative treatment. They identified 263 other patients for a predictive analysis to see whether the NLR could tell which patients would respond to chemotherapy. The median follow-up period was 18.6 years.

The investigators found that, for the prognostic analysis, the NLR was not a significant factor in overall survival. The important factors were age and whether the patient received presurgery chemotherapy. Moreover, for the predictive analysis, the NLR did not predict which patients benefitted from chemotherapy. The findings were published in Cancer.

On the question of why most previous publications supported the NLR as a biomarker, Ojerholm pointed to several factors beyond methodology and statistical design.

“There’s also the problem of publication bias,” he explained. “Sometimes authors won’t submit negative results, and sometimes journals won’t accept them. That could be a real issue as NLR research continues.”

Ojerholm stressed that no single study is definitive, and that doctors must weigh results from the entire literature.

“Yet this study does raise questions about NLR for bladder cancer,” he added, “and we need more evidence before using this biomarker in clinical practice.”

Source: Perelman School of Medicine; October 27, 2016.