Biomarker changes may predict bladder cancer outcomes

April 1, 2007

Assessment of a set of four apoptosis markers in patients with urothelial-cell carcinoma of the bladder appears helpful for predicting which patients are at elevated risk for disease recurrence and disease-specific mortality after radical cystectomy and bilateral lymphadenectomy.

Key Points

Dallas-Assessment of a set of four apoptosis markers in patients with urothelial-cell carcinoma of the bladder appears helpful for predicting which patients are at elevated risk for disease recurrence and disease-specific mortality after radical cystectomy and bilateral lymphadenectomy, according to researchers from the University of Texas Southwestern Medical Center, Dallas.

Risks of recurrence and mortality increased progressively with increases in the number of altered biomarkers, and the difference compared with the reference group of patients who had no such alterations achieved statistical significance in those who had all four biomarkers altered. In that highest-risk group, rates of recurrence-free survival and disease-specific survival after 7 years were only 9% and 8%, respectively, as reported in the February issue of The Lancet Oncology (2007; 8:128-36).

"Current prognostic markers for muscle-invasive bladder cancer, such as tumor grade, stage, and lymph node status, are not accurate enough for predicting risks of recurrence and death after radical cystectomy," said first author José Karam, MD, in an interview with Urology Times. "The findings of our retrospective study suggest that assessment of these four biomarkers might offer additional information and, in particular, offer a method for identifying patients with a very poor prognosis.

Role of apoptosis defined

Recognizing the importance of abnormalities in apoptotic mechanisms in the pathogenesis of malignant disease, previous investigators have studied their role as prognostic biomarkers. However, those investigations have focused mostly on single markers and have suffered from other methodologic limitations.

"We reasoned that apoptosis is a complex process likely to be underestimated by evaluation of single proteins involved in the regulatory pathway. Our study is the first to investigate these four proteins in combination," Dr. Karam explained.

All patients included in the study had undergone surgery for their bladder cancer at UT Southwestern between January 1987 and December 2002. None had distant metastases at the time of surgery. The duration of postoperative follow-up ranged from 1 to 183 months, with a median of almost 37 months. Rates of recurrence and disease-specific mortality in the study population were 45% and 36%, respectively.