In Bladder Cancer, ERCC1 Status Predicts Chemo Response

Kate Johnson

April 15, 2014

STOCKHOLM — Patients with bladder cancer who are treated with neoadjuvant chemotherapy before radical cystectomy have significantly better survival if their tumors test positive for ECCR1, a protein involved in DNA repair, new research suggests.

The finding could help guide decisions about which bladder cancer patients receive presurgical chemotherapy, said investigator Tammer Hemdan, MD, from University Hospital Uppsala in Sweden.

European Association of Urology (EAU) guidelines highly recommend neoadjuvant chemotherapy before cystectomy, "but the number needed to treat is high and the subset of patients likely to benefit using clinical analysis has not been identified," he explained.

"In advanced bladder cancer, patients are more than likely elderly, frail, and marked by their disease," Dr. Hemdan told Medscape Medical News. "Being told that cystectomy with urinary deviation is their best option, plus preoperative chemotherapy that may or may not better their chances for a successful survival, is not an easy choice. We hope, with this ERCC1 marker, to identify the biological tumor profile as a good or poor responder to preoperative therapy, thus helping during preoperative preparation."

Dr. Hemdan presented the findings here at the EAU 29th Annual Congress.

The investigators analyzed tumor specimens from 244 patients with T1 to T4 bladder cancer in 2 trials that compared neoadjuvant cisplatin-based chemotherapy plus surgery with surgery alone.

Immunohistochemistry was used to determine the ERCC1 status of the samples; 76% tested positive.

For patients treated with surgery alone, overall survival was substantially lower when ERCC1 status was negative than when it was positive (P = .005).

For patients treated with neoadjuvant chemotherapy plus surgery, ERCC1 status did not influence survival rates, resulting in a 45% improvement in survival for ERCC1-negative patients.

Because ERCC1-negative patients benefit from neoadjuvant chemotherapy, "they should be offered more of it because the DNA-damaging effect is very substantial in those patients," Dr. Hemdan explained.

In most labs, the immunohistochemistry analysis required to identify ERCC1 is commonly used and could be performed on the biopsy sample. Therefore, "determining ERCC1 expression should be simple and rapid," he said.

"This is really fantastic work," said Tim O'Brien, MD, from Guy's and St Thomas' Hospital in London, United Kingdom, after the presentation. "It goes toward that goal of individualized patient care, where one is directing potentially toxic treatments only to people who will benefit from them. Very, very enticing."

"Personally, I think these chemo treatments are too toxic and too expensive to give to everybody. We need a method of defining who responds," Dr. O'Brien told Medscape Medical News.

"One of the worries about giving chemo that doesn't work — apart from making people feel unwell — is that it shatters the immune system and delays cystectomy by 3 months," he explained. In addition, "it probably does harm to those who don't respond, so it's really important that you target treatments only at the people who are going to respond."

"ERCC1 is a DNA repair gene and cisplatin causes DNA damage, so if you don't possess the gene you can't repair the damage," he noted. "I think this is a way to identify people who probably should be getting chemo, and perhaps people who definitely shouldn't."

Dr. Hemdan and Dr. O'Brien have disclosed no relevant financial relationships.

European Association of Urology (EAU) 29th Annual Congress: Abstract 122. Presented April 12, 2014.

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