External beam radiation therapy patients may have higher risk for later mortality

November 1, 2008

Prostate cancer patients who received radiation therapy were almost twice as likely to develop a secondary malignancy.

Sacramento, CA-Patients who undergo external beam radiation therapy (EBRT) either as primary treatment for prostate cancer or for post-prostatectomy positive margins are at increased risk of mortality if they later develop bladder or colorectal secondary malignancies, according to researchers from the University of California, Davis.

The researchers, presenting at the AUA annual meeting in Orlando, FL, said that when patients with locally advanced or metastatic disease were excluded, only those who later specifically developed bladder and colorectal cancers were significantly negatively impacted in terms of overall and secondary malignancy-specific survival.

Patients who received radiation were almost twice as likely to develop a secondary malignancy compared with those who were not exposed (odds ratio, 1.89; 95% confidence interval, 1.85-1.95).

"The argument as to whether there is an increased risk of bladder and colorectal cancers among those treated with EBRT is primarily one of statistical analysis-simple odds ratio versus Cox proportional type hazard models," Dr. Chamie said.

The UC Davis group, however, took the analysis to the next level, examining disease-specific survival after radiation treatment. Dr. Chamie and his team found that secondary malignancy-specific survival was significantly worse in patients treated with EBRT who developed bladder or colorectal cancers.

Conversely, radiotherapy for prostate cancer was not associated with worse secondary malignancy-specific survival in men who developed renal, respiratory, hematologic, small intestine, or hepatobiliary cancers.

"Many will argue that there is a fair amount of selection bias here, since patients who are not good surgical candidates tend to undergo EBRT," Dr. Chamie noted.

To address that charge, the investigators also specifically considered patients who underwent surgery and radiation versus surgery alone, the assumption being that those who had both therapies must have been relatively healthy.

"Our results were the same," Dr. Chamie said. "Those patients who underwent surgery and then radiation had worse overall and disease-specific survival with regard to the secondary bladder and colorectal cancers than those who underwent surgery alone.

"When we asked how it impacted survival, we found a real increase in [secondary] cancer incidence and a slight (7%) increase in T-stage. But the biggest factor is that patients treated with radiotherapy to the pelvis are less likely to undergo extirpative measures for their invasive colorectal or bladder cancer."

Indeed, patients who have undergone EBRT are more than 45% less likely to undergo a cystectomy for muscle-invasive bladder cancer than those who do not have radiation, Dr. Chamie said.

EBRT still has value

Data for the study were culled from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The cohort included 130,375 prostate cancer patients treated with EBRT and 375,235 who did not receive radiation. Exclusion criteria included brachytherapy, unknown radiotherapy, previous malignancy, and development of a new malignancy within 1 year of initial prostate cancer diagnosis.

Dr. Chamie stressed that the results in no way constitute a call to abandon radiotherapy for prostate cancer.

"However," he said, "it does raise a question about patients who have a positive surgical margin after prostatectomy without an elevation in PSA. While adjuvant radiotherapy for treatment of margin-positive disease has been shown to have long-term benefit, no one has addressed secondary malignancy."

Until researchers can identify biomarkers associated with the development of secondary cancers, he said, "We should be cautious about those we irradiate for positive margins without PSA elevation."