Obese men with prostate cancer are at higher risk for treatment failure after primary radiation therapy, according to a study in the August 1 issue of Cancer. The research indicates that each incremental increase in body mass index (BMI) increased the risk for clinical or biochemical failure. The study is the first to investigate the association between obesity and post-radiotherapy outcome.
“This relationship might exist because of complex interactions of hormonal and growth factors, as well as association with lifestyle factors including diet or physical activity,” said lead author Sara Strom, PhD, Associate Professor of Epidemiology at the University of Texas M. D. Anderson Cancer Center in Houston.
The researchers postulate that fat tissue influences concentrations of various significant signaling molecules, such as testosterone, estrogen, insulin and insulin-like growth factor, which play a role in prostate cancer development and progression.
To determine whether obesity was an independent predictor of biochemical failure and clinical recurrence among patients treated with external-beam radiotherapy, Dr. Strom and her colleagues performed a retrospective analysis on 873 patients receiving that as the sole treatment for localized prostate cancer between 1988 and 2001. Among the group, 18% were mildly obese and 5% were moderately to severely obese.
After an average 96 months of follow-up, 295 (34%) of the men had three consecutive increases in blood prostate-specific antigen (PSA) levels, indicating biochemical failure. Meanwhile, 127 (15%) of the men had clinical failure, meaning local recurrence and/or distant metastasis, determined by radiologic studies, biopsy, or physical examination.
Patients who had progression and biochemical and clinical failure were diagnosed at a younger age and were more likely to have presented with more advanced disease (higher clinical stage, Gleason score, and a pretreatment PSA over 10 ng/mL) compared with those who did not have disease progression.
Those with progression also received a significantly lower radiation dose and were diagnosed in earlier years than those men whose disease did not progress.
The risk of biochemical and clinical failure was found to be influenced by BMI. As BMI increased, the risk of disease progression following therapy also increased. For example, men who were moderately or severely obese were at double the risk for biochemical failure than other men who were not.
‘New but Not Unexpected’
“This was the first paper to look at treatment outcomes and to include not just PSA scores but also metastatic disease status,” said Stephen Freedland, MD, Assistant Professor in the Department of Surgery, Division of Urology at Duke University School of Medicine and the Duke Prostate Center.
The correlations between outcomes and these two factors were the same, he noted. “This is new but not unexpected.”
This was a medical review of men who have already been treated, which is a limitation, Dr. Strom noted. In addition, there is a possibility the some techniques used in the radiation therapy may not have been optimal for obese patients.
One of the study limitations was that 90% of patients were white, while African-American men were more likely to be obese, Dr. Freedland noted. However, there weren't enough black patients on study to evaluate them separately. Among the 873 patients included in the analysis only 71 were African-American.
Growing Body of Evidence
There is already a body of scientific evidence demonstrating that obesity is linked to treatment failure after prostatectomy, Dr. Strom noted.
Dr. Freedland said that the study adds to the growing literature showing that surgical patients who are obese are at an increased risk of poor outcomes. Some researchers claim that poorer outcomes are due to the difficulty of performing surgery on obese patients, while others think these outcomes are the result of obesity causing more aggressive disease, he explained.
This new study supports the argument that the obesity itself contributes to poorer outcomes rather than the treatment, although radiation can sometimes be difficult to administer in these patients, he said.
Among the many unanswered questions are the specific biological reason for why obesity would affect outcomes, Dr. Strom said. “We need to understand the mechanisms underlying the relationship between obesity and prostate cancer outcome.” Researchers need to identify the pathways and genes that shape this relationship and develop targeted therapy.
Future studies should evaluate the relationship of obesity with dietary factors, genetic modifiers of steroid androgen metabolism, insulin, and a detailed investigation of the insulin growth factor pathway to explore the underlying mechanisms of action in prostate carcinogenesis, Dr. Strom and her coauthors wrote.
Also to be determined is whether obese men with more aggressive disease need to undergo more aggressive therapy, Dr. Freedland said. “Should they routinely have radiation combined with hormonal therapy, and should they undergo higher doses of radiation?”
There is strong evidence that if a patient is obese and has prostate cancer, he's more likely to have aggressive cancer, Dr. Freedland said. “The big question is if patients lose weight, will this improve their outcomes and will they have less aggressive cancer? “We don't have the answer, although intuitively, I want to say yes.”
Behavioral interventions such as nutrition and exercise may help in reducing the disease progression, as well as the development of other illnesses such as diabetes or heart disease, Dr. Strom.
Because losing weight is beneficial for the heart, Dr. Freedland recommends that his obese patients try to lose as much as possible—“And it doesn't hurt their cancer either,” he said.
In conclusion, Dr. Strom said, obese men with prostate cancer should be aware of the poorer outcomes associated with their BMI and discuss this issue with their doctor when they choose treatment—“They need to have an open discussion with their urologist about the possible implications.”
Research Misconduct Increases in 2005 after 2004 Downturn
According to the NIH Office of Research Integrity, a record number of institutions reported a record number of new research misconduct cases last year, following a downturn in 2004.
Eighty-five institutions reported 114 new cases. The previous highs were 82 institutions reporting 105 new cases in 2003, and in 2004, there were 63 institutions with 81 new cases.
Research misconduct activity is defined as receipt of an allegation or conduct of an inquiry and/or investigation. Reportable activities are limited to alleged research misconduct involving Public Health Service-supported research, research training, or related activities.
The 85 institutions that opened new cases in 2005 did so on receipt of 133 allegations (69 for falsification, 31 for fabrication, and 33 for plagiarism) that resulted in 79 inquiries and 36 investigations. These cases arose in institutions of higher education, research organizations, other health organizations, independent hospitals, and a small business.