By Annette M. Boyle
SEATTLE — Obesity is clearly associated with poor outcomes in patients with prostate cancer, according to past research, but the reason why has remained elusive. Now a new study suggests the real culprit might be hyperglycemia, a condition commonly occurring in obese patients.
“Obesity and diabetes are correlated, but database studies that have looked at the relationship between a diagnosis of diabetes and adverse outcomes in prostate cancer have had mixed results,” said Jonathan L. Wright, MD, director of the robotic prostatectomy program at the Seattle Puget Sound VAMC, investigator at the Fred Hutchinson Cancer Research Center and assistant professor at the University of Washington School of Medicine, both in Seattle.
“We thought perhaps the yes/no diagnosis of diabetes isn’t granular enough; it may not indicate actual glucose control. We know glucose is associated with adverse breast and colorectal cancer outcomes and that cancer cells require glucose for growth,” he added, so he and his colleagues at the University of Washington dug deeper into the data.
Their analysis of the medical records of 1,734 veterans, who treated with either radical prostatectomy or radiation therapy for localized prostate cancer in VISN 20 facilities from 2001 to 2010, found that men with elevated serum glucose levels at the time of prostate cancer diagnosis had a 50% increased risk of recurrence than men with a normal glucose level. The increase in risk persisted even after adjusting for other clinical and pathological factors.1
The mean follow-up period was 41 months, with a range of 1 to 121 months, during which 16% of men had a recurrence. The 50% increase in risk associated with elevated glucose levels occurred in patients undergoing both radical prostatectomy and radiation therapy.
Glucose levels were categorized using three different methods: dividing the study population into quartiles where the lowest quartile was the referent group; using the American Diabetes Association standards for normal, impaired glucose and diabetes; and a binary analysis using the normal ADA glucose level of less than 100 mg/dl as the cutoff. All methods showed significantly increased risk in the groups with glucose levels above the “normal” threshold.
The researchers noted that the study could not determine whether hyperglycemia or subsequently elevated levels of insulin or insulin-like growth factors contributed to tumor progression, but they did observe that serum glucose levels provided a better predictor of adverse outcomes than HbA1c and were readily available for analysis. While only patients diagnosed with diabetes had HbA1c values recorded, all patients had glucose measurements.
The researchers did not track patients’ glucose control over time to see if there was a reduced risk of adverse outcomes in those who lowered their glucose levels following prostate cancer treatment.
A relationship between glucose and adverse outcomes could be good news for veterans with prostate cancer — and for the VA. “We would prefer to treat fewer patients, especially with growing concerns about over-treatment and over diagnosis,” Wright said. Patients with aggressive disease clearly benefit from treatment, but other patients are more likely to die of cardiovascular disease.
“For men with low risk prostate cancer, who are candidates for active surveillance instead of radiation or surgery,” he added, “we could potentially prescribe diet and exercise interventions that treat the cancer — and improve overall health — through glucose control.”
Wright said he favors the diabetes prevention program (DPP) diet, which has been shown to enable people to lose weight and keep weight off. “That’s something patients can do for the long term. With lifestyle changes, there’s a concern that you can’t just tell someone to exercise more and eat better. People want and need a more structured approach to be successful,” he noted.
Modestly reducing daily caloric intake can enable patients to slowly lose weight in a way that they can maintain. He suggested that education on how to shop and how to read food labels also helps many patients manage the basics of healthy eating and see improvement in their overall well-being.
Getting physicians and veterans onboard with a new approach to prostate cancer poses significant challenges, though.
Adopting watchful waiting and lifestyle changes as ways to manage and treat cancer “takes a huge shift in all providers and patients. It’s important to talk to patients before you do a biopsy, before you have results. We need to tell them that there’s a good chance that we will find cancer that we don’t want to treat and explain why. Patients need to have that context in place before they receive results,” Wright said. Otherwise patients may express a desire to proceed with unnecessary treatment out of fear and misunderstanding of the risks and benefits of treatment or watchful waiting.
Wright said he hopes to get funding to conduct follow-up on studies to determine whether diet and exercise can be shown to improve overall health and cancer recurrence and to gain further understanding of the impact of improving glucose control on cancer outcomes.
“Whether it’s diet and exercise, metformin or other medications, if glucose is the mechanism, we can intervene and have a positive impact on the men in our care by improving both cancer-specific and overall survival,” he said.
1Wright JL, Plymate SR, Porter MP, Gore JL, Lin DW, Hu E, Zeliadt SB. Hyperglycemia and prostate cancer recurrence in men treated for localized prostate cancer. Prostate Cancer Prostatic Dis. 2013 Jun;16(2):204-8. doi:10.1038/pcan.2013.5. Epub 2013 Mar 5.