Two Predictors of Prostate Cancer Explored in Healthy Men

STOCKHOLM, Sweden — Two studies presented at the 2011 European Multidisciplinary Cancer Congress held jointly by ESMO/ECCO have enhanced understanding of risk factors for prostate cancer.

The first study found that men with benign prostatic hypertrophy (BPH) are at increased risk of prostate cancer and of prostate cancer-related mortality. The second trial found that monitoring prostate-specific antigen (PSA) levels in healthy men at age 40 or 45 can predict long-term risk of prostate cancer and prostate cancer-related mortality. Both studies were led by David Orsted, Copenhagen University Hospital, Herlev, Denmark.

Commenting on the first study, co-author Stig Bojesen, MD, said, “BPH and prostate cancer are the most common conditions of the prostate, with a large number of incident and prevalent cases each year. A possible association [between the two conditions] has been debated for several years, but previous studies have had ambiguous results. Our study is the largest to date [to look at this association], and has consistent results.”

Growth of the prostate depends on hormone levels in both prostate cancer and BPH, and both conditions are treated with anti-androgen agents. “It has been controversial whether BPH leads to prostate cancer, but this study provides strong epidemiologic evidence of an association. However, one cannot extrapolate causation from this study,” Orsted commented.

The study analyzed the association between BPH and eventual development of prostate cancer from the years 1980 to 2006 in a total of 3 million-plus Danish men enrolled in five national registries. The researchers looked at men who were hospitalized and those who were surgically treated for BPH. Among this population, 53,315 men were diagnosed with prostate cancer and 25,459 deaths were attributed to prostate cancer. The reference group included about 2.7 million men without BPH.

Over 26 years, the presence of BPH was associated with a 2- to 4-fold increased risk of developing prostate cancer and a 2- to 8-fold increased risk of men with BPH dying from prostate cancer.

The implication of the study, according to Bojesen, is that physicians who treat men with BPH who require hospitalization and surgery should follow these men carefully to ensure early diagnosis of prostate cancer and timely treatment. “However, the optimal surveillance program for these men should be addressed in future studies,” he said.

The Copenhagen City Heart Study

In the second study, the authors studied 4,383 men between the ages of 20 and 94 years who participated in the Copenhagen City Heart Study. Baseline levels of PSA were obtained and samples were stored for 30 years; in 2010, 170 men developed prostate cancer, and 94 of them died of the disease. A stepwise increase in baseline PSA levels predicted a 3 to 44-fold increase in risk of prostate cancer and a 2 to 12-fold increase in risk of prostate cancer-related mortality.

The absolute 10-year risk of developing prostate cancer was 11%-22% in men with PSA levels of 4.01-10 ng/mL and 37%-79% in men with levels above 10 ng/mL. Men with PSA levels of 2 ng/mL or lower, who comprised 90% of the sample, were at very low risk of future prostate cancer.

Prostate cancer is over-diagnosed, and the general benefit of PSA screening is limited. This study suggests that screening efforts should be focused on men with higher baseline PSA levels, while men with lower baseline PSA levels could avoid frequent and unnecessary prostate biopsies and digital rectal exams.

“Measuring PSA levels at age 40 or 45 could identify men who are at high risk and should be screened at regular intervals. I think we can select men better and do more focused screening of high-risk individuals We can use these epidemiologic data to develop guidelines. But we can also reassure men with very low PSA levels that they are at an absolute low risk of prostate cancer. This study suggests that general practitioners may not have to screen as many men. PSA screening should be done at age 40 to 45 years, and then the first measurement of PSA may be used to determine whether or not future screening is needed. This is not the way screening is done now,” Orsted said.