CHICAGO, April 27 — A man’s PSA value at age 60 reliably predicted the risk of fatal prostate cancer over the next 25 years, according to data from a Swedish study.

• Explain to patients that this study showed that a man’s PSA value at age 60 predicted the risk of dying of prostate cancer to age 85.
• The findings require validation in other patient populations.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Men who had PSA values below the median of ?1 ng/mL had less than a 1% risk of dying of prostate cancer by age 85, Hans Lilja, M.D., of Memorial Sloan-Kettering Cancer Center in New York, reported at the American Urological Association meeting.

At the other end, the risk of fatal prostate cancer soared into double digits in men who had a PSA value of 3 to 4 ng/mL or higher at age 60.

“Sixty-year-old men with PSA at or below the population median can be advised that although they may harbor cancer, it is unlikely to become life threatening,” said Dr. Lilja. “Those with PSA elevated above thresholds such as 3 or 4 ng/mL are at greatly increased risk of clinically diagnosed prostate cancer and prostate cancer-specific death.”

Men with PSA values below those that trigger prostate biopsies have a substantial risk of developing prostate cancer. However, the clinical focus should be on men who have an increased risk of developing symptomatic or fatal prostate cancer, not prostate cancer per se, said Dr. Lilja.

“Screening and chemoprevention in men age 60 and above should focus on subgroups of men with PSA levels strongly associated with symptoms or death,” he asserted.

To investigate the relationship, researchers analyzed data from the Malmo Prevention Project, a study of cardiovascular disease conducted from 1974 to 1986 in Malmo, Sweden. PSA testing was uncommon at that time, but frozen plasma samples from study participants permitted PSA assessment more than two decades later.

The analysis included 1,167 men who were born in 1921 and whose blood samples were obtained during 1981 and 1982. Researchers followed the men until death or age 85, whichever came first.

Dr. Lilja said 133 men (11.4%) developed prostate cancer during follow-up, and 31 men (2.7%) died of prostate cancer.

The median PSA value for the entire study group was 1.06 ng/mL. Men who had PSA values at or below the median at age 60 had a 0.3% risk of prostate cancer death by age 85.

The risk of dying of prostate cancer by age 85 increased to 1.5% in men whose PSA value was 1.5 ng/mL at age 60 (67th percentile). Prostate cancer mortality increased to 3.7% in men who had a PSA level of 2.1 ng/mL at age 60 (80th percentile).

From 2.1 to 3.4 ng/mL (90th percentile), the risk of fatal prostate cancer increased to 8.9%. The risk almost doubled to 15% with a PSA value of 5.2 ng/mL at age 60 (95th percentile) and doubled again to 31% with a PSA value of 15 ng/mL (99th percentile).

Two thirds of prostate cancer deaths involved men who had PSA values ≥3.4 ng/mL. A PSA value of 1.5 ng/mL at age 60 identified 90% of the men who would subsequently die of prostate cancer. The median value for the study population (1.06 ng/mL) comprised 93% of all prostate cancer deaths.

Dr. Lilja said the findings must be reproduced in other populations before they can be applied to clinical practice.

Dr. Lilja and colleagues reported no competing interests.

Primary source: American Urological Association

Source reference:
Vickers AJ, et al “Prostate-specific antigen level at age 60 and death from prostate cancer” AUA 2009; Abstract 162.

CHICAGO, April 28 — Men who were taking statins at the time of radical prostatectomy had a 30% reduction in prostate cancer recurrence, data reported here showed.

Statin users also had lower PSA values and were more likely to have T1 disease than nonusers, Robert J. Hamilton, M.D., of the University of Toronto, said at the American Urological Association meeting.

“Our findings suggest that statins may slow prostate cancer progression after radical prostatectomy,” said Dr. Hamilton. However, he emphasized, “at this point we cannot say with confidence that statins reduce the risk of prostate cancer recurrence after radical prostatectomy.”

He said the findings require confirmation in other studies, such as a randomized controlled trial placing men on statins who are about to undergo surgery.

• Explain to patients that use of statin drugs has been associated with benefits related to several urologic conditions.
• All of the data came from retrospective studies of databases and therefore do not prove that statins are beneficial for the conditions.
• Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Dr. Hamilton’s study was one of a half-dozen statin-related abstracts featured at an AUA press briefing. Collectively, the studies suggested that statins have favorable effects on prostate cancer risk, lower urinary tract symptoms (LUTS), benign prostatic hyperplasia (BPH), and erectile dysfunction.

Dr. Hamilton reported findings from a study of 1,325 men who underwent radical prostatectomy for prostate cancer. Information collected before surgery included current statin use — 237 (18%) men were taking one of the drugs at the time of surgery. The principal outcomes were pathologic features of the cancer and biochemical recurrence.

There were no differences between those taking statins and those not taking the drugs with respect to the frequency of positive surgical margins, seminal vesicle invasion, extracapsular extension, or lymph node metastases. However, significantly more statin users had a Gleason score of 7 (60% versus 49%, P=0.003).

Statin users presented a mixed bag of risk characteristics. They had a lower mean PSA value (6.2 ng/mL versus 6.9 ng/mL, P=0.04), and 67% of statin users had stage T1c disease compared with 58% of nonusers (P=0.009).

On the negative side, statin users were 2 years older and had a higher rate of obesity, as well as the higher proportion of Gleason 7 disease.

In a multivariate analysis, statin users had an odds ratio for recurrence of 0.70 compared with nonusers (95% CI 0.50 to 0.97, P=0.03).

Adding to statins’ association with prostate cancer, Lionel Banez, M.D., of Duke University in Durham, N.C., reported findings from an analysis of obesity, statin use, and tumor inflammation.

Mounting evidence suggests inflammation may play a role in prostate cancer evolution and progression. Obesity has been associated with inflammation and more aggressive cancer, Dr. Banez said. Statins, on the other hand, have well-documented anti-inflammatory activity and have been associated with reduced cancer risk.

Dr. Banez and colleagues reviewed data on 254 men who underwent radical prostatectomy. About half of the patients reported statin use.

One pathologist graded all of the surgical specimens with respect to inflammatory infiltrates.

Significantly more statin users were overweight (48%) and obese (31%, P<0.001). However, increasing body mass index had only a marginal association with inflammation (OR 2.16, P=0.07).

In a multivariate analysis, statin use was associated with a 72% reduction in the risk of tumor inflammation (OR 0.28, P=0.01).

Stacy Loeb, M.D., of Johns Hopkins, summarized findings from a study that examined statin use and tumor characteristics associated with aggressive disease. The study involved 1,282 men who underwent radical prostatectomy from 2003 to 2008 and included 418 patients who reported statin use at the time of surgery.

Statin users had a significantly lower tumor volume, percentage of cancer in the prostatectomy specimen, prevalence of positive surgical margins, and Gleason score of 7 to 10.

Collectively, the findings suggested statin use was associated with more favorable tumor features at prostatectomy.

The remaining studies came from the Mayo Clinic in Rochester, Minn. Rodney Breau, M.D., presented findings from an analysis of 2,427 men who participated in an observational study of prostate cancer. The cohort included 618 statin users.

During a median follow-up of 14.1 years, 75 (12.2%) statin users had a prostate biopsy and 30 (4.9%) had a prostate cancer diagnosis. Compared with nonusers, patients who used statins had more than a 60% reduction in the odds ratio for prostate biopsy and prostate cancer diagnosis.

Among patients who had biennial PSA measurements, statin users were 65% less likely to have PSA values that exceeded age-specific thresholds.

Dr. Breau offered two possible interpretations of the results: The effect of statins on PSA values might account for the lower rates of biopsy and prostate cancer diagnosis. Alternatively, statin use may lower the risk of developing prostate cancer.

Jennifer L. St. Sauver, M.D., reviewed data from a study examining the impact of statins and nonsteroidal anti-inflammatory drugs (NSAIDs) on benign urinary conditions, specifically LUTS and BPH. Records for 2,447 men showed 729 were using statins.

Statin users had a 63% reduction in the odds ratio for moderate or severe LUTS (as defined by AUA symptoms score), a 52% reduction in the frequency of reduced urinary flow, and a 57% reduction in the odds ratio for prostatic enlargement. The magnitude of the reductions increased with duration of statin use, said Dr. St. Sauver. Men who reported taking statins and NSAIDs had even greater reductions in the outcomes assessed.

Ajay Nehra, M.D., presented data from an analysis of statin use and erectile dysfunction (ED) in the same 2,447 men, including 2,075 who had complete data on erectile function and use of phosphodiesterase type 5 (PDE-5) inhibitors.

Dr. Nehra and his colleagues excluded men with ED or PDE-5 inhibitor use at baseline, those who had no regular sexual partner, and those who had a history of prostate cancer, leaving 1,480 for the analysis. Of those, 417 were statin users.

The statin users had a significantly higher prevalence of comorbid conditions that could adversely affect sexual function, including diabetes, hypertension, and coronary disease. Additionally, statin users were significantly more likely to be taking NSAIDs, antidepressants, and drugs to treat LUTS or BPH.

After adjustment age, comorbidities, and medication use, men taking statins had a 37% reduction in the hazard ratio for ED (HR 0.63, 95% CI 0.51 to 0.77).

Moreover, the risk of ED was lowest in men who had taken statins for the longest period of time.

Collectively, the presentations reflected the growing body of literature suggesting that statins influence PSA levels and certain aspects of prostate cancer risk, said J. Brantley Thrasher, M.D., of the University of Kansas in Kansas City, who moderated the press briefing.

However, he said, the studies reported to date have not provided enough information to warrant prescribing statins for prostate cancer or other urologic conditions.

Dr. Banez disclosed relationships with AstraZeneca and Veridex. Dr. Nehra disclosed relationships with GlaxoSmithKline , Pfizer, and sanofi-aventis. Dr. Thrasher disclosed a relationship with sanofi-aventis.

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Primary source: American Urological Association

Source reference:
Hamilton RJ et al “Statin medication use and the risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database” AUA 2009; Abstract 1598.

Additional source: American Urological Association

Source reference:
Banez LL et al. “Association between statins, obesity, and prostate tumor inflammatory infiltrate in men undergoing radical prostatectomy” AUA 2009; Abstract 575.

Additional source: American Urological Association

Source reference:
Loeb S et al. “Is statin use associated with prostate cancer aggressiveness?” AUA 2009; Abstract 576.

TORONTO, April 28 — Acrylamide, the suspected carcinogen found in potato chips and french fries, is not associated with an increased risk of lung cancer, Dutch researchers found.

• Explain to interested patients that animal studies raised fears that acrylamide, a compound that arises in some cooked foods, might be a carcinogen.
• Note that this study suggests there is no link to lung cancer in men and a possibly protective association in women.

In male participants in a large case-control study, there was no link between the disease and consumption of foods high in acrylamide, according to Janneke Hogervorst, M.Sc., of Maastricht University, in the Netherlands, and colleagues.

On the other hand, in women, eating more of the compound appeared to be associated with a lower risk of lung cancer, the researchers reported online in the Journal of the National Cancer Institute.

Acrylamide is found in commonly consumed carbohydrate-rich heated foods, such as french fries and potato chips, and is classified as a probable human carcinogen based on results from animal studies.

The evidence on links to human cancers, on the other hand, is mixed, with some studies showing a link and others finding no association.

To clarify the issue in lung cancer, the researchers turned to the Netherlands Cohort Study on Diet and Cancer, which includes 58,279 men and 62,573 women ages 55 through 69.

They estimated intakes of acrylamide-containing foods and risk factors for

cancer using a self-administered questionnaire at baseline in 1986. Those data were combined with acrylamide levels in relevant Dutch foods to assess the total dietary acrylamide intake.

After 13.3 years of follow-up — from Sept. 17, 1986 to Jan. 1, 2000 — there were 2,649 cases of primary and histologically verified lung cancer in the cohort.

For each 10-microgram per day increment of acrylamide intake, the lung cancer hazard ratio for men was 1.03,with a 95% confidence interval from 0.96 to 1.11.

There was also no trend when male participants were divided into quintiles based on acrylamide intake.

For women, the hazard ratio for each 10-microgram per day increment of acrylamide intake was 0.82, with a 95% confidence interval from 0.69 to 0.96, which was statistically significant at P<0.05.

The hazard ratio for lung cancer for the highest quintile of women (median intake of 36.8 micrograms per day) was 0.45, when compared with the lowest quintile (median intake of 9.5 micrograms per day). That trend, too, was significant, at P=0.01.

The researchers said it might be that acrylamide has a hormonal effect on cancer risk, which might explain the contrast between this study and earlier ones showing an increase in postmenopausal endometrial and ovarian cancer.

On the other hand, other factors could also explain the apparent protective effect in women, according to Lorelei Mucci, Sc.D., and Hans-Olov Adami, M.D., Ph.D., both of Harvard School of Public Health.

In an accompanying editorial, they urged caution in interpreting subgroup analyses that are driven by the data rather than a priori hypotheses.

They also said it is hard to rule out chance in such a finding.

“Perhaps the safer conclusion we can make from the Netherlands study is that the findings do not support a positive association between acrylamide intake from diet and risk of lung cancer,” they concluded.

The study was supported by the Dutch Food and Consumer Product Safety Authority and the Dutch Cancer Society. The researchers reported no conflicts.

Primary source: Journal of the National Cancer Institute

Source reference:

Hogervorst JGF, et al “Lung cancer risk in relation to dietary acrylamide intake” J Natl Cancer Inst 2009; 101: 651-662.

Additional source: Journal of the National Cancer Institute

Source reference:

Mucci LA, Adami, HO “The plight of the potato: Is dietary acrylamide a risk factor for human cancer?” J Natl Cancer Inst 2009; 101: 618-21.