In what is said to be the first study of its kind to date, researchers from the Cleveland Clinic reported at the ASTRO Annual Meeting that they used different endpoints than those usually applied when gauging the utility of the prostate specific antigen (PSA) test. Rather than looking at overall survival, the team compared 10-year rates of metastases and quality-of-life scores in data from pre- and post-PSA patients with prostate cancer in three risk categories.
Within each of the risk groups, the researchers found that patients treated before screening were significantly more likely to have developed metastatic disease within 10 years of treatment compared with those treated after screening became implemented.
Thirteen percent of all patients developed metastases within 10 years, but the metastases-free survival rate was 82 percent in screened patients versus 58 percent in those treated before PSA testing was available.
The Cleveland Clinic team, led byChandana Reddy, MS, a senior bio statistician, suggests that the endpoints researchers have used in most earlier trials, primarily cancer mortality, overlook a major part of the treatment picture.
Retrospective, Studying 1986-1992 & 1993-1996
The retrospective study was based on data from 1,721 prostate cancer patients treated with radiation or surgery before screening was adopted (1986-1992) or after (1993-1996). To assess which patients might benefit most from screening, the men were also classified into high-, intermediate-, or low-risk disease.
There were 575 men in the prescreening group and 1,146 in the screened group, and 10-year survival was evaluated for metastases incidence, considering specific disease characteristics in each individual.
The risk in the pre-screening group was 44% for high-risk cancer, 21% for intermediate risk, and 28% for those in the low-risk group. This compared with 36% in high-risk patients.
After PSA protocols were implemented, however, the metastases-free survival rate was 27% in men in the intermediate-risk category and 37% in low-risk patients. The only factors associated with these differences were screening, age, T-stage, pretreatment PSA values, and biopsy Gleason scores.
“Our study shows that routine screening not only improves the patient's quality of life by identifying cancer before it metastasizes, but also decreases the burden of care for advanced disease that must be provided by the health care system,” she said at a news briefing. “This demonstrates that the PSA test is extremely valuable in catching the disease earlier and allowing men to live more productive lives after treatment.”
Neither the US Preventive Services nor the American Cancer Society recommends routine PSA screening, of course. The US Preventive Services recommends against screening men under age 75 and last March, the ACS issued an update to its guidelines, emphasizing that asymptomatic men with at least a 10-year life expectancy should be informed by their physician about “the uncertainties, risks, and potential benefits” of PSA testing before making a decision,
Men at average risk should receive this information beginning at age 50 years, while men in higher risk groups should receive the information before 50 years, according to the ACS guidelines.
Ms. Reddy told reporters that she believes the ACS “is sitting firmly on the fence” with regard to PSA screening. “It is still widely debated, but our study shows that screening adds longevity,” she said.
Metastatic prostate cancer is incurable, but patients treated in the post-screening era have had a lower level of metastases after 10 years, according to the team's findings.
Anthony D'Amico: Findings Provocative, and in Line with Other New Information
Anthony V. D'Amico, MD, PhD, Professor of Radiation Oncology at Harvard Medical School and Chief of Genitourinary Radiation Oncology at Brigham and Women's Hospital, said the findings reinforce what he and other researchers have recently learned.
“I think the findings are provocative, and they fall in line with some of the concepts that we are now just learning about the utility of prostate cancer screening,” he said in an interview.
“This study was well done and supports what we know: That older men with other health issues may not benefit from screening, but the same does not hold true for younger and healthier men.”
Nonetheless, there seems to be an entrenched attitude that screening is not helpful, and as a result, many physicians and even oncologists have “very strong feelings” against routine screening, he continued.
“What the Cleveland Clinic study has found—a 14% reduction with 10-year follow-up—is just the beginning of what we may find about screening men earlier, perhaps even at 40 years of age. I believe that more evidence will emerge in the future that will show that screening is helpful in subgroups of men, especially younger patients. The truth is that PSA is a better test in younger men because most men of younger age do not have the prostate enlargement we see in older men,” he said.
“This can be a double-win if we can identify and treat younger patients, it may add many more years to their lives than in older men who may have other health issues and not live to see the benefit.”
In a paper published online November 1 in the Journal of Clinical Oncology (DOI:10.1200/JCO.2010.30.5979), Dr. D'Amico and a team of other researchers (first author is E. David Crawford) analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality, published last year in the New England Journal of Medicine (2009:360:1310-1319). That initial paper found no difference in death rates among more than 70,000 men who had been randomly assigned to annual screening or usual care after seven years of follow-up.
In their re-analysis, however, Dr. D'Amico and his colleagues divided men into those with other health issues and otherwise healthy men who had been screened or not. They discovered that annual PSA screening was associated with more frequent diagnosis of less advanced prostate cancer in healthy men, and reduced the risk their risk of dying from prostate cancer by 44%.
There were 164 prostate cancer deaths after 10 years, but significant fewer in healthy men with screening (22) versus healthy men who were not screened (38), suggesting that screening may help men who have no other health issues and with minimal over-treatment, he told OT.
Dr. D'Amico speculated that another reason that earlier studies have found little evidence of improved mortality with PSA screening might be because healthy men have been lumped in with their less healthy counterparts, those who are less likely to be treated aggressively and are therefore more likely to die of prostate cancer.
“What our new analysis indicates is that PSA testing is most likely to be beneficial if used more selectively, in men who are in good health, generally younger, and are treated aggressively.”