Prostate Cancer Survival Improved After PSA Introduced in US

28-08-2012 11:34

August 23, 2012 — Overall survival from metastatic prostate cancer has significantly improved since routine screening with the prostate specific antigen (PSA) test was introduced in the United States around 1990, concludes a new analysis.

The finding was published online in the Journal of Urology and is due to be published in print in October (J Urol 2012;188:1164-1169).

The researchers note that previous analyses from US databases have shown that there has been a significant stage migration of prostate cancer since the routine use of PSA to detect and monitor disease activity. In addition, a recent review of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) databases suggested that there has been an improvement in survival from prostate cancer since PSA testing was introduced.

In this new analysis, the researchers used clinical trial data to investigate the same question. They focused on men who were newly diagnosed with metastatic prostate cancer and who were treated with androgen deprivation therapy (ADT) in clinical trials.

Comparing data collected from clinical trails that were carried out before and after PSA testing became widespread, they found that overall survival had increased significantly, particularly among black American men.

"These gains may be at least partially attributable to PSA monitoring," they conclude.

"While not all of these welcome improvements can be attributable strictly to PSA testing, without a doubt it has played a role in extending many lives," senior author Ian Thompson MD, director for the Cancer Therapy and Research Center and professor of urology at the University of Texas Health Science Center at San Antonio, commented in a statement.

There has been a great deal of controversy over the use of the PSA test to screen healthy men for prostate cancer, with a recent guideline from the US Preventive Services Task Force (USPSTF) recommending against routine screening, on the basis of concern that the harms outweigh benefits. However, there has also been a slew of articles pointing to the beneficial impact that PSA screening has had on the disease since it was introduced, including this latest one.

Approached by Medscape Medical News for comment, Timothy Wilt, MD, MPH, said the finding is "of some interest, not really surprising, exploratory and could be due to many factors." Dr. Wilt is professor of medicine at the University of Minnesota Medical School and was an author of the recent USPSTF guidelines recommending against routine PSA screening.

Comparing Data From 3 Trials

Dr. Thompson and colleagues analyzed data collected from 3 clinical trials conducted by the Southwest Oncology Group, which is sponsored by the National Cancer Institute.

All 3 trials were conducted in men with hormone-naive metastatic prostate cancer (total n = 3096) who were treated with androgen deprivation therapy (ADT).

The patient population and eligibility criteria for all 3 studies were comparable, and all patients received similar treatment (ADT), the researchers noted. The way in which patients were followed for disease progression and survival was comparable in all 3 trials, so differences in prognosis were less likely to be due to healthcare, they comment.

Two of the trials were conducted in the pre-PSA era.

Trial S8494, which enrolled men from 1985 to 1987, compared treatment with leuprolide alone to the combination of leuprolide with flutamide. Median overall survival (OS) in this trial was 30 months.

Trial S8894 enrolled men from 1989 to 1994 and investigated the impact of adding flutamide to bilateral orchidectomy. Median OS in this trial was 33 months.

The third trial was conducted after PSA testing was widespread in the United States.

Trial S9346 accrued between 1995 to 2009 and evaluated intermittent vs continuous ADT. (The results from this trial, which favored continuous ADT, were discussed most recently at this year's annual meeting of the American Society of Clinical Oncology.)

The median OS in this trial was 49 months, which is much greater than the 30 months and 33 months seen in the previous 2 trials conducted before PSA testing was widespread. The hazard ratio of 0.70 indicates a 30% decreased risk for death in the more recent trial compared with the 2 older trials (P < .001), the researchers note.

Survival in Black American Men Improved

Further analysis showed that the improvement in survival was greater among black American men.

In both the 2 older trials, the median OS for black men was 27 months, much shorter than the OS of 34 to 35 months seen for men who were not black.

However, in the most recent trial, this racial difference had disappeared, the researchers note. The median OS was 48 months for black men and 49 months for men who were not black.

"We hypothesize that the improvement is based on greater awareness of prostate cancer and improved health-seeking behavior in African-American men," Dr. Thompson commented.

"The disappearance of this disparity is an important advance in the care of men with prostate cancer," the researchers conclude. The current prognosis in black American men is similar to that in other men, they add.

However, they also point out that the incidence of newly diagnosed prostate cancer among black men was some 2- to 3-fold higher than among men who were not black. "A greater effort is needed to eliminate disparities in prostate cancer," they conclude.

Could Be Due to Many Factors

Dr. Wilt told Medscape Medical News that the finding of an improved survival in the more recent trial compared with the older trials could be due to many different factors.

"The authors describe improved survival of men with metastatic prostate cancer who had not previously received hormone therapy and were enrolled in more recent trials (those with metastatic prostate cancer detected after widespread initiation of PSA testing) compared to men enrolled in trials prior to PSA testing," he noted.

"This does not indicate that PSA screening is beneficial," he said, "but it may suggest that monitoring with a PSA test for men with metastatic disease may be associated with improved survival."

Dr. Wilt noted PSA testing has been approved by the FDA for the monitoring of men with known prostate cancer but not for screening (although it is often used for this in practice).

Many other factors could also explain these findings, especially differences in patient and tumor characteristics, Dr. Wilt continued.

He suggested that in the trial conducted after PSA testing had become widespread, it is likely that individuals had less extensive metastatic disease, and thus their clinical course would be better than that of individuals in the earlier trials, even in the absence of PSA monitoring. Essentially this is the author's conclusion, he said: that there was a shift to less extensive disease (ie, a subtle stage shift).

However, he noted, "This tells us nothing about the effectiveness of a test or treatment to cause reduced mortality. Keep in mind that anyone will survive longer from the time they are diagnosed with a disease even without treatment ("improved survival") if the time they are diagnosed is pushed back earlier due to more aggressive testing or earlier detection of smaller tumors (or other disease)."

Additional factors that could explain the finding include improvements in noncancer treatments and possibly cancer chemotherapies that would lead to improved survival (reduced mortality); such factors would not be related to PSA monitoring, Dr. Wilt commented, but he added that the authors themselves acknowledge this.

The analysis was funded by grants from the National Cancer Institute and by AstraZeneca and Merck & Co. Dr. Thompson reports having a financial relationship with CTNet, and 2 coauthors report relationships with pharmaceutical companies (Amgen, Dendreon, Medivation, Millenium, BristolMyers Squibb, Sanofi, Astellas and Tokai). Dr. Wilt has disclosed no relevant financial relationships.