PSA Found to Be Highly Predictive of Long-Term Risk of Death From Prostate Cancer

Hans G. Lilja, MD, PhD

A population-based natural experiment using a case-control study of Swedish men aged 44 to 50 years showed that prostate-specific antigen (PSA) levels can accurately predict the risk of developing metastasis or death from prostate cancer up to 30 years later. These results will be presented next month at the 47th Annual American Society of Clinical Oncology (ASCO) meeting in Chicago, Illinois.

Often criticized for its tendency toward overtreatment and its overuse in populations that may have limited benefit, new data about PSA screening adds to the existing evidence about its use. In an interview with the lead author, Hans G. Lilja, MD, PhD, told OncLive, “The testing for the PSA in blood remains controversial despite that we actually have level 1 evidence from randomized, prospective trials in Europe [showing] that PSA-based prostate cancer screening can reduce mortality from prostate cancer.”

Lilja, an attending research clinical chemist in the Departments of Laboratory Medicine, Surgery, and Medicine at Memorial Sloan-Kettering Cancer Center in New York City, remarked in a press release, “Doctors have urgently needed an effective PSA-testing strategy that accurately distinguishes men at high risk for prostate cancer who need aggressive monitoring from those at low risk of the disease, who can be safely spared from frequent testing.”

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Lilja and a team of authors analyzed PSA in archived blood samples that were collected as part of the Swedish Malmö Preventive Project. Blood samples were drawn from an unscreened cohort of 12,090 men who provided blood between 1974 and 1986, from 4999 men who provided repeat samples 6 years later, and from an independent cohort of 1167 men who provided blood at age 60.

The researchers then assessed the median PSA levels for men aged 44 to 50 years, 51 to 55 years, and 60 years to determine long-term risk of prostate cancer morbidity and mortality. The results showed that cancer-related deaths occurred in men aged 44 to 50 years who had PSA levels >1.6 ng/ml. The researchers found that intense surveillance of this small group of men with the highest PSA levels (top 10%) could prevent nearly half of all prostate cancer deaths.

If PSA levels remained below the population median as the men aged, the risk of death from metastatic prostate cancer progressively declined. The researchers found that 28% of metastases or deaths from prostate cancer over the next 27 years occurred in men aged 44 to 50 years who had a PSA below the median (0.7 ng/ml). The risk of metastasis or death was only 18% for men aged 51 to 55 years with a PSA less than the median (0.8 ng/ml). At age 60, only 0.5% of metastasis or death occurred in men with a PSA less than the median for that age group (1.1 ng/ml).

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Testing PSA levels in men aged 51 to 55 years and aged 60 years with PSAs below the median was sufficient to determine the risk of future metastasis or prostate cancer-related death decades later. Applying this strategy to screening would mean that half the population of men would need only 3 PSA tests in their lifetime (ie, at ages 45-49, 50-55, and 60).

“Our overall approach in this paper is to look at the men who have little or nothing to benefit from prostate cancer screening because they do not develop any prostate cancer metastases or do not die from prostate cancer,” said Lilja. “So, our overall approach is basically: do no harm.”

These findings, due to be presented in an oral abstract session at the ASCO meeting on Monday, June 6, 2011, could have a significant impact on future prostate cancer screening programs.

Lilja HG, Savage C, Gerdtsson A, et al. Towards a rational strategy for prostate cancer screening based on long-term risk of prostate cancer metastases and death: data from a large, unscreened, population-based cohort followed for up to 30 years. J Clin Oncol. 2011. (suppl; abstract 4512)