Two-Point Rise in PSA Before Diagnosis Identifies Men at High-Risk for Prostate Cancer Death
Rise in PSA should change the standard of practice for men who have been diagnosed with “low-risk” prostate cancer
BOSTON - Physicians and researchers continue to study prostate-specific antigen, or PSA, to establish guidelines on how to most effectively use the biomarker to identify prostate cancer and its aggressiveness. Researchers from Brigham and Women’s Hospital (BWH) are now one step closer to defining how PSA can be used to predict outcomes and identify patients most likely to benefit from aggressive therapies.
Previous research spearheaded at BWH revealed that a two-point increase in PSA the year prior to radical prostatectomy (RP) signaled metastatic disease. Now, BWH researchers have found that men treated with radiation therapy (RT) only – the standard therapy for men categorized with “low-risk” disease – but who also experienced a two-point rise in PSA during the year preceding diagnosis, had a very high death rate from prostate cancer. Therefore, men who experience this rise should be considered for RT and androgen suppression therapy (AST) – the gold standard of treatment for men with high-risk disease – despite apparent low-risk disease, to improve survival. These findings will be published in the July 27, 2005 issue of the Journal of the American Medical Association.
Prostate cancer is the second most common cancer in men and the cause of approximately 30,000 deaths each year in the US. Currently, PSA testing – a simple blood test performed during a routine visit with a primary care physician – helps provide evidence that the disease is present and also indicates how aggressive it is. However, guidelines are only now forming on how to best interpret PSA levels and translate them into recommendations regarding whom to biopsy and what treatment to offer. This study provides additional evidence to support the dictum that it is not the level of PSA but its change over time – specifically a rise of more than two-points in a year – that should prompt physicians to identify the cancer as having already metastasized and therefore recommend more aggressive combination treatments.
“Previous studies have found that PSA testing over time is a reliable indicator of the risk of death from prostate cancer,” said the study’s lead author, Anthony D’Amico, MD, PhD, chief of Genitourinary Radiation Oncology at the BWH and Dana-Farber Cancer Institute and professor of Radiation Oncology at Harvard Medical School. “This research establishes a new paradigm for PSA and takes our understanding of the biomarker to a higher level. Now, physicians planning to treat a man with RT for low-risk disease need to ensure that a two-point rise in PSA did not occur during the year prior to diagnosis. If it had, the RT and AST therapy should be strongly considered to combat the more aggressive cancer that the two-point rise in PSA is indicating.”
D’Amico, who also recommends that PSA be measured at age 35 to establish a baseline (before enlargement of the prostate occurs and confounds the PSA test) assessed whether a PSA rise of more than two ng/ml during the year prior to diagnosis was significantly associated with prostate cancer-specific mortality (PCSM) following RT. Researchers evaluated PSA velocity among 358 men who were treated with RT for localized prostate cancer between 1988 and 2002. The median age of the men at the time of initial therapy was 71 years with a median follow up of four years following RT. Patients had a serum PSA measurement approximately every 12 months and a digital rectal examination prior to diagnosis.
Overall there were 160 PSA recurrences and 79 deaths of which 30 were from prostate cancer. Of the 30 prostate cancer death observed, 28 occurred in men whose PSA rose by more than two points during the year prior to diagnosis.
Researchers found that a PSA velocity of more than two ng/ml per year was significantly associated with a shorter time to PCSM resulting in a 12-fold increase in PCSM compared to men whose PSA velocity was two ng/ml or less. This translated into nearly 20 percent of men dying of prostate cancer within seven years following RT despite low-risk disease.
According to the researchers, the clinical significance of these findings, when considered in conjunction with previous research, is that a PSA rise of more than two points during the year prior to diagnosis indicates the presence of disease that may not be curable with surgery or radiation alone. “These data provide clinicians with evidence to recommend a more aggressive treatment. Typically, RT plus AST was reserved for men with high-risk disease. Now we believe this may be the most appropriate treatment for men with apparent low-risk disease and a PSA level that rose by more than two points during the year prior to diagnosis,” D’Amico concluded.
Please contact BWH Media Relations for more information at (617) 534-1600 or BWHMediaRelations@partners.org.
BWH is a 747-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832 and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives, dedication to educating and training health care professionals, and strength in biomedical research. With $370M in funding and more than 500 research scientists, BWH is an acclaimed leader in clinical, basic and epidemiological investigation - including the landmark Nurses Health Study, Physicians Health Studies, and the Women's Health Initiative. For more information visit www.brighamandwomens.org
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