Complexed PSA Tests Could Avert Needless Prostate Biopsies

A prostate cancer-screening strategy using complexed prostate-specific antigen rather than total PSA would reduce the occurrence of needless biopsies without compromising sensitivity, according to a series of analyses that compared the detection accuracy of various cutoff values of the two biomarkers.

More accurate markers for detecting prostate cancer are needed, given that the current total PSA (tPSA) cutoff value of 4.0 ng/mL (the threshold at which prostate biopsy is recommended) misses the roughly 30% of cancers that occur in men with tPSA levels below that cutoff.

Dr. R. Joseph Babaian, of the University of Texas M.D. Anderson Cancer Center, Houston, and his coinvestigators compared biopsy findings with tPSA and complexed PSA (cPSA) in 467 men. Of that total, cancer was confirmed by biopsy in 147 (31.5%). Men with cancer had a mean age of 64 years, and those without cancer had a mean age of 62 years.

Using the Mann-Whitney U test, the investigators compared the number of men who had and did not have cancer in each tPSA and cPSA range.

They found that among men with tPSA scores in the broad range of 2.5–6.0 ng/mL, the cancer-detection rate was 31.5%. The cancer-detection rate was similarly 32.6% among men with cPSA values in the range of 2.2–5.1 ng/mL (J. Urol. 2006;175:897–901).

They concluded that among men with tPSA in the range of 2.5–6.0 ng/mL, determining biopsy decisions based on a cPSA cutoff value of 2.2 ng/mL—rather than a tPSA level of 2.5 ng/mL—would have eliminated 12% of needless biopsies but missed 2% of cancer cases. Using the same cPSA cutoff among men with tPSA of 2.5–4.0 ng/mL would have spared 20% of the patients unnecessary biopsies.

In a separate analysis involving 2,807 men who participated in a free cancer-detection program at M.D. Anderson, the investigators concluded that using a 2.2- ng/mL cutoff value for cPSA—rather than a tPSA cutoff of 2.5 ng/mL—would save roughly 3% of this population from undergoing unnecessary biopsies, or 32,000 biopsies per 1 million men.

Avoiding unnecessary biopsies would provide a significant money-saving opportunity for the health care industry. “The direct biopsy charges saved would be about $38 million per 1 million men undergoing a PSA test in the United States,” the investigators wrote. They estimated that nationally, $190 million in direct, annual biopsy charges would be saved.

These study results confirm findings from previous investigations suggesting that cPSA might be a better initial diagnostic tool than tPSA, they wrote.

Their analyses, however, were limited by the fact that some participants came from referrals. A population-based study would, they said, provide stronger evidence of cPSA's superior accuracy.

In an editorial comment, Dr. J. Kellogg Parsons of the University of California, San Diego, wrote that “compared to tPSA, cPSA has increased specificity for prostate cancer detection at all clinically relevant sensitivities. Superior specificity decreases the number of false-positive results, which in turn potentially decreases unnecessary biopsies, health care expenditures, and patient anxiety.”

The study was supported by Bayer Diagnostics. Dr. Babaian disclosed a financial interest and/or other relationship with Bayer and AstraZeneca.

A prostate cancer-screening strategy using complexed prostate-specific antigen rather than total PSA would reduce the occurrence of needless biopsies without compromising sensitivity, according to a series of analyses that compared the detection accuracy of various cutoff values of the two biomarkers.

More accurate markers for detecting prostate cancer are needed, given that the current total PSA (tPSA) cutoff value of 4.0 ng/mL (the threshold at which prostate biopsy is recommended) misses the roughly 30% of cancers that occur in men with tPSA levels below that cutoff.

Dr. R. Joseph Babaian, of the University of Texas M.D. Anderson Cancer Center, Houston, and his coinvestigators compared biopsy findings with tPSA and complexed PSA (cPSA) in 467 men. Of that total, cancer was confirmed by biopsy in 147 (31.5%). Men with cancer had a mean age of 64 years, and those without cancer had a mean age of 62 years.

Using the Mann-Whitney U test, the investigators compared the number of men who had and did not have cancer in each tPSA and cPSA range.

They found that among men with tPSA scores in the broad range of 2.5–6.0 ng/mL, the cancer-detection rate was 31.5%. The cancer-detection rate was similarly 32.6% among men with cPSA values in the range of 2.2–5.1 ng/mL (J. Urol. 2006;175:897–901).

They concluded that among men with tPSA in the range of 2.5–6.0 ng/mL, determining biopsy decisions based on a cPSA cutoff value of 2.2 ng/mL—rather than a tPSA level of 2.5 ng/mL—would have eliminated 12% of needless biopsies but missed 2% of cancer cases. Using the same cPSA cutoff among men with tPSA of 2.5–4.0 ng/mL would have spared 20% of the patients unnecessary biopsies.

In a separate analysis involving 2,807 men who participated in a free cancer-detection program at M.D. Anderson, the investigators concluded that using a 2.2- ng/mL cutoff value for cPSA—rather than a tPSA cutoff of 2.5 ng/mL—would save roughly 3% of this population from undergoing unnecessary biopsies, or 32,000 biopsies per 1 million men.

Avoiding unnecessary biopsies would provide a significant money-saving opportunity for the health care industry. “The direct biopsy charges saved would be about $38 million per 1 million men undergoing a PSA test in the United States,” the investigators wrote. They estimated that nationally, $190 million in direct, annual biopsy charges would be saved.

These study results confirm findings from previous investigations suggesting that cPSA might be a better initial diagnostic tool than tPSA, they wrote.

Their analyses, however, were limited by the fact that some participants came from referrals. A population-based study would, they said, provide stronger evidence of cPSA's superior accuracy.

In an editorial comment, Dr. J. Kellogg Parsons of the University of California, San Diego, wrote that “compared to tPSA, cPSA has increased specificity for prostate cancer detection at all clinically relevant sensitivities. Superior specificity decreases the number of false-positive results, which in turn potentially decreases unnecessary biopsies, health care expenditures, and patient anxiety.”

The study was supported by Bayer Diagnostics. Dr. Babaian disclosed a financial interest and/or other relationship with Bayer and AstraZeneca.

A prostate cancer-screening strategy using complexed prostate-specific antigen rather than total PSA would reduce the occurrence of needless biopsies without compromising sensitivity, according to a series of analyses that compared the detection accuracy of various cutoff values of the two biomarkers.

More accurate markers for detecting prostate cancer are needed, given that the current total PSA (tPSA) cutoff value of 4.0 ng/mL (the threshold at which prostate biopsy is recommended) misses the roughly 30% of cancers that occur in men with tPSA levels below that cutoff.

Dr. R. Joseph Babaian, of the University of Texas M.D. Anderson Cancer Center, Houston, and his coinvestigators compared biopsy findings with tPSA and complexed PSA (cPSA) in 467 men. Of that total, cancer was confirmed by biopsy in 147 (31.5%). Men with cancer had a mean age of 64 years, and those without cancer had a mean age of 62 years.

Using the Mann-Whitney U test, the investigators compared the number of men who had and did not have cancer in each tPSA and cPSA range.

They found that among men with tPSA scores in the broad range of 2.5–6.0 ng/mL, the cancer-detection rate was 31.5%. The cancer-detection rate was similarly 32.6% among men with cPSA values in the range of 2.2–5.1 ng/mL (J. Urol. 2006;175:897–901).

They concluded that among men with tPSA in the range of 2.5–6.0 ng/mL, determining biopsy decisions based on a cPSA cutoff value of 2.2 ng/mL—rather than a tPSA level of 2.5 ng/mL—would have eliminated 12% of needless biopsies but missed 2% of cancer cases. Using the same cPSA cutoff among men with tPSA of 2.5–4.0 ng/mL would have spared 20% of the patients unnecessary biopsies.

In a separate analysis involving 2,807 men who participated in a free cancer-detection program at M.D. Anderson, the investigators concluded that using a 2.2- ng/mL cutoff value for cPSA—rather than a tPSA cutoff of 2.5 ng/mL—would save roughly 3% of this population from undergoing unnecessary biopsies, or 32,000 biopsies per 1 million men.

Avoiding unnecessary biopsies would provide a significant money-saving opportunity for the health care industry. “The direct biopsy charges saved would be about $38 million per 1 million men undergoing a PSA test in the United States,” the investigators wrote. They estimated that nationally, $190 million in direct, annual biopsy charges would be saved.

These study results confirm findings from previous investigations suggesting that cPSA might be a better initial diagnostic tool than tPSA, they wrote.

Their analyses, however, were limited by the fact that some participants came from referrals. A population-based study would, they said, provide stronger evidence of cPSA's superior accuracy.

In an editorial comment, Dr. J. Kellogg Parsons of the University of California, San Diego, wrote that “compared to tPSA, cPSA has increased specificity for prostate cancer detection at all clinically relevant sensitivities. Superior specificity decreases the number of false-positive results, which in turn potentially decreases unnecessary biopsies, health care expenditures, and patient anxiety.”

The study was supported by Bayer Diagnostics. Dr. Babaian disclosed a financial interest and/or other relationship with Bayer and AstraZeneca.