PSA velocity may not contribute to prostate cancer screening process

Issue: March 25, 2011

Inclusion of PSA velocity did not significantly improve the predictive accuracy of prostate cancer screening, according to study results.

Researchers from several sites aimed to evaluate the National Comprehensive Cancer Network and American Urological Association guidelines on early detection of prostate cancer. The guidelines recommend biopsy on the basis of high PSA velocity, even when other indications such as an elevated PSA or a positive digital rectal exam are absent.

The researchers created a multivariate model for prostate cancer that included age, PSA, digital rectal exam results, family history and prior biopsy with or without PSA velocity.

The area under the curve was calculated for 5,519 men who had undergone biopsy as part of the Prostate Cancer Prevention Trial. Eligible participants underwent the procedure regardless of clinical indication.

The researchers also sought to determine the number of additional cancers found or unnecessary biopsies conducted. They evaluated the clinical implications of three PSA velocity cut points (0.35, 0.5 and 0.75 ng/mL^-1y^-1), two definitions of low PSA (<4 and <2.5 ng/mL) and negative digital rectal exam.

When PSA velocity was calculated in the model, a modest increase in area under the curve from 0.702 to 0.709 was observed. The predictive accuracy of the model was smaller for patients with Gleason scores of at least 7 and clinically significant cancer that met Epstein criteria.

One in seven men would be biopsied if biopsies were conducted on men with high PSA velocity but no other indication, according to the results.

PSA velocity predicted cancer in men with low PSA and a normal digital rectal exam result. However, selecting different PSA cut points could yield comparable or superior risk stratification, particularly for high-grade or clinically significant cancer. The researchers said biopsies performed in men with normal digital rectal exam results and PSA of less than 4 ng/mL who had a PSA velocity of more than 0.35 ng/mL would lead to the identification of 115 cancers, but at the cost of 433 unnecessary biopsies. A PSA threshold of 2.5 ng/mL would result in 436 unnecessary biopsies but would identify 24 more cancers.

“In other words, the PSA threshold of 2.5 ng/mL has the same specificity as the PSA velocity threshold 0.35 ng/mL^-1y^-1 (87%) but a higher sensitivity (23% vs. 19% for any cancer, 41% vs. 25% for high-grade tumors, 32% vs. 22% for clinically significant disease),” the researchers wrote. “We found no evidence to support the recommendation that men with high PSA velocity should be biopsied in the absence of other indications; this measure should not be included in practice guidelines.”

In an accompanying editorial, Siu-Long Yao, MD, of The Cancer Institute of New Jersey-University of Medicine and Dentistry of New Jersey (UMDNJ), and of Merck Research Laboratories, and Grace L. Lu-Yao, PhD, of the department of medicine at The Cancer Institute of New Jersey-UMDNJ, said: “Because PSA velocity did not enhance outcomes or improve the detection of more aggressive cancers, the authors conclude that PSA velocity did not add predictive accuracy beyond PSA values alone and noted that one would be better off lowering the threshold for biopsy rather than adding PSA velocity as a criterion for biopsy.”

The results from Vickers and colleagues suggest that using PSA velocity may not provide additional useful information when interpreting screening results, they said, noting that the time required to measure PSA velocity and the postponement of follow-up in affected patients may increase anxiety.

The findings by Vickers and colleagues “help us refine and focus our clinical approach, but they also remind us that the use of PSA as a screening tool still leaves much to be desired,” Yao and Lu-Yao wrote.

Vickers AJ. J Natl Cancer Inst. 2011;doi:10.1093/jnci/djr028.

Yao SL. J Natl Cancer Inst. 2011;doi:10.1093/jnci/djr047.

Follow HemOncToday.com on Twitter.