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Incidence of metastatic prostate cancer has increased among older men as PSA screening declines

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December 30, 2016

The incidence of metastatic prostate cancer appears to be rising in men aged 75 years or older, according to results of a SEER analysis published in JAMA Oncology.

This increase may be linked to the U.S. Preventive Services Task Force (USPSTF) 2008 recommendation against routine PSA screenings in men aged 75 years or older and the 2012 recommendation against routine PSA screening regardless of age.

Jim C. Hu

“It’s what most of us would have predicted, although somewhat sooner,” Jim C. Hu, MD, MPH, professor of urologic oncology at Weill Cornell Medicine, said in a press release. “There was a decrease in prostate cancer metastasis and death after the advent of PSA testing. Remove the screening, and the rates of serious disease rise again.”

Hu and colleagues used the SEER database to identify 1.1 million men aged older than 40 years who were diagnosed with prostate cancer between 2004 and 2013.

Researchers used the Cochrane-Armitage and the Jonckheere-Terpstra test to assess temporal variations in cancer characteristics (available from 2010 to 2013). They used SEER Collaborative staging to analyze quarterly data on incidence of metastasis. Men were stratified based on age younger than or older than 75 years.

The proportion of men aged 75 years or older diagnosed with prostate cancer and distant metastases increased from 6.6% (95% CI, 2.2-7) in 2007 to 12% (95% CI, 11.2-12.7) in 2013. Researchers also observed an increase in the proportion of cancers that were intermediate and high grade, from 58.1% (95% CI, 57.2-59) to 72% (95% CI, 71-73).

During the same period, the incidence of distant metastases increased among men aged younger than 75 years from 2.7% (95% CI, 2.5-2.9) to 4% (95% CI, 3.8-4.2). Intermediate- and high-grade prostate cancer presentation rose from 46.3% (95% CI, 45.9-46.9) to 56.4% (95% CI, 55.9-56.9).

Between 2010 and 2013, median PSA at diagnosis increased among men aged 75 years or older from 9 ng/mL (interquartile range [IQR], 5.8-17.3) to 9.7 ng/mL (IQR, 6.2-21), and among men aged younger than 75 years from 6 ng/mL (IQR, 4.6-9.1) to 6.4 ng/mL (IQR, 4.8-10).

“The recommendation against PSA testing came later for younger men,” Hu said. “So, we might need to watch them over time to see the parallel with older men.”

Hu added the results underscore to need to reevaluate PSA screening guidelines.

“The public health message is that after years of decline, the incidence of metastatic disease has gone up,” he said. “And although the PSA test is not perfect, I don’t think people should be told that this test has no value.”

Up to 50% of American men diagnosed with prostate cancer now choose active surveillance rather than surgery, Hu said.

“The implication of our study is that it is important to have the right to choose screening in order to know whether a man may have an aggressive or indolent prostate cancer,” Hu said. “The burden of overtreatment and side effects may no longer be sufficient to recommend against routine screening.”

The findings of Hu and colleagues differ from the results of study conducted by Ahmedin Jemal, DVN, PhD, vice president of surveillance and health services research program at the American Cancer Society, and colleagues. That research included annual assessments of metastatic disease using SEER Summary Stage, which Hu and colleagues called the “most basic staging system used in cancer registries,” noting it was last updated in 2000.

“We used SEER Collaborative Stage, which standardizes across staging systems to improve data quality,” Hu and colleagues write. “We also more granularly assessed quarterly incidence.”

Researchers also noted that although they demonstrated an increase in the incidence of distant metastases at diagnosis in men aged 75 years or older, they did not examine prostate cancer–specific mortality, which requires longer observation before meaningful differences can be discerned.

In a corresponding editor’s note, Charles R. Thomas, MD, professor and chair of the department of radiation medicine at Oregon Health & Science University, and Yu Shyr, PhD, director of the center for quantitative sciences at Vanderbilt University School of Medicine, note that the controversy regarding the impact of PSA testing on outcomes for men diagnosed with cancer has intensified since the two USPSTF recommendations.

“An earlier publication [in JAMA Oncology] by Jemal et al. suggested that distant metastatic disease has not appreciably changed over the period 2012 to 2013,” Thomas and Shyr wrote. “It is possible that these seemingly contradictory results are simply a statistical random variation of incidence that can change over time depending on the frequency of measurement, as well as the variation in staging definition.

“In the case of these two articles, while both analyze SEER data, Summary Staging was used by Jemal et al., while the current article by Hu et al. used Collaborative Staging,” they added. “The impact on mortality from screening is not well defined. Hence, clinicians will need to be cautious in their interpretation of the screening as well as treatment guidelines for the individual patient in front of them.” – by Chuck Gormley

For more information:

Jemal A, et al. JAMA Oncol. 2016;doi:10.1001/jamaoncol.2016.2667.

Disclosure: Weill Cornell Medicine Patient-Centered Comparative Effectiveness Research Program supported this study. Hu reports speakers bureau roles with Intuitive Surgical and Genomic Health. Nguyen reports consultant roles with Ferring and Nanobiotix. Thomas and Shyr report no relevant financial disclosures.