Advanced Prostate Cancers Still Rising in US

How Long Until a Plateau?

Nick Mulcahy

May 20, 2020

The incidence of advanced prostate cancers in the United States "persistently" increased annually for 5 years after the United States Preventive Services Task Force (USPSTF) controversially advised in 2012 against prostate-specific antigen (PSA) screening in men of all ages, new research indicates.

But a biostatistician not involved with the study said the USPSTF's recommendation is not wholly to blame because "you need 5 to 7 years of lag time at a minimum to influence PSA screening," and suggested that other factors were also at play.

In the new study, Ahmedin Jemal, DVM, PhD, of the American Cancer Society and colleagues report that for the period 2012­–2016 there were yearly statistically significant upticks in the incidence of regional-stage disease (by an absolute 11% per year) and in distant-stage disease (by an absolute 5% per year).

At the same time, there were annual drops in the incidence of localized prostate cancers in men 50 years or older.

The new study is the first to report data out to the end of 2016.

The two trends — the increase in advanced cancers and decrease in early-stage cancers — have been occurring for 10 years, more or less, but with a steady, sharp rise in advanced disease starting in 2010 to 2012, the findings show.

"These data illustrate the trade-off between higher screening rates and more early-stage disease diagnoses (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease," the authors comment.

The study was published online today in the Journal of the National Cancer Institute.

Several previous studies have reported incidence pattern changes following the USPSTF recommendations against PSA screening for men aged 75 or older in 2008 and all men in 2012, but the data went no further than 2015.

"We saw hints of these changes in the past few years and now we have further confirmation," said Ahmad Shabsigh, MD, urologic oncologist at the Ohio State University Comprehensive Cancer Center, who was asked for independent comment.

"What is a surprise is that it's every year," Shabsigh told Medscape Medical News, referring to the advanced cancer incidence increases.

"To see it so clearly in this study is sad," Shabsigh added.

The study period started in 2005, but did not cover the years after 2018, when USPSTF recommendations changed again and advised that screening be "individualized" for men 55 to 69, and that men 70 and over should be excluded.

US cancer registry data, which are the source of the current study, are not yet available to assess the impact of this most recent change.

End in Sight?

There has been a decline in the proportion of men undergoing PSA tests in the US in recent years, the study authors point out.

Routine PSA testing rates among men aged 50 and older declined from 40.6% in 2008 to 38.3% in 2010, and dropped to 31.5% in 2013, a percentage which held again in 2015, per national self-reported survey data.

The study authors say the cause of the rise in advanced cancers is uncertain because of the descriptive nature of their research.

But Andrew Vickers, PhD, a biostatistician at the Memorial Sloan Kettering Cancer Center in New York City, said the rise in advanced cancers and the drop in early-stage cancers reported in the study are "suggestive of a causal relationship" and a "screening effect."

Vickers argues that there were "a whole bunch of trends that came together in the late [2000s] to influence [PSA] screening."

For example, two landmark randomized clinical trials of PSA screening first reported "unfavorable" results in 2009, which is during the period covered in the current study, and dampened enthusiasm for screening.

The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial reported little or no effect on mortality, the primary outcome of the trials.

It would surprise me if we had bottomed out… Andrew Vickers, PhD, biostatistician at MSKCC

Medscape Medical News asked Vickers to speculate on how long the incidence of advanced prostate cancers will continue to rise in the United States.

"It would surprise me if we had bottomed out [and reached peak increases in advanced cancers] or if we had much longer to go," he said. "My prediction is that if nothing were to change we will probably see some further increases in [the incidence of] advanced disease."

What needs to change? Vickers ticked off a list of "golden rules."

  • First, physicians need to get consent for all PSA tests.

  • Second, PSA tests should not be administered to older men "who won't benefit," such as men 75 years and older with comorbidities such as heart disease.

  • Third, PSA testing should be restricted to younger men.

  • Fourth, clinicians need to be more restrictive about biopsy. "It used to be if you had a high PSA, you would get a biopsy," he said, adding that this approach yielded a lot invasive testing in men with low-grade disease. By using additional tests such as the 4Kscore or Prostate Health Index or MRI, clinicians can limit biopsies to men with greater likelihood of a high-grade cancer. Vickers acknowledged conflict of interest on this point, as he is a patent holder of the 4Kscore.

  • Fifth, don't treat men who are very unlikely to benefit, especially men with Gleason grade 6 disease. Use active surveillance for these men, he said. "Using our existing knowledge, I believe we can completely transform the harm-to-benefit ratio of PSA screening. We would drastically reduce overdiagnosis and overtreatment," he stated.

Additionally, Vickers believes that urologists need to educate local internists and general practitioners and acknowledge that screening and subsequent treatment were "done wrong for a long time." At the same time, urologists should make it clear that patients will not be biopsied "unless there is a really good reason to believe that they have a high risk of high-grade disease."

Vickers concluded: "We can reduce the harm and maintain the benefit of screening."

The study was supported by the American Cancer Society. Jemal and Shabsigh have disclosed no relevant financial relationships. Vickers declared that he is a patent holder of the 4Kscore.

Journal of the National Cancer Institute. Published online May 20, 2020. Abstract

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