A worrying increase in prostate cancer

A recent report from the American Cancer Society (ACS) points to disturbing trends in prostate cancer (CA Cancer J Clin 2023; doi: 10.3322/caac.21763). After 2 decades of decline, the incidence of prostate cancer increased by 3% per year from 2014 to 2019, resulting in an additional 99,000 new cases. About half of them were advanced cancers. Experts say trends in prostate-specific antigen (PSA) testing have contributed to these changes in prostate cancer statistics.

The current rise has been driven by increases of approximately 4.5% per year for regional and remote stage diagnoses that began as early as 2011. Localized stage disease has also begun to increase, although the trend is not not yet statistically significant.

These results are “very concerning,” said the study’s lead author, Rebecca Siegel, MPH, senior scientific director of surveillance research for the ACS. Long-term trends in prostate cancer incidence “are quite erratic, much more so than any other cancer,” she said. Cases increased in the early 1990s due to the widespread adoption of PSA testing in previously unscreened men.

More recently, reported prostate cancer rates have fallen about 40% since 2007, Siegel said. This was thought to reflect changes in the recommendation for PSA testing by the US Preventive Services Task Force (USPSTF). The USPSTF recommended PSA screening for men 75 and older in 2008, and in 2012 against all PSA screening, in part as a result of trial results for cancer of the prostate, lung , colorectal and ovarian (PLCO), which found no difference in the prostate. cancer mortality rates in men who did and did not undergo PSA screening (N Engl J Med 2009; doi: 10.1056/NEJMoa0810696). However, it was later noted that approximately 80% of the men in the no-screening group had in fact had at least one PSA test, calling the results into question (N Engl J Med 2016; doi:10.1056/NEJMc1515131).

In 2018, the USPSTF revised its recommendation, stating that men between the ages of 55 and 69 should make individual decisions about whether to undergo PSA screening for prostate cancer based on discussions with their clinicians about the pros and cons of screening (JAMA 2018; doi: 10.1001/jama.2018.3710).

But Siegel and others say the damage from previous recommendations may have been done.

“We’ve made a lot of progress against prostate cancer, so there’s concern that this is a reversal of that progress,” she said. “Death rates are still decreasing very slowly, but it looks like they are starting to level off. And we have this increase in late-stage diagnoses, which are not as easy to deal with, and the outcomes are not as good. »

It may take several years to see prostate cancer rates fall again, especially considering the potential impact of the COVID-19 pandemic and its disruption to preventative health care, Douglas said. Scherr, MD, chief of the division of urological oncology at Weill Cornell Medicine – NY Presbyterian Hospital, in New York.

“We used to see a lot of low-risk prostate cancers,” he said. “Today, on the contrary, we see a lot of very high-risk prostate cancers in young people and in all age groups. It’s a paradigm shift.

Any increase or decrease in detection is the result of PSA screening and potentially newer techniques for identifying prostate cancers, added Jonathan Epstein, MD, Reinhard Professor of Urological Pathology at Johns University School of Medicine. Hopkins in Baltimore. There are some differences between the guidelines, he said, which contributes to the controversy.

The USPSTF guidelines are aimed at general practitioners, he said, while the American Urological Association advocates that clinicians discuss PSA screening with patients ages 45 to 75. The ACS recommends men over the age of 50 make an informed decision about screening after a conversation with their healthcare provider, Siegel said. Black men should start this conversation earlier, at 45.

In addition, 3T multiparameter MRI now detects some cancers that would not have been detected before, which could lead to an increase in incidence. “But it also does a better job of finding the most aggressive components of cancer, and doesn’t find low-grade cancers as much, like indolent cancers that you potentially don’t want to find,” Epstein said.

PSA IS STILL A GOOD STARTING POINT

PSA is still considered the gold standard as an early diagnosis for prostate cancer, Scherr said. However, he noted, urologists have gotten smarter about how best to use the test. A quarter of patients with newly diagnosed prostate cancers can be placed on active surveillance rather than treatment, thanks to technologies such as multiparametric MRI, which provides clinicians with detailed views of the prostates of those with PSA high to determine if biopsies are needed, and if so, which area of ​​the prostate to sample.

Additional tests aim to improve the specificity of PSA. These include PSA density, which is PSA divided by prostate volume measured by ultrasound; Free PSA, the amount of free floating PSA not bound to other proteins; and the Prostate Health Index (PHI), a PSA-related blood test to help determine the likelihood of detecting prostate cancer with a biopsy. Another blood test, 4K, measures four PSA-related proteins to assess prostate cancer risk.

“There are a lot now on the market,” he said. “Some of them are valuable, some aren’t very helpful, but overall it definitely improved the validity of the PSA.”

Commercially available urine tests also include PCA3, which can help identify genetic markers and elevated PSA, ExoDx Prostate

and SelectMDx, for men with elevated PSAs between 2 and 10 ng/mL — the so-called “grey area” where urologists may not be sure whether or not to do a biopsy, said Christian Pavlovich, MD, professor emeritus Bernard L. Schwartz in urologic oncology at Johns Hopkins University School of Medicine.

“There are tests like these that could be run reflexively,” Pavlovich said. For example, when a PSA test returns to the 4-10 ng/mL or 2.5-10 ng/mL range, labs can reflexively run a PHI or other related test using the same blood sample . Following these results, laboratories could be set up to receive or analyze urine samples from the same patients to study markers of prostate cancer.

“We are looking for markers of aggressive or more advanced disease,” he said. “The PSA will only suggest that there is something wrong with the prostate, whether it is inflammation, benign growth, cancer or infection. This is where imaging, advanced biomarkers in serum, and urine come into play.

So-called “super-sensitive tests” that identify very low PSA levels, such as in patients who have had prostatectomy, are also important, Scherr said. PSA velocity, the rate of change in PSA over time, is useful in determining when a patient may have local recurrence or micrometastatic disease – small collections of tumor cells that spread to another part of the body.

These other tests vary in popularity among urologists, who may ask labs to stock the tests they’re most interested in, Epstein said. “It’s not like a [test] is definitely recommended over others. They are all competing against each other. The National Comprehensive Cancer Network publishes an annual prostate cancer guideline that reviews supplemental testing to PSA, and is a good resource, he said.

GENOMIC BIOMARKER TESTS ON THE HORIZON

A growing area in the field is the evolution of genomic biomarker testing for prostate cancers, Scherr and Pavlovich said. The ACS report highlights this specifically for black men, for whom racial disparity is particularly important in prostate cancer. “Black men benefit more from screening in general and the integration of personalized biomarkers because they are more likely to harbor genomically aggressive cancer, even with low clinical risk disease,” the authors noted. The incidence of prostate cancer is 70% higher in black men than in white men.

“If someone is diagnosed with prostate cancer, we can assess the mutational load of those cancers, and that allows us to place patients in a low, intermediate, or high risk category as to whether their prostate cancer prostate should be treated or not,” Scherr said.

Commercially available tests include Decipher, Oncotype DX and Prolaris.

“We’re not quite ready to say, ‘Take a blood test to look for your genetic predisposition,’ because we don’t know enough about it to say that some people, on that basis, don’t have need to worry about cancer. and others do,” Pavlovich said. “But once cancer is diagnosed, genomic testing can examine the aggressiveness of the cancer itself beyond what our pathologists look at visually and with their special spots.”

The screening itself could also continue to change.

“There are a lot of efforts going on to try to optimize screening, and I have a feeling that there will soon be changes so that men can be tested, and we can act on cancers that can in turn out to be fatal, rather than treating whatever comes back in terms of a moderate PSA level,” Siegel said. “There’s definitely hope on the horizon, but right now we’re in a somewhat difficult situation.”

Karen Blum is a freelance medical and science writer who lives in Owings Mills, Maryland. +Email: [email protected]