High-volume referral centers throughout the United States are seeing a consistent decrease in low-grade prostate cancer and an absolute increase in intermediate- and high-risk disease compared with earlier years before the 2012 US Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)–based screening

This finding, presented earlier this year at the European Urology Association annual meeting, has now been published in the World Journal of Urology.

The researchers compared clinical and pathological characteristics of prostate cancer diagnosed before and after 2012. They found that the absolute number of patients with PSA levels more than ten ng/mL had increased by 24%, from 8.5% of the total number of cases diagnosed between 2008 to 2012 to 13.2% of the total number of cases diagnosed between 2012 and 2016.

At the same time, the absolute number of patients with PSA levels more than 20 ng/mL increased by 44%, from 2.4% of all diagnosed prostate cancers before the recommendations to 4.2% of the total after their release (P < .0001).

In the post-screening era (i.e., after 2012), Ahlering and colleagues also document a higher relative proportion as well as greater absolute numbers of prostate cancer with seminal vesicle invasion, lymph node involvement, and positive surgical margins compared with the prescreening era (P < .001).

More than twice as many men (at 7.5%) presented with lymph node involvement after the USPSTF recommendation than they did before it (P < .001), the investigators add.

There was also a corresponding increase in the absolute number and proportion of cases in which men presented with lymph node metastasis after the USPSFT issued its recommendation compared with before (P < .001).

One year after surgery, rates of biochemical recurrence almost tripled to 17.5% in the four years following the USPSTF recommendation compared with the pre-recommendation era.

"Our findings suggest an urgent need to collaboratively design better screening parameters that minimize overtreatment and maximize curative treatment outcomes," Ahlering and colleagues conclude.

Expected Consequences of Reduced Screening

"These findings are consistent with expected consequences of reduced screening: cancers diagnosed at a later point in their natural history [and these cancers] are associated with more advanced characteristics and poorer clinical outcomes despite treatment," said Roman Gulati, MD, Fred Hutchinson Cancer Research Center, Seattle, Washington.

He also noted that findings are consistent with increased uptake of active surveillance, which removes low-risk cancers from the study population.

"The observed shift likely reflects a combination of these two explanations," Gulati suggested.  

Gulati also pointed to a study of his own, which found that the risks for disease progression among untreated prostate cancer contribute to a near doubling in prostate cancer-specific mortality (PCSM).

That study by Gulati and colleagues was based on the three natural history working models developed by the Cancer Intervention and Surveillance Modeling Network (CISNET) prostate cancer working group.

These models projected that between 23% and 34% of men aged 50 to 59 years with GS 2 to 7 cancers and 62% to 80% of men with GS 8 to 10 cancers were likely to die of their disease in the absence of primary treatment.

Investigators then worked out the extent to which radical prostatectomy could reduce these percentages and found that surgery could reduce 18% to 27% of the deaths in the GS 2 to 7 prostate cancer group and 51% to 66% of the deaths in the GS 8 to 10 prostate cancer group.

"These modeling results suggest that, even under meaningful treatment benefit, less favorable tumor characteristics may be associated with substantially worse outcomes," Gulati observed.

No Survival Difference

Asked by Medscape Medical News to comment on the study, Marc Garnick, MD, professor of medicine, Harvard Medical School, Boston, Massachusetts, pointed out that randomized studies that specifically look at PSA-based screening programs have shown no difference in survival with mature follow-up and little to no differences in prostate cancer-specific survival.

"What this study does underscore is the need for continued improvements in better fine-tuning those selected for screening and for identifying men who may potentially benefit from interventions," he said in an email.

Garnick also observed that data from several large randomized trials on the effect of PSA-screening on mortality risk have been disappointing thus far and indicate that there is a demand for more precision in including men potentially likely to benefit from treatment.