Prostate Cancer Mortality Progress Stalls, Prompting Questions About PSA Policies

Serban Negoita, MD, DrPH

An analysis of prostate cancer trends adjusted for delays in reporting by stage of disease showed that incidence of late-stage disease increased from 2010 to 2014 after a decline in prostate-specific antigen (PSA) use. Additionally, previously declining mortality trends have flattened raising concerns among investigators at the Centers for Disease Control and Prevention, National Cancer Institute (NCI), American Cancer Society, and other cancer registry associations.¹

Serban Negoita, MD, DrPH, and study coauthors of “Annual Report to the Nation on the Status of Cancer, Part II: Recent Changes in Prostate Cancer Trends and Disease Characteristics” evaluated contemporary national-level trends, the relationship with PSA testing prevalence, and trends in incidence according to disease characteristics with stage-specific, delay-adjusted rates.

Annual PSA testing rates were derived from self-reported screening captured as part of the National Health Interview Survey (NHIS) conducted in 2000, 2003, 2005, 2008, 2010, 2013, and 2015. For all age groups, overall prostate cancer incidence rates declined approximately 6.5% per year from 2007. However, the incidence of distant-stage disease increased from 2010 to 2014. The incidence of disease according to higher PSA levels or Gleason scores at diagnosis did not increase.

“One of the interesting findings is that after decades of declining mortality, starting in 2013, mortality leveled off,” said Negoita the lead author and branch chief for Data Quality, Analysis, and Interpretation in the Division of Cancer Control and Population Sciences at the NCI in Rockville, Maryland. “Between 2013 and 2016, mortality did not decline further. That is something that we don’t want to see, though. We want to see a decline in mortality,” he said in an interview with Oncology Fellows.

Historically, the use of PSA testing rose very rapidly in the initial years after the FDA approved first approved the test for surveillance of patients with prostate cancer in 1986, with incidence of newly tested men peaking in 1992. The dissemination of PSA testing among men was practically zero in 1987, but by 1992, 24% of men aged 50 years and older had undergone at least 1 test. When PSA testing was initially introduced in the late 1980s, there was a rapid decline in the incidence of distant-stage prostate cancer. From this, it might be anticipated that reduced testing usage may trigger a similarly rapid increase in distant-stage disease. Starting with the 2008 NHIS, the investigators report a modest fall in PSA testing, consistent with other reports. Concomitantly, they observed an increase in distant-stage disease incidence of 4.4 per 100,000 (between 2008 and 2014).

Prostate cancer mortality increased slowly before 1987 (annual percent change [APC], 0.9), but the trend moved upward at a steeper rate after 1987 for all races (APC, 3.0) and white men (APC, 3.1) and after 1988 for black men (APC, 3.2), as shown in the FIGURE. The highest mortality during the observation period (1975-2015) for all races combined was observed in 1993 (39.3 per 100,000). Mortality for black men peaked in 1993 (81.9 per 100,000), 2 years after mortality peaked for white men (36.5 per 100,000).

Figure. US Prostate Cancer Mortality Rates: All Stages

After the peak, a greater decline in mortality was observed in black men (APC, —2.5) compared with white men (APC, –0.7). Between 2001 and 2015, the rate of decline among black men increased to an APC of –4.2. However, after a more sustained fall between 1994 and 1999 (APC, –4.3), the mortality decline slowed among white men (APC, –3.3) and then leveled off after 2013 (APC –0.4 [statistically nonsignificant]).

The rapid increase in PSA testing between 1987 and 1992 coincides with the dramatic increase in prostate cancer incidence during 1988 through 1992 and a slightly delayed sharp decline in distant-stage prostate cancer incidence between 1991 and 1994.

“These findings, together with the flattening of prev - ously declining mortality trends, illustrate a trend of increasing late-stage disease after decreasing PSA screening at the population level,” Negoita and colleagues noted in their report.

In the interview, Negoita emphasized that because of the type of research conducted, the investigators cannot pinpoint the cause of the leveling off but there are factors that might contribute. “There was a change in cancer screening recommendations,” he said.

He is referring to the May 2012 US Preventive Services Task Force (USPSTF) recommendation against PSA—based screening for prostate cancer. The task force gave routine screening a D rating because it found moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.²

The USPSTF revised its recommendation in May 2017, changing the D to a C, indicating that for men aged 55 to 69 years, the decision about whether to be screened for prostate cancer should be an individual one. Clinicians should not screen men who do not express a preference for screening.

The investigators cite multiple factors that might have contributed to a continuing decline in prostate cancer mortality, such as recent trends toward earlier detection and improved treatment of metastatic and castration-resistant disease. Negoita said that in conjunction with incidence data, death rate trends over the next few years can be used to track the role of PSA screening in declining prostate cancer mortality, although these trends may be partially confounded by steady improvements in prostate cancer treatment and by earlier detection of recurrent disease.

The study is part of the larger “Annual Report to the Nation on the Status of Cancer,” which reported that cancer incidence rates fell in men while remaining stable in women. Additionally, there have been significant declines in cancer death rates, but differences between race and ethnic groups remain.³

The findings demonstrate the complexities that accompany treating prostate cancer. “It’s important for fellows to have a conversation with their patient that takes into account the benefits and harms associated with prostate cancer screening,” Negoita said.

References

1. Negoita S, Feuer EJ, Mariotto A, et al. Annual Report to the Nation on the Status of Cancer, part II: recent changes in prostate cancer trends and disease characteristics. Cancer. 2018;124(13):2801-2814. doi: 10.1002/cncr.31549.
2. US Preventive Services Task Force. Archived final recommendation statement—prostate cancer: screening. USPSTF website. uspreventiveservicestaskforce.org/Page/ Document/RecommendationStatementFinal/prostate-cancer-screening. Published December 30, 2013. Accessed August 24, 2018.
3. Cronin K, Lake A, Scott S, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer. 2018;24(13):2785-2800. doi: 10.1002/ cncr.31551.