More older men with prostate cancer (75 years or older) are now presenting with distant metastases at the time of diagnosis, the first national population-based study indicates.
The new findings suggest that the 2008 recommendation against prostate-specific antigen (PSA) screening for this age group from the US Preventive Services Task Force (USPSTF) is changing the way prostate cancer presents.
"It's what most of us would have predicted, although somewhat sooner," lead author Jim Hu, MD, MPH, Weill Cornell Medicine-New York Presbyterian Hospital, New York City, said in a statement.
"There was a decrease in prostate cancer metastases and death after the advent of PSA testing. Remove the screening and the rates of serious disease rise again," he added.
The new study is reported in a research letter published onlineDecember 29 in JAMA Oncology.
Dr. Hu and colleagues identified 545,399 men (aged 40 years or older) who had been diagnosed with prostate cancer between 2004 and 2013. (Editor's note — this number is different from what is in the published paper, but it is correct, as confirmed by Dr Hu.)
The incidence of distant metastasis was derived quarterly by using the Surveillance, Epidemiology, and End Results (SEER) Collaborative staging.
The proportion of men under age 75 who presented with distant metastases rose from 2.7% in 2004 to 4% in 2013; the difference was not statistically significant.
However, the proportion of men in the same age group who presented with Gleason grade 7 or Gleason grade 8 to 10 prostate cancer rose from 46.3% in 2004 to 56.4% in 2013, a significant difference (P < .01), they add.
"Similarly, in men 75 years or older, there was an increase in the proportion of distant metastases from 6.6% [in 2004] to 12.0% [in 2013] (P < .01)," the researchers state.
Furthermore, rates of intermediate and high-grade prostate cancer in older men rose from 58.1% in 2004 to 72% in 2013 (P < .01), they add.
PSA values were available for 2010 to 2013. On the basis of values from these years only, median PSA values increased from 6.0 ng/mL in 2010 to 6.4 ng/mL in 2013 among younger men and from 9.0 ng/mL in 2010 to 9.7 ng/mL in 2013 in men 75 years of age and older.
"In adjusted analysis…the incidence of distant metastases at diagnosis in men 75 years or older decreased from 2004 to 2011 and increased afterward," Dr. Hu and colleagues write, "[whereas] no change was observed in men younger than 75 years."
The study authors suggest that the lack of any increase in distant metastases observed in younger men during the study interval might reflect the timing of the recommendations from the USPSTF, which in 2012 extended their recommendation not to offer routine PSA testing to men of any age.
As Dr Hu explained to Medscape Medical News, it's been estimated that PSA screening leads to earlier detection of prostate cancer by approximately 6 years.
"It would [therefore] be a few more years before we see an increased incidence of prostate cancer metastases in younger men in the US," he predicted. He added that he hoped this possibility will be widely recognized so that the incidence of metastatic, incurable prostate cancer will not increase.
Although Dr Hu and colleagues found no effect in men younger than 75 years, another recent study did. In an earlier research letter also published in JAMA Oncology. Ahmedin Jemal, DVM, PhD and colleagues from the American Cancer Society reported that incidence of early-stage prostate cancer decreased between 2011 and 2012 in men 50 years of age and older and that this decline persisted through to 2013.
The decline in early-stage disease reflects the decline in PSA screening recommended by the USPSTF, those authors asserted.
"Whether this pattern will lead to a future increase in the diagnosis of distant-stage disease and prostate cancer mortality requires long-term monitoring because of the slow-growing nature of this malignant neoplasm," Dr Jemal and colleagues concluded.
However, as Dr Hu countered, the difference between Jemal and coauthors' study and their own is that Hu et al used a more sophisticated staging system within SEER.
"We also assessed the quarterly incidence [of distant metastases], whereas their study was annual," Dr Hu added.
In point of fact, investigators from both studies used SEER data, and both demonstrated a statistically significant increase in distant metastases at the time of diagnosis in men 75 years of age and older in 2013 compared with rates in 2011, Dr Hu noted.
"Ultimately, our research supports PSA screening in terms of determining whether a man has prostate cancer and, if so, whether it is indolent and may be monitored through active surveillance or treated more aggressively," he concluded.
Asked by Medscape Medical News to comment on the current findings, Marc Garnick, MD, professor of medicine, Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, Massachusetts, noted that since the USPSTF provided a D recommendation for PSA testing regardless of age, race, or family history, one would have expected a relative increase in higher-grade Gleason scores and more advanced disease because men would likely seek medical care as a result of clinical symptoms.
"This was seen in the over 75 years of age population [in the study by Hu et al], where the number of patients evaluated clearly decreased, accompanied by an increase in Gleason 8 to 10, T3 to T4 and metastatic disease," Dr Garnick elaborated in an email.
"In contrast," he added, "in those under the age of 75, the number of patients evaluated were relatively stable."
However, as Dr Garnick pointed out, data from the Hu et al analysis do not indicate whether the men who were diagnosed with adverse-feature prostate cancer represented a screened population or a clinically detected population; such information would have been helpful.
"The clinical implications of the data presented by Hu et al cannot yet be interpreted," Dr Garnick concluded.
"In the end, there are now numerous randomized, prospective controlled studies — some with follow-up approaching 15 years — that despite investigators' strongest desires to show a survival benefit to PSA-based screening, have all come up empty-handed, the most recent ProtecT evaluation notwithstanding," he added.
"The true meaning of the data presented by Hu et al may need at least a decade more of maturing before any conclusions can be drawn," Dr Garnick said.
The Prostate Testing for Cancer and Treatment (ProtecT) trial recruited men 50 to 69 years of age in the United Kingdom. Men diagnosed with localized prostate cancer based on PSA screening were randomly assigned to active surveillance, radical prostatectomy, or radiotherapy, as previously reported by Medscape Medical News.
At a median of 10 years of follow-up, only about 1% of men in any of the 3 assigned groups had died. All-cause mortality in the 3 treatment groups was also low at about 10%.
On the other hand, men assigned to either of 2 active therapy groups were less than half as likely to progress over the 10-year follow-up as men in the active surveillance group (P < .001), and the rate of metastatic disease was also about half that in the active treatment groups compared with the active surveillance group (P = .004).
The ProtecT investigators concluded that it's too soon to tell where active treatment results in better disease-specific or all-cause mortality compared with active surveillance.
This study was supported by Weill Cornell Medicine Patient-Centered Comparative Effectiveness Research Program. Dr Hu reported being on the speakers' bureau for Intuitive Surgical and Genomic Health, and coinvestigator Dr Nguyen reported consulting for Ferring and Nanobiotix. The study authors have disclosed no other relevant financial relationships. Dr Garnick is editor-in-chief of the Harvard Medical School annual report on prostate disease and website.
JAMA Oncol. Published online December 29, 2016. Abstract