The results of our analysis suggest that PSA screening increased from its introduction in 1989 to a peak in 2008 in men aged ≥45 years of 22% in men 45-74 years, 20% in men 74-84 years, and 9% in men ≥85 years. After which it declined (in men 45-84 years) or remained steady (in men ≥85 years). While apparent incidence of prostate cancer was rising previously, it is clear the introduction of PSA test in 1989, and its use as a screening test, was associated with a dramatic increase in the incidence of prostate cancer, peaking in 1994.
These trends in use of screening PSA were comparable to previous estimates from surveys reporting ranges from 20 - 67% (Supplementary Table 2) as well as estimates based on Medicare data. 15 Recent findings from the New South Wales 45 and Up Study reported PSA screening rates ranging from 41% in males aged 45–49 years through to 60% in those aged 60–69 years. 16
The close association in rise and fall of prostate cancer incidence and PSA testing suggests much of the changes in incidence relate to PSA screening rates. However, some clear deviations from this association between PSA testing and prostate cancer incidence beg explanation. The rise before 1989 may have been caused by increased digital rectal screening and incidental detection of cancer as a consequence of management of BPH, (which prior to the 1990s was largely surgical – initially open prostatectomy, but increasingly replaced by TURP). 17 In the setting of BPH, cancer may be diagnosed preoperatively (in biopsies performed to decide on management) or postoperatively from the resected tissue 18
The rise of PSA testing in the early 1990s was likely the cause of the high biopsy rates and dramatic increases in prostate cancer incidence in this time. However despite further increases in PSA testing in the late 1990s, biopsy rates dropped, as did the apparent incidence of cancer. One potential explanation of this may be the coincident fall in the rates of TURP at this time which may have reduced both biopsies and cancer diagnoses. Additionally, many patients referred to urologists for biopsies following a raised PSA may have not proceeded to have the procedure or further investigations as a result of their comorbidities or general frailty which need to be considered in the context of the long natural history of prostate cancer. A further number of men also may not have proceeded due to concerns when the possible adverse effects of biopsies were explained.
We are unable to explain why the rates of TURP fell. We had hypothesised that increased use of drugs to manage BPH symptoms, may have been responsible. By reducing bladder outflow obstructive symptoms by either targeting prostatic epithelial cells (in the case of Dutasteride) or smooth muscle in the urethra and prostate (in the case of alpha blocker Tamsulosin), fewer patients would have been referred to urologists with lower urinary tract symptoms. However, we found no evidence of this from the pharmaceutical claims (PBS) data, as the main drug used for BPH symptoms at this time, Prazosin, also appears to have decreased in frequency in throughout the 1990s (Supplementary figure 1) .
From 2000-2010, for men aged 45-84 years, changes in biopsy and incidence followed changes in PSA screening. The decrease in PSA testing after 2008, was probably a response to the publication of a U.S. Preventive Services Task Force (USPSTF) statement in 2008, recommending against PSA screening for men aged >75 years, and declaring that there was insufficient evidence for younger men to recommend screening.19 Two major screening trials were published in March 2009 describing unexpectedly small mortality benefit. 20,21 In 2012, a USPSTF guideline update recommended against PSA based screening for prostate cancer in all age groups. Australia observed reductions in PSA testing in men aged 45-74 years after this22,23, and there was increasing recognition of harms from overdiagnosis. 24,25 For men aged ≥85 years, biopsy rates remained steady in line with PSA screening rates after 2000, but prostate cancer incidence decreased, especially after 2008. This may reflect earlier prostate cancer diagnosis in these men through PSA screening at a younger age. 26 Such earlier detection may have resulted in a longer time living with a prostate cancer diagnosis, but given the apparent lack of mortality reduction in this age group, may have not extended lives.
From 2010 to most recent data, for men aged 45-84 years biopsy and incidence trends followed decreases in PSA screening except in men aged over 85 years whose overall PSA testing rates increased. TURP has been replaced by medical treatment to relieve mild symptoms of BPH including Dutasteride and Tamsulosin Dutasteride combination (which was listed in PBS since 2011and was to be prescribed under streamlined authority with treatment to be initiated by a urologist but can be continued by a general practitioner) and various operative procedures which utilize laser to treat more severe BPH 27 and as outlined in Supplementary table 1.
We observed small decreases in prostate cancer mortality rates after about 1996 in age groups other than those ≥85 years. Advocates assert that they may represent the mortality benefits from screening, especially in younger in men 20. However, the reductions began at the peak in incidence, though any beneficial effect from screening and subsequent treatment would have been delayed, by ten or more years. Thus it seems more likely that the mortality reductions are attributable to advances in the treatment of prostate cancer. Some developed countries (including the United States, Canada, and New Zealand) have reported similar changes in incidence. Others, including Switzerland and United Kingdom show slower rises in prostate cancer incidence over this time 28-31 which may be attributable to national differences in urological practice, and health care systems. Both groups of developed countries show similar reductions in mortality, even those that did little screening. This again suggests that mortality changes are due to improved treatment rather than the effects of early detection and screening.
The Australian National Health and Medical Research Council (NHMRC) endorsed Prostate Cancer Foundation of Australia Clinical Practice Guidelines for PSA testing published in late 2015 recommend that men who are considering having a PSA test should be offered evidence-based decision support, including the opportunity to discuss the benefits and harms of PSA testing, before making the decision to be tested. The guidelines recommend that men who are at average risk of prostate cancer who have been informed of the benefits and harms of testing, and who decide to undergo regular testing for prostate cancer, should be offered PSA testing every 2 years from age 50 to 69. Men aged 70 years or older who have been informed of the benefits and harms of testing, and who wish to start or continue regular testing, should be advised that the harms of testing may be greater than the benefits.32 The listing of multiparametric magnetic resonance imaging (mpMRI) on the Medical Benefits Schedule in 2018, means that MRI may now be widely used to triage which men with an elevated PSA undergo prostate biopsy.33 If this results in fewer biopsies in low risk men, then this may lead to fewer overdiagnosed cancers. The mpMRI will also be useful in active surveillance once a diagnosis is made through histopathology. Although mpMRI was included in the Medicare only last year, it was used considerably in private practice to bypass the need of a biopsy and therefore may have contributed to the drop in biopsy rates in the recent years. Analysis of trends in PSA tests, biopsies, incidence and mortality from 2016 onwards will enable assessment of the impact of both the Australian guideline and the MBS listing of MRI.
Our approach has some limitations. Although cancer registries gather high quality data, the reporting processes, (with varying diagnostic criteria used in different laboratories) are always a concern. Even using specific MBS item numbers, Medicare data cannot reliably differentiate between screening and surveillance (both before and after treatment) uses of PSA testing. Screening reasons probably dominate the data in young men, surveillance in the old. The problem of potential multiple observations from the same man do not arise for PSA item 66655 as they can only claim this once a year. However, this is an issue with PSA item 66656 and prostate biopsy items. We were able to obtain data on PSA testing only from 1994 onwards, as this test was not billed as a separate item in Medicare until then, and we could only differentiate screening claims from 2002. However, the PSA test rates were still low at this early stage, and the major increase in rates occurred only subsequently.