Like most cancers, improvements in prevention, early detection, and optimal care would lead to reduced mortality rates and increased survival. Unlike some cancers, however, based on current evidence, prevention and early detection strategies for prostate cancer are limited.
While there is some evidence associating risk factors such as diet and high body mass with increased prostate cancer risk, the World Health Organisation’s International Agency for Research on Cancer has not found conclusive evidence of any group one (agent carcinogenic to humans) modifiable cause of prostate cancer.4
Opportunities to systematically detect prostate cancer early are also limited. Historically, there have been two tests for prostate cancer risk in asymptomatic men – the prostate specific antigen (PSA) test and digital rectal examination (DRE). Neither is recommended for screening. Australian clinical practice guidelines published in 2016 advised against DRE performed in primary care and recommended PSA testing only for individual men informed of the associated risks of harm as well as potential benefits.5
To our knowledge, no country with a comparable health system to Australia’s has an organized prostate cancer screening program targeting average-risk men in an identified age cohort. Yet effective earlier detection would be a vital step for reducing prostate cancer death rates. While the pathology is complex, and the lead time from diagnosis to death can be one of the longest in all cancers, five-year prostate cancer survival in Australia ranges from above 90% for localized and regional stage to below 40% for distant stage.3 If more prostate cancers are detected and treated effectively before they reach distant stage, many more lives would be saved.
It might follow, then, that finding more localized (confined to the prostate gland) prostate cancer cases would mean reduced death rates. However, a recent paper published by our group found that, although localized disease rates fell from 1994 to 1998 and from 2008 onward, survival has improved, and death rates have fallen since the 1990s (Figure).3
Figure. Trends in stage-specific prostate cancer incidence rates, overall prostate cancer mortality rates and 5-year relative survival, New South Wales, Australia (sourced from Luo et al 2022).3
The lines represent rates modeled by Joinpoint regression.
These findings are counterintuitive when considered in relation to other prevalent cancers, particularly those that can be detected through screening programs. Stage shift and mortality reduction in breast cancer were factors in the support for mammography screening by WHO’s International Agency for Research on Cancer following a major global review of the evidence in 2015.6
Our analysis shows that age-standardized prostate cancer mortality rates fell by around two thirds from 1995 to 2015, despite a 20% fall in the rate of localized cancers diagnosed over the same period. Incidence of localized disease fell sharply and survival for localized disease remained stable yet overall survival improved markedly.3
The rates of localized disease broadly mirrored rates of PSA testing, which is subsidized in the Australian health system. As PSA testing rates fell, so too did localized disease rates. Yet mortality rates still continued to fall significantly. Therefore, substantial numbers of men who would have been diagnosed with localized disease when PSA testing rates were higher, avoided a localized prostate cancer diagnosis – but they did not die from prostate cancer over the reporting period.3
So, what does it all mean? For one thing, it highlights the complexities of prostate cancer staging and pathology. We can, however, conclude from the findings that major reductions observed in prostate cancer mortality were not associated with increased detection of localized disease due to elevated PSA levels.
The specificity and sensitivity limitations of PSA as a screening tool in relation to mortality benefit are well documented.7 So too are the historically high rates of overdiagnosis, overtreatment and related harms, including adverse outcomes such as erectile dysfunction and urinary incontinence as a result of unnecessary invasive treatment.8,9 Our study has not estimated the number of men in the cohort who were not diagnosed with localized disease due to reduced PSA testing rates, avoided the harms of overtreatment and did not die from prostate cancer. However, these numbers could be obtained from disease models.
Nonetheless, it is important to recognize that PSA remains the only available test for evaluating an asymptomatic individual man’s risk of prostate cancer. On current evidence, the key is conservative use of PSA, for informed individual men who might benefit from the test, supported by evidence-based clinical practice guidelines used by all health disciplines involved in managing prostate cancer risk assessment and follow-up.
Updating the Australian guidelines is long overdue. While their use is effective, new evidence is continually being published. This includes critical areas of triage and referral such as targeted use of multiparametric medical resonance imaging and ensuring optimal care is standard care.
Our study suggests that the drivers of improved prostate cancer mortality outcomes are less likely to relate to the diagnosis of localized versus non-localized disease and more likely to be the result of improved treatment and management of disease at all stages. Reduced rates of localized disease that would not have caused harm in a man’s lifetime may also enable more effective targeting of limited healthcare resources. We need more of what has worked to further reduce prostate cancer mortality and support quality of life for men affected, and men not yet affected, by prostate cancer.
Written by: Paul B. Grogan,1 Qingwei Luo,1 Manish I. Patel,2,3 Dianne L. O’Connell,1,4 David P. Smith1,5,6
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia.
- Specialty of Surgery, University of Sydney, Sydney, New South Wales, Australia.
- Department of Urology, Westmead Hospital, Westmead, Sydney, New South Wales, Australia.
- School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
- Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
- School of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.
- Australian Institute of Health and Welfare (AIHW). Cancer data in Australia. Cat. no: CAN 122. 8 July 2022 ed, 2022.
- Luo Q, O’Connell DL, Yu XQ, et al. Cancer incidence and mortality in Australia from 2020 to 2044 and an exploratory analysis of the potential effect of treatment delays during the COVID-19 pandemic: a statistical modelling study. The Lancet Public Health 2022;7(6):e537-e48. doi: https://doi.org/10.1016/S2468-2667(22)00090-1
- Luo Q, Yu XQ, Kahn C, et al. Changes in prostate cancer incidence, mortality and survival in relation to prostate specific antigen testing in New South Wales, Australia. Cancer Epidemiol 2022;78:102159. doi: https://doi.org/10.1016/j.canep.2022.102159
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Personal Habits and Indoor Combustions. Vol 100 – A Review of Human Carcinogens. Part E. Lyon (FRC): World Health Organisation, 2012.
- Prostate Cancer Foundation of Australia and Cancer Council Australia PSA Testing Guidelines Expert Advisory Panel. Clinical practice guidelines PSA Testing and Early Management of Test-Detected Prostate Cancer. Sydney: Cancer Council Australia, 2016.
- IARC Working Group on the Evaluation of Cancer-Preventive Strategies. Breast Cancer Screening, IARC Handbooks of Cancer Prevention Volume 15. Lyon, France: International Agency for Research on Cancer 2016.
- Wolf AM, Wender RC, Etzioni RB, et al. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin 2010;60(2):70-98. doi: 10.3322/caac.20066 [published Online First: 2010/03/05]
- Loeb S, Bjurlin MA, Nicholson J, et al. Overdiagnosis and overtreatment of prostate cancer. European urology 2014;65(6):1046-55. doi: 10.1016/j.eururo.2013.12.062 [published Online First: 2014/01/09]
- Albertsen PC. Prostate cancer screening and treatment: where have we come from and where are we going? BJU Int 2020;126(2):218-24. doi: 10.1111/bju.15153 [published Online First: 2020/07/28]
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