A groundbreaking modeling study from researchers at The University of Sydney's Daffodil Centre has provided compelling evidence that regular prostate-specific antigen (PSA) testing can significantly lower the risk of dying from prostate cancer among Australian men. By simulating real-world testing scenarios aligned with national guidelines, the research demonstrates a substantial mortality benefit while highlighting the need to weigh potential harms. This work arrives at a pivotal moment as Australia updates its clinical guidelines to promote more proactive early detection strategies, potentially positioning the country as a leader in prostate cancer screening worldwide.

Prostate cancer remains one of the most common malignancies affecting men in Australia, with around 17,000 new diagnoses each year and a lifetime risk approaching one in six. Early detection through blood-based PSA tests has long been debated due to concerns over overdiagnosis and overtreatment, but this latest analysis offers a clearer picture tailored to the Australian context. Conducted by a team including Michael Caruana, Roman Gulati, and Karen Canfell, the study utilized advanced microsimulation to project outcomes for average-risk men opting for biennial testing from ages 50 to 69.

What is PSA Testing and How Does it Work?

The prostate-specific antigen (PSA) test measures the level of a protein produced by prostate cells in the blood. Elevated PSA levels can indicate prostate cancer, benign prostatic hyperplasia (enlargement of the prostate gland), or prostatitis (inflammation). While not diagnostic on its own, a raised PSA—typically above 3 ng/mL—prompts further investigation via digital rectal examination (DRE), multiparametric MRI (mpMRI), or biopsy.

In practice, the process unfolds step-by-step: a man discusses risks and benefits with his general practitioner (GP), provides a blood sample, receives results within days, and if elevated, undergoes imaging or biopsy. In Australia, Medicare rebates PSA tests for men over 50 who are informed and choose screening, reflecting a shift from earlier cautionary stances. This simple blood draw has transformed prostate cancer management since its introduction in the late 1980s, enabling detection of cancers at localized stages where cure rates exceed 95 percent.

Understanding PSA dynamics is crucial: levels naturally rise with age, but aggressive cancers accelerate this growth. The test's sensitivity detects most clinically significant tumors early, though specificity challenges lead to false positives in 10-15 percent of cases, necessitating refined protocols like MRI-first approaches to minimize unnecessary biopsies.

Behind the Australian Study: Methods and Modeling

The Policy1-Prostate model, calibrated against New South Wales Cancer Registry data from 1980-1984 and validated against major trials like the European Randomized Study of Screening for Prostate Cancer (ERSPC) and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, simulates individual lifecourses for cohorts of Australian men. It incorporates PSA growth trajectories, disease progression hazards, stage-specific survival, and guideline-concordant management pathways.

Researchers modeled two scenarios: no screening versus biennial PSA testing every two years from age 50 to 69 (nine tests total), with biopsies at PSA ≥3 ng/mL. Outcomes tracked lifetime prostate cancer deaths, overdiagnoses (cancers detected that would not have caused symptoms), false positives, and biopsies. Uncertainty was addressed via probabilistic sensitivity analysis, yielding ranges for all metrics. This Australian-specific approach accounts for local incidence patterns, treatment access, and testing behaviors informed by Medicare Benefits Schedule (MBS) data from 1985-2011.

The model's fidelity was tested by replicating observed declines in Australian prostate cancer mortality post-PSA introduction, confirming its reliability for policy evaluation.

Lives Saved: Quantifying the Mortality Benefit

Core to the findings: among 1,000 average-risk Australian men following biennial PSA testing, 36 die from prostate cancer over their lifetimes, versus 50 without testing—a 27.5 percent relative reduction. This translates to 14 deaths averted per 1,000 screened, or a number needed to screen (NNS) of about 71 to prevent one death. During the screening window, diagnoses rise from 94 to 126 per 1,000, reflecting earlier detection.

• Absolute lifetime risk drops from 5.0 percent to 3.6 percent.
• Benefit accrues gradually, with full impact visible after 10-15 years as lead-time allows curative interventions.
• Higher-grade cancers (Gleason score ≥7) show amplified reductions, underscoring value for lethal disease.

Extrapolated nationally, widespread adoption could avert thousands of deaths annually, aligning with observed mortality declines since PSA uptake peaked in the early 2000s.

The Flip Side: Overdiagnosis and Other Harms

No benefit without caveats—the study estimates 30 overdiagnosed cancers per 1,000 men (32 percent of screen-detected cases), all indolent tumors unlikely to progress symptomatically. For every death prevented, two men face unnecessary diagnosis, potentially leading to overtreatment via radical prostatectomy, radiotherapy, or active surveillance.

Additional burdens include 90 false-positive tests per 1,000 (PSA >3 ng/mL without cancer within a year) and 92 biopsies (9.2 percent biopsied). Psychological anxiety from abnormal results affects quality of life, though mitigated by counseling. In Australia, where active surveillance protocols are robust, overtreatment rates have fallen, but biopsy risks like infection (1-2 percent) persist despite antibiotic prophylaxis.

• Overdiagnosis risk highest in older men; model suggests optimal window 50-69.
• Harms concentrated early in screening, benefits long-term.
• Modern adjuncts like mpMRI reduce biopsies by 25-30 percent, improving net balance.

Contextualizing with Global Evidence: ERSPC, PLCO, and Cochrane

The Australian model aligns with ERSPC's 20 percent mortality reduction after 16 years (13 percent at 23 years), where 1,410 screened to prevent one death. PLCO showed no benefit due to contamination. A May 2026 Cochrane review of six trials (800,000 men) confirmed moderate-certainty evidence of two fewer prostate deaths per 1,000 screened, reversing 2013 skepticism.

These trials inform Australia's nuanced stance: informed choice over population screening. For details on the Cochrane analysis, see the STAT News coverage.

Australia's Proactive Guideline Evolution

Building on this evidence, 2025 draft guidelines from Prostate Cancer Foundation of Australia (PCFA) recommend baseline PSA at age 40 for interested men, biennial testing 50-69, and case-by-case for over-70s. High-risk groups (family history, Aboriginal/Torres Strait Islander, African ancestry) start earlier/more frequently. Medicare-funded, GP-led discussions emphasize shared decision-making.

Full technical report available here. This positions Australia ahead globally, potentially halving mortality through optimized detection.

Perspectives from Stakeholders and Higher Education

University researchers like those at Sydney's Daffodil Centre advocate balanced implementation, with Prof. Karen Canfell noting modeling's role in policy. Clinicians stress pre-test counseling; patients report empowerment from data. In higher education, this underscores interdisciplinary impact—biostatisticians, epidemiologists, oncologists collaborate, fostering careers in cancer research.

Challenges include equity: rural/remote access lags, addressed via telehealth. Men's health advocates push awareness campaigns targeting academics over 50.

Future Outlook: Refining Screening with Technology

Emerging tools promise enhancement: PSA isoforms (free/total ratio), 4Kscore, PHI, MRI triage cut overdiagnosis 20-50 percent. AI-driven risk calculators personalize intervals. Trials like Australia's PROBASE explore baseline testing. Long-term, genomic profiling may stratify risk, minimizing harms while maximizing saves.

For men: discuss with GP, consider baseline early. Researchers: models like Policy1 propel evidence-based policy. Australia leads, but vigilance ensures benefits prevail.

Explore the original study in full detail.

Photo by ANNIE HATUANH on Unsplash