Emerging data and advances in prostate cancer screening

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In this 9-minute presentation, Sigrid Carlsson, MD, PhD, MPH, Memorial Sloan-Kettering Cancer Center, New York, New York, reviews groundbreaking advancements in prostate cancer screening and data from the past year.

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Advances in Prostate Cancer Screening: A Year in Review

Presented at the Virtual ADM Tech Global Summit

Introduction

Good morning, everyone. It is always a pleasure to join you at the Virtual ADM Tech Global Summit. Today, I’ll present a year in review on emerging data and advances in prostate cancer screening. Below are my disclosures and funding acknowledgments.

Key Findings from Recent Trials

PSA Screening and Long-Term Impact

Swedish Göteborg-1 Trial
- Demonstrated that regular PSA screening reduces prostate cancer mortality by ~30% over 22 years of follow-up.
- Key Insight: Longer follow-up periods improve the favorability of the number needed to screen and diagnose.
CAP Trial (UK)
- Showed an 8% reduction in prostate cancer mortality at 15 years after a single PSA test.

Digital Rectal Examination (DRE)

Diagnostic Limitations:
- DRE has poor diagnostic value, as confirmed by the German PROBASE trial and a recent systematic review.
Current Role:
- Although not ideal for screening, DRE remains integral to the clinical workup of men with elevated PSA levels.

PSA as a Prognostic Marker

Malmö Trial Findings:
- PSA is the strongest marker for predicting lethal prostate cancer.
- At age 60, a PSA level <1 eliminates the need for further screening due to the low risk of metastatic disease over 25 years.
Rescreening Recommendations:
- Focus on men with PSA levels >2 at age 60 for optimal benefits.

Impact of Screening Guidelines

USPSTF Recommendations:
- Recent declines in prostate cancer mortality rates have plateaued due to reduced PSA screening, emphasizing the need for careful guideline implementation.
Global Challenges:
- Opportunistic screening without structured programs has led to high testing rates, limited benefits, and increased medical harm, including inequities.
- A recent BMJ article highlighted these issues.

Targeted Guidelines for At-Risk Groups

Collaborated with the Prostate Cancer Foundationto recommend:
- Screening initiation between ages 40–45.
- Annual screening for Black men, who face higher risks of incidence, early onset, and mortality.

European Initiatives and Risk Stratification

PRAISE-U Consortium

Led by Professors Håkan Blé and Monique Roobol, co-funded by the EU.
Aims to implement risk-stratified screening trials to address the increasing disease burden and disorganized testing in Europe.

Proposed Screening Algorithm

Steps:
- Baseline PSA → Risk stratification → MRI → Treatment based on risk.
- Incorporates tools like the ERSPC Risk Calculator, which evaluates factors including PSA, MRI, biopsy history, and patient demographics to predict high-grade disease risk.

Emerging Biomarkers and Risk Stratification Tools

New Biomarkers:
- Adjuncts like the 4K score refine risk stratification and guide decisions on MRI and biopsy.
Polygenic Risk Scores:
- Enhance screening for individuals with risk factors, such as African ancestry, family history, or genetic predispositions.

MRI Integration in Screening

Key Findings from Recent Trials:
- MRI enhances the balance between benefits and harms by maintaining detection of clinically significant disease while reducing overdiagnosis and unnecessary biopsies.
- Göteborg-2 Trial: Targeted biopsies based on MRI findings reduced overdiagnosis without compromising the detection of significant disease.
- Oto Trial: Eliminating biopsies for men with negative MRIs cut overdiagnosis by 50%, with minimal risk of interval cancers.

Challenges with MRI

High variability in MRI interpretations due to scanner quality and reader expertise.
Solutions:
- Centralized expert review.
- AI-augmented interpretation to reduce disparities and improve accuracy.

Optimizing Risk Assessment

Combining PSA, 4K Scores, and MRI:
- Improves high-grade disease detection while reducing unnecessary interventions.
- Example:
  - Stockholm-3 Test: Enhanced specificity, reduced biopsies, and maintained significant disease detection.

Active Surveillance for Low-Risk Disease

Current Standard:
- Active surveillance is the preferred care approach for low-risk localized prostate cancer to minimize the harm of overtreatment.
- Screening programs must integrate active surveillance as a cornerstone of care.

Conclusion

The past year has seen significant advances in prostate cancer screening, from biomarker innovations to risk-adapted algorithms and MRI integration. These strides underscore the importance of precision in screening and equity in care delivery. Thank you for your attention, and I look forward to further discussions at this summit.