AUA 2024: State-of-the-Art Lecture: Prostate Cancer Screening in High-risk Groups

(UroToday.com) The 2024 American Urological Association (AUA) annual meeting featured a plenary session, and a State-of-the-Art lecture by Dr. Yaw Nyame discussing prostate cancer screening in high risk groups. Dr. Nyame started his presentation by highlighting that prostate cancer will be the #1 malignancy diagnosed in males in the United States in 2024 (299,010 cases, 29%), as well as the #2 cause of cancer related death among males (35,250 cases, 11%) behind only lung cancer. However, when we assess prostate cancer incidence by race (2016-2020), prostate cancer is detected at a 50%-80% higher rate among Black Americans¹:

Moreover, in work presented at the AUA 2024 annual meeting by Frimpong et al, the excess death and life years lost among Black Americans secondary to prostate cancer is 1.51 million life years lost:

Dr. Nyame notes that the average lifetime risk of prostate cancer is ~1 in 8, however, GWAS (common SNPs in the population) each have a small addictive effect on risk (<1.5x). Although a BRCA2 mutation is rare, a mutation on its own leads to a markedly increased risk (5-9x) of prostate cancer. Based on the seminal work from Pritchard et al² in 2016, we also know that rare variants increase the risk of prostate cancer:

This study showed that 82/692 (11.8%) metastatic prostate cancer patients had a deleterious germline mutation in 16 DNA repair genes.

So, what is the definition of a high risk population? Dr. Nyame states that one definition is “Any of the (putative) major groupings of mankind, usually defined in terms of distinct physical features or shared ethnicity.” High risk patients have an earlier onset cancer, higher onset, higher progression, and higher mortality compared to the general population:

Does different natural history affect screening results? Previous work from Gulati et al³ assessed types of increased prostate cancer risk and implications of targeting screening using computer simulation of subgroups with average and hypothetical increased risk of onset of latent disease, progression, and/or cancer-specific death. The simulation implied PSA screening can save more lives among subgroups with increased risk than with average risk, but more intensive screening did not always improve harm-benefit trade-offs. Their analysis suggests screening BRCA2 mutation carriers earlier and more frequently than the average-risk population, but a lower PSA threshold for biopsy is unlikely to improve outcomes.

With regard to the USPSTF recommendations for high risk populations, the following statements are made:

1. Advising African American men: Although it is possible that screening may offer greater benefits for African American men compared with the general population, currently, there is no direct evidence that demonstrates this is true
2. Advising men with a family history of prostate cancer: Although it is possible that screening may offer additional potential benefits for these men compared with the general population, screening also has the potential to increase exposure to potential harms, especially among men with relatives whose cancer was over diagnosed

Dr. Nyame notes that Roman Gulati and Dr. Ruth Etzioni have been instrumental in developing models that estimate the rate of transitioning between states so that the projected incidence under screening matches the observed incidence in SEER:

In 2017, their group estimated three independently developed models of prostate cancer natural history in black men and in the general population using an updated reconstruction of PSA screening, based on the National Health Interview Survey (2005), and on prostate cancer incidence data from SEER (1975-2000).⁴ They found that 30%-43% of black men develop preclinical prostate cancer by age 85 years, a risk that is 28%-56% higher than that in the general population. Among these men, black men had a similar risk of diagnosis (range, 35%-49%) compared with the general population (32%-44%), but their risk of progression to metastatic disease at diagnosis was 44%-75% higher than the general population:

In 2021, Dr. Nyame and colleagues assessed the estimated benefit and harm of intensified PSA screening in Black men.⁵ Two microsimulation models showed that Black men had similar mean lead time to men of all races and similar mortality reduction (21%-24% vs 20%-24%) but a higher frequency of overdiagnosis (75-86 vs 58-60 per 1000 men). Screening Black men aged 40-84 years annually would increase both mortality reduction (29%-31%) and overdiagnosis (112-129 per 1000). However, restricting screening to ages 45-69 years would still achieve mortality reduction (26%-29%) with lower overdiagnosis (51-61 per 1000). Thus, Dr. Nyame states that annual prostate cancer screening should be considered from age 40-69 years among healthy Black Americans.

Equitable and pragmatic screening must also focus on harm reduction. Lives saved by screening are a result of lead time: starting screening earlier, screening more frequently, using biomarkers, and using diagnostic imaging. Several keys to reducing harm in prostate cancer early detection include: (i) age restriction, (ii) reflexive testing (focusing on NPV), (iii) and active surveillance:

Dr. Nyame notes that there are several implementation challenges for appropriately screening high risk populations:

• Primary care provider perspectives
• Structural/social inequities (ie. racism)
• Lack of level 1 evidence in specific populations
• Prostate cancer awareness in high risk populations
• Cost (ie. reflex testing, subsequent treatment, etc)

For the first time in 2023, there is now a PSA screening guideline for Black Americans, organized and sponsored by the Prostate Cancer Foundation (PCF).¹ There are several key questions asked by the PCF panel:

1. Should Black men be screened for prostate cancer?
2. What should Black men know about how screening for prostate cancer is conducted?
3. What information should Black men obtain to make an informed decision about PSA screening and early detection of prostate cancer?
4. At what age should Black men obtain their first PSA test and how often should they be screened for prostate cancer?
5. At what age should Black men consider stopping PSA screening?
6. How should family history and genetic risk be taken into consideration when screening Black men for prostate cancer?

The PCF recommendations for these important questions are as follows:

Dr. Nyame concluded his presentation by discussing prostate cancer screening in high risk groups with the following take-home messages:

• How we define high risk populations carries implications for early detection
• PSA testing should start between 40-45 years in healthy high risk populations interested in early detection
• PSA testing should be considered on an annual basis in high risk populations
• Harm reduction must be a focus of early detection in high risk populations
• We need large collaborative efforts to generate level 1 evidence to support early detection interventions and implementation in high risk populations

Presented by: Yaw Nyame, MD, MS, MBA, University of Washington, Seattle, WA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Urological Association (AUA) Annual Meeting, San Antonio, TX, Fri, May 3 – Mon, May 6, 2024.

References:

1. Garraway IP, Carlsson SV, Nyame YA, et al. Prostate Cancer Foundation Screening Guidelines for Black Men in the United States. NEJM Evid 2024;3(5).
2. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375(5):443-453.
3. Gulati R, Cheng HH, Lange PH, et al. Screening men at increased risk of prostate cancer diagnosis: Model estimates of benefits and harms. Cancer Epidemiol Biomarkers Prev. 2017 Feb;26(2):222-227.
4. Tsodikov A, Gulati R, de Carvalho TM, et al. Is prostate cancer different in black men? Answers from 3 natural history models. Cancer. 2017 Jun 15;123(12):2312-2319.
5. Nyame YA, Gulati R, Heijnsdijk EAM, et al. The Impact of Intensifying Prostate Cancer Screening in Black Men: A Model-Based Analysis. J Natl Cancer Inst. 2021 Oct 1;113(10):1336-1342.