Genetics of Prostate Cancer (PDQ®) 4/5 —Health Professional Version - National Cancer Institute

Genetics of Prostate Cancer (PDQ®)—Health Professional Version - National Cancer Institute

Genetics of Prostate Cancer (PDQ®)–Health Professional Version

Screening and Prevention Interventions in Familial Prostate Cancer

In This Section

• Background
• Screening
  • Screening in carriers of BRCA pathogenic variants
• Chemoprevention of Prostate Cancer With Finasteride and Dutasteride

Background

Decisions about risk-reducing interventions for patients with an inherited predisposition to prostate cancer, as with any disease, are best guided by randomized controlled clinical trials and knowledge of the underlying natural history of the process. However, existing studies of screening for prostate cancer in high-risk men (men with a positive family history of prostate cancer and African American men) are predominantly based on retrospective case series or retrospective cohort analyses. Because awareness of a positive family history can lead to more frequent work-ups for cancer and result in apparently earlier prostate cancer detection, assessments of disease progression rates and survival after diagnosis are subject to selection, lead time, and length biases. (Refer to the PDQCancer Screening Overview summary for more information.) This section focuses on screening and risk reduction of prostate cancer among men predisposed to the disease; data relevant to screening in high-risk men are primarily extracted from studies performed in the general population.

Screening

Information is limited about the efficacy of commonly available screening tests such as the digital rectal exam (DRE) and serum prostate-specific antigen (PSA) in men genetically predisposed to developing prostate cancer. Furthermore, comparing the results of studies that have examined the efficacy of screening for prostate cancer is difficult because studies vary with regard to the cutoff values chosen for an elevated PSA test. For a given sensitivityand specificity of a screening test, the positive predictive value (PPV) increases as the underlying prevalence of disease rises. Therefore, it is theoretically possible that the PPV and diagnostic yield will be higher for the DRE and for PSA in men with a genetic predisposition than in average-risk populations.[1,2]

Most retrospective analyses of prostate cancer screening cohorts have reported PPV for PSA, with or without DRE, among high-risk men in the range of 23% to 75%.[2-6] Screening strategies (frequency of PSA measurements or inclusion of DRE) and PSA cutoff for biopsy varied among these studies, which may have influenced this range of PPV. Cancer detection rates among high-risk men have been reported to be in the range of 4.75% to 22%.[2,5,6] Most cancers detected were of intermediate Gleason score (5–7), with Gleason scores of 8 or higher being detected in some high-risk men. Overall, there is limited information about the net benefits and harms of screening men at higher risk of prostate cancer. In addition, there is little evidence to support specific screening approaches in prostate cancer families at high risk. Risks and benefits of routine screening in the general population are discussed in the PDQ Prostate Cancer Screening summary. On the basis of the available data, most professional societies and organizations recommend that high-risk men engage in shared decision-making with their health care providers and develop individualized plans for prostate cancer screening based on their risk factors. A summary of prostate cancer screening recommendations for high-risk men by professional organizations is shown in Table 11.

Table 11. Summary of Prostate Cancer Screening Recommendations for High-Risk Men

ENLARGE

Screening Recommendation Source	Population	Test	Age Screening Initiated	Frequency	Comments
DRE = digital rectal exam; NCCN = National Comprehensive Cancer Network; PSA = prostate-specific antigen.
aDRE is recommended in addition to PSA test for men with hypogonadism.
United States Preventive Services Task Force (2012) [7]	N/A	N/A	N/A	N/A	No specific recommendation for high-risk populations (defined as black men and men with a prostate cancer family history).
American College of Physicians (2013) [8]	African American men and men with first-degree relative diagnosed with prostate cancer, especially <65 y	PSA	≥45 y	No clear evidence to establish screening frequency	Counseling includes information about the uncertainties, risks, and potential benefits associated with prostate cancer screening.
				No clear evidence to perform PSA test more frequently than every 4 y
	Men with family history of multiple family members with prostate cancer diagnosed <65 y	PSA	≥40 y
				PSA level >2.5 µg/L may warrant annual screening
American Urological Association (2013) [9]	African American men and men with a strong prostate cancer family history	PSA	>40 to <55 y	Individualized based on personal preferences and informed discussion regarding the uncertainty of benefit and associated harms.
American Cancer Society (2014) [10]	African American men and/or men with a father or brother with prostate cancer diagnosed <65 y	PSA with or without DREa	≥45 y	Frequency depends on PSA level	Counseling consists of a review of the benefits and limitations of testing so that a clinician-assisted, informed decision about testing can be made.
	Men with multiple family members with prostate cancer diagnosed <65 y	PSA with or without DREa	≥40 y	Frequency depends on PSA level
NCCN (2018) [11]	African American men and men with family history of prostate cancer	N/A	N/A	N/A	The panel states that it is reasonable for African American men to begin discussing PSA screening with their providers several years earlier than Caucasian American men and to consider screening at annual intervals rather than every other year.
NCCN (2019) [12]	Men with BRCA1pathogenic variant	Not specified	Consider screening starting at age ≥45 y	Not specified
	Men with BRCA2pathogenic variant	Not specified	≥45 y	Not specified
NCCN (2018) [11]	Men with a personal or family history of high-risk germline pathogenic variants	Baseline PSA; strongly consider baseline DRE	45–75 y	Every 2–4 y if PSA level <1 ng/mL, DRE normal	Additional recommendations for men with a PSA level >3 ng/mL or very suspicious DRE and men older than 75 y. (Refer to page PROSD-2 of the NCCN guidelines for more information.) Referral to a cancer genetics professional is recommended for those with a known or suspected cancer susceptibility gene.[11]
				Every 1–2 y if PSA level 1–3 ng/mL, DRE normal

Level of evidence: 5

Screening in carriers of BRCA pathogenic variants

An international study that focused on prostate cancer screening in carriers of BRCA1/BRCA2 pathogenic variants versus noncarriers reported initial screening results.[13] The study recruited 2,481 men (791 BRCA1 carriers, 531 BRCA1 noncarriers; 731 BRCA2carriers, 428 BRCA2 noncarriers). A total of 199 men (8%) presented with PSA levels higher than 3.0 ng/mL, which was the study PSA cutoff for recommending a biopsy. The overall cancer detection rate was 36.4% (59 prostate cancers diagnosed among 162 biopsies). Prostate cancer by BRCA pathogenic variant status was as follows: BRCA1 carriers (n = 18), BRCA1 noncarriers (n = 10); BRCA2 carriers (n = 24), BRCA2 noncarriers (n = 7). Using published stage and grade criteria for risk classification,[14] intermediate- or high-risk tumors were diagnosed in 11 of 18 BRCA1 carriers (61%), 8 of 10 BRCA1 noncarriers (80%), 17 of 24 BRCA2 carriers (71%), and 3 of 7 BRCA2 noncarriers (43%). The PPV of PSA with a biopsy threshold of 3.0 ng/mL was 48% in carriers of BRCA2 pathogenic variants, 33.3% in BRCA2 noncarriers, 37.5% in BRCA1 carriers, and 23.3% in BRCA1 noncarriers. Ninety-five percent of the men were white; therefore, the results cannot be generalized to all ethnic groups. Follow-up for this study is ongoing.

Level of evidence (screening in carriers of BRCA pathogenic variants): 3

Chemoprevention of Prostate Cancer With Finasteride and Dutasteride

The benefits, harms, and supporting data regarding the use of finasteride and dutasteride for the prevention of prostate cancer in the general population are discussed in the PDQ summary on Prostate Cancer Prevention.

References

1. Sartor O: Early detection of prostate cancer in African-American men with an increased familial risk of disease. J La State Med Soc 148 (4): 179-85, 1996. [PUBMED Abstract]
2. Matikainen MP, Schleutker J, Mörsky P, et al.: Detection of subclinical cancers by prostate-specific antigen screening in asymptomatic men from high-risk prostate cancer families. Clin Cancer Res 5 (6): 1275-9, 1999. [PUBMED Abstract]
3. Catalona WJ, Antenor JA, Roehl KA, et al.: Screening for prostate cancer in high risk populations. J Urol 168 (5): 1980-3; discussion 1983-4, 2002. [PUBMED Abstract]
4. Valeri A, Cormier L, Moineau MP, et al.: Targeted screening for prostate cancer in high risk families: early onset is a significant risk factor for disease in first degree relatives. J Urol 168 (2): 483-7, 2002. [PUBMED Abstract]
5. Narod SA, Dupont A, Cusan L, et al.: The impact of family history on early detection of prostate cancer. Nat Med 1 (2): 99-101, 1995. [PUBMED Abstract]
6. Giri VN, Beebe-Dimmer J, Buyyounouski M, et al.: Prostate cancer risk assessment program: a 10-year update of cancer detection. J Urol 178 (5): 1920-4; discussion 1924, 2007. [PUBMED Abstract]
7. Moyer VA; U.S. Preventive Services Task Force: Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 157 (2): 120-34, 2012. [PUBMED Abstract]
8. Qaseem A, Barry MJ, Denberg TD, et al.: Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 158 (10): 761-9, 2013. [PUBMED Abstract]
9. Carter HB, Albertsen PC, Barry MJ, et al.: Early detection of prostate cancer: AUA Guideline. J Urol 190 (2): 419-26, 2013. [PUBMED Abstract]
10. Smith RA, Manassaram-Baptiste D, Brooks D, et al.: Cancer screening in the United States, 2014: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 64 (1): 30-51, 2014 Jan-Feb. [PUBMED Abstract]
11. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection. Version 2.2018. Fort Washington, Pa: National Comprehensive Cancer Network, 2018. Available online with free registration.Exit Disclaimer Last accessed December 14, 2018.
12. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 2.2019. Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2018. Available online with free registration.Exit Disclaimer Last accessed October 22, 2018.
13. Bancroft EK, Page EC, Castro E, et al.: Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur Urol 66 (3): 489-99, 2014. [PUBMED Abstract]
14. National Collaborating Centre for Cancer (UK): Prostate Cancer: Diagnosis and Treatment. Cardiff, UK: National Collaborating Centre for Cancer, 2008. Available online. Last accessed December 14, 2018.