Primary Prevention
Screening
Treatment

Refer to the PDQ summaries on Screening for Prostate Cancer; Prevention of Prostate Cancer; and Prostate Cancer Treatment for more information on interventions for sporadic nonfamilial forms of prostate cancer.

As with any disease process, decisions about risk-reducing interventions for patients with an inherited predisposition to prostate cancer are best guided by randomized controlled clinical trials, and by knowledge of the underlying natural history of the process. Unfortunately, little is known about either the natural history or the inherent biologic aggressiveness of familial prostate cancer compared with sporadic forms. Existing studies of the natural history of prostate cancer in men with a positive family history are predominantly based on retrospective case series. 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 PDQ summary on Cancer Screening Overview for more information.

Given the paucity of information on the natural history of prostate cancer in men with a hereditary predisposition, decisions about risk reduction, early detection, and therapy are currently based on the literature used to guide interventions in sporadic prostate cancer, coupled with the best clinical judgment of those responsible for the care of these patients, with the active participation of well-informed high-risk patients.

There are no definitive studies of primary prevention strategies in men with a hereditary risk of prostate cancer. Thus, there are no definitive recommendations that can be offered to these patients to reduce their risk for prostate cancer at the present time.

The recently published Prostate Cancer Prevention Trial (PCPT), a prospective, randomized clinical trial of finasteride versus placebo, demonstrated a 25% reduction in prostate cancer risk among study participants receiving finasteride.[1] Finasteride administration produced statistically similar reductions in prostate cancer risk in family-history–positive (19% decrease) and family-history–negative (26% decrease) subjects. A subsequent PCPT publication suggested that end-of-study biopsies in asymptomatic men with serum prostate-specific antigen (PSA) values consistently lower than 4.0 ng/mL were more likely to detect prostate cancer in men with an affected first-degree relative (19.7%) versus those with a negative family history (14.4%).[1]

Level of Evidence: Iaii

Refer to the PDQ summary on Prevention of Prostate Cancer for a more detailed description of the prevention of prostate cancer in the general population. Information about ongoing prostate cancer prevention clinical trials is available from the NCI Web site.

There is little information about the net benefits and harms of screening men at higher risk of prostate cancer. There is no 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 summary on Screening for Prostate Cancer.

There is limited information about the efficacy of commonly available screening tests such as the digital rectal examination (DRE) or serum PSA in men genetically predisposed to developing prostate cancer. Furthermore, comparing the results of studies examining the efficacy of screening for prostate cancer is difficult; studies vary with regard to the cut-off values chosen for an elevated PSA test. For a given sensitivity and specificity of a screening test, the positive predictive value (PPV [proportion of men with positive tests who have prostate cancer]) 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.[2,3]

Currently, there are only a few case-control studies and no published randomized trials examining screening in men with an increased risk of prostate cancer. A 10-year longitudinal study of serum PSA and DRE every 6 to 12 months in high-risk men aged 40 years and older has been conducted.[4] Two high-risk categories (1,227 men with a family history of prostate cancer and 1,224 African American men) were compared with 15,964 low-risk non–African American men without a family history of prostate cancer. Suspicious screening results were present in 7% of non–African American men with a family history of prostate cancer, 8% of the low-risk African American men, and 20% of African American men with a family history of prostate cancer. The PPV was inversely proportional to age for those who had an abnormal screening test and underwent biopsy. Among men aged 40 to 49 years, the PPV was 50% for non–African American men with a positive family history, 54% for African American men without a family history, and 75% among African American men with a family history, compared with 38%, 49%, and 52%, respectively, among men aged 50 years and older. Of the 16 cancers detected in high-risk men younger than 50 years, 15 were clinically significant, with intermediate Gleason scores (5–7), and three were not confined to the prostate.[4]

One screening study of the relatives of 435 men with prostate cancer measured serum PSA every 12 months for 2 years. Four hundred and forty-two participants were classified into two groups: sporadic, defined as only one first-degree relative with prostate cancer; or familial, with two or more cases of prostate cancer. PSA higher than 4 ng/mL was present in 0.8% in men aged 40 to 49 years, compared with 12.4% of men older than 50 years. No differences in prostate cancer detection rates or elevated PSA levels were found between sporadic and familial groups. Of the ten prostate cancers detected in this study, nine were clinically localized and of intermediate Gleason scores (5–7).[5]

In a Finnish prostate cancer screening study, family history of prostate cancer was obtained in 2,099 prostate cancer patients.[3] This resulted in the identification of 103 prostate cancer families with two or more affected first- or second-degree relatives having at least one living first-degree unaffected male. From those families, 209 of 226 eligible first-degree unaffected asymptomatic males aged 45 to 75 years were enrolled in a study involving a single serum PSA measurement. An elevated PSA (2.6–28.3 mg/L) was identified in 21 (10%) of subjects. Subsequent biopsies revealed prostate adenocarcinoma in seven (3.3%), including one at an advanced stage, and prostatic intraepithelial neoplasia in two (1%). The mean age of PSA-detected cancers was 65.1 years, 7 years younger than the average age of prostate cancer diagnosis in Finland. In men with a family history of early-onset prostate cancer (mean age of diagnosis in the family, <60 years), the frequency of elevated PSAs was 28.6% and subclinical prostate cancer was 14.3%, significantly higher than the 2.3% to 4.5% reported in other PSA screening studies of this type.[6-11] These findings, however, may not be comparable to U.S. studies: prostate screening practices may differ between Finland and the United States, and rates of prior screening in the population studied were not reported.

A large French Canadian study reported findings from 6,390 men older than 45 years who underwent prostate screening consisting of annual serum PSA and DRE followed by transrectal ultrasound imaging if an abnormality was detected. Of these, 1,563 (24.5%) were found to have an abnormal rectal exam (n = 504) or a PSA > 3.0 μg/L (n = 1,261).[11] Twenty-six refused follow-up; of the remaining subjects, 50.5% underwent biopsy following ultrasound examination. Prostate cancer was identified in 264 men, representing 34.0% of those who underwent biopsy and 4.1% of all 6,390 enrolled subjects. The prevalence of screen-detected prostate cancer was highest in men reporting a brother with prostate cancer (10.21%), as opposed to those reporting a father with prostate cancer (4.75%). Overall, in this study, the PPV of a PSA more than 3.0 μg/L was significantly associated with a family history. The PPV was 28.6% in men with a prostate cancer family history and 17.9% in men without an affected first-degree relative. The increase in PPV of PSA was confined to the men with a normal rectal exam.[11]

A PSA screening study of 20,716 asymptomatic men identified by the Finnish population-based registry did not find a higher PPV for men with a family history of one or more first-degree relatives with prostate cancer, compared with controls. Using a PSA cut-off of 4.0 ng/mL, the PPV of an abnormal PSA for the 964 men with a positive family history was 28% versus 31% for the 19,347 men without a family history. The relative risk (RR) of developing prostate cancer among male relatives of men with prostate cancer was modest (RR = 1.3; 95% confidence interval [CI], 0.95–1.71), suggesting that the family history was not a significant prostate cancer risk factor in this study. This unexpected finding might account for the lack of differences seen in the PPV of the PSA test when comparing men with and without a family history of prostate cancer.[12]

An analysis of data from the control arm of the PCPT yielded a prostate cancer risk model that incorporated PSA level, family history of prostate cancer, and DRE results to predict the likelihood that a man undergoing biopsy would have prostate cancer. Men younger than 55 years were not eligible for participation in this study; therefore, the usefulness of this model in the management of young men from prostate cancer families is unknown.[13]

Current recommendations for screening at-risk members of familial or hereditary prostate cancer kindreds are based on expert opinion panels.[14,15] Therefore, the overall summary of evidence related to the efficacy of screening is level 5. There are no randomized studies that address screening at-risk members of familial or hereditary prostate cancer kindreds, and the observational data are contradictory. Refer to the Screening Behaviors section of this summary for more information on factors that influence prostate cancer screening.

Level of Evidence: 5

Various studies have shown better, worse, or similar survival rates after treatment in men with prostate cancer who have a family history of affected first-degree relatives, compared with those who have a negative family history.[16-19] There is extensive literature addressing whether family history of prostate cancer is linked with aggressive tumor behavior and consequently a worse prognosis. The most current longitudinal report suggests that this is not likely the case.[20]

In general, there is insufficient information available to determine whether treatment strategies differ in efficacy for sporadic cases versus familial cases of prostate cancer. Decisions about treating familial cases of cancer are currently guided by information derived from therapeutic studies in the general population of prostate cancer patients. Therefore, no level of evidence is assigned. A detailed discussion of treatment in these patients is found in the PDQ Prostate Cancer treatment summary, and information about ongoing prostate cancer treatment clinical trials is available from the NCI Web site.

Level of Evidence: Not assigned

References

1. Thompson IM, Goodman PJ, Tangen CM, et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 349 (3): 215-24, 2003.  [PUBMED Abstract]
   
   
2. 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]
   
   
3. 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]
   
   
4. 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]
   
   
5. 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]
   
   
6. Auvinen A, Tammela T, Stenman UH, et al.: Screening for prostate cancer using serum prostate-specific antigen: a randomised, population-based pilot study in Finland. Br J Cancer 74 (4): 568-72, 1996.  [PUBMED Abstract]
   
   
7. Labrie F, Dupont A, Suburu R, et al.: Serum prostate specific antigen as pre-screening test for prostate cancer. J Urol 147 (3 Pt 2): 846-51; discussion 851-2, 1992.  [PUBMED Abstract]
   
   
8. Standaert B, Denis L: The European Randomized Study of Screening for Prostate Cancer: an update. Cancer 80 (9): 1830-4, 1997.  [PUBMED Abstract]
   
   
9. Catalona WJ, Smith DS, Ratliff TL, et al.: Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. JAMA 270 (8): 948-54, 1993.  [PUBMED Abstract]
   
   
10. Mettlin C, Murphy GP, Babaian RJ, et al.: The results of a five-year early prostate cancer detection intervention. Investigators of the American Cancer Society National Prostate Cancer Detection Project. Cancer 77 (1): 150-9, 1996.  [PUBMED Abstract]
    
    
11. 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]
    
    
12. Mäkinen T, Tammela TL, Stenman UH, et al.: Family history and prostate cancer screening with prostate-specific antigen. J Clin Oncol 20 (11): 2658-63, 2002.  [PUBMED Abstract]
    
    
13. Thompson IM, Ankerst DP, Chi C, et al.: Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst 98 (8): 529-34, 2006.  [PUBMED Abstract]
    
    
14. Scardino P: Update: NCCN prostate cancer Clinical Practice Guidelines. J Natl Compr Canc Netw 3 (Suppl 1): S29-33, 2005.  [PUBMED Abstract]
    
    
15. National Comprehensive Cancer Network.: NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection. Version 1.2006. National Comprehensive Cancer Network, 2006. Available online. Last accessed March 5, 2007. 
    
    
16. Bauer JJ, Srivastava S, Connelly RR, et al.: Significance of familial history of prostate cancer to traditional prognostic variables, genetic biomarkers, and recurrence after radical prostatectomy. Urology 51 (6): 970-6, 1998.  [PUBMED Abstract]
    
    
17. Bova GS, Partin AW, Isaacs SD, et al.: Biological aggressiveness of hereditary prostate cancer: long-term evaluation following radical prostatectomy. J Urol 160 (3 Pt 1): 660-3, 1998.  [PUBMED Abstract]
    
    
18. Spangler E, Zeigler-Johnson CM, Malkowicz SB, et al.: Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors. Int J Cancer 113 (3): 471-4, 2005.  [PUBMED Abstract]
    
    
19. Kupelian PA, Kupelian VA, Witte JS, et al.: Family history of prostate cancer in patients with localized prostate cancer: an independent predictor of treatment outcome. J Clin Oncol 15 (4): 1478-80, 1997.  [PUBMED Abstract]
    
    
20. Kupelian PA, Reddy CA, Reuther AM, et al.: Aggressiveness of familial prostate cancer. J Clin Oncol 24 (21): 3445-50, 2006.  [PUBMED Abstract]
    
    

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