Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1) (original) (raw)
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BJU International, 2015
OBJECTIVE: To assess the value of positive family history (FH) as a risk factor for prostate cancer (PCa) incidence and grade among men undergoing organized PSA-screening in a populationbased study. PATIENTS AND METHODS: The study cohort comprised all attendees of the Swiss arm of the ERSPC with systematic PSA-tests every 4 years. Men reporting first-degree relative(s) diagnosed with PCa were considered to have a positive FH. Biopsy was exclusively PSA-triggered with a threshold of 3ng/ml. Primary endpoint was PCa diagnosis. Kaplan-Meier and Cox regression analyses were used. RESULTS: Of 4,932 attendees with a median age of 60.9 (IQR 57.6-65.1) years, 334 (6.8%) reported a positive FH. Median follow-up duration was 11.6 years (IQR 10.3-13.3). Cumulative PCa incidence was 60/334 (18%, positive FH) and 550/4,598 (12%, negative FH) (OR 1.6, 95%CI 1.2-2.2, p=0.001), respectively. In both groups, most PCa diagnosed had a low grade. There were no significant differences of PSA at diagnosis, biopsy Gleason score or Gleason score on pathologic specimen among men who underwent radical prostatectomy between both groups, respectively. On multivariable analysis, age (HR 1.04, 95% CI 1.02-1.06), baseline PSA (HR 1.13 95% CI 1.12-1.14), and FH (HR 1.6, CI 1.24-2.14) were independent predictors for overall PCa incidence (p<0.0001 each). Only baseline PSA (HR 1.14, 95%CI 1.12-1.16, p<0.0001) was an independent predictor of Gleason score 7 PCa on prostate biopsy. The proportion of interval PCa diagnosed in between the screening rounds was non-significantly different. CONCLUSION: Irrespective of the FH status, the current PSA-based screening setting detects the majority of aggressive PCa and missed only a minority of interval cancers with a 4-year screening algorithm. Our results suggest that men with a positive FH are at increased risk for low grade but not aggressive PCa.
American Journal of Cancer Prevention, 2014
Purpose: In REDUCE, dutasteride was associated with a ~5% absolute reduction in the risk of biopsydetected prostate cancer (PCa). Material and methods: We tested the influence of family history on the association between dutasteride and PCa diagnosis and calculated the number needed to treat (NNT) with dutasteride to avoid one PCa diagnosis. The REDUCE trial tested dutasteride 0.5mg/day for PCa risk reduction in men aged 50-75 with a serum PSA of 2.5-10.0ng/mL and a negative biopsy. Among men who underwent >1 on-study biopsy with complete data (n=6,415; 78.1%), the association between dutasteride and PCa risk as a function of PCa and/or breast cancer (BCa) family history was examined using multivariable logistic regression. Absolute risk reduction (ARR) and NNT were calculated. Results: On multivariate analysis, dutasteride was significantly associated with lower PCa risk in men without family history (25% lower; p<0.001), PCa family history only (37% lower; p=0.009), or BCa family history only (38% lower; p=0.04). While dutasteride lowered PCa risk in men with both PCa and BCa family history by 15%, this was not significant (p=0.69), though the number of men was small (n=115). ARRs were 6-9% for men with a PCa and/or BCa family history vs. 5% in men with no family history which translated into NNTs of 11-16 in men with PCa and/or BCa family history vs. 21 for men without family history. Conclusion: Using dutasteride as a model of chemoprevention, therapies targeting individuals with specific family histories may improve the risk-benefit profile. However, future studies are warranted to confirm our findings.
Effects of Prostate-Specific Antigen Testing on Familial Prostate Cancer Risk Estimates
JNCI Journal of the National Cancer Institute, 2010
Data were from the nationwide population-based Prostate Cancer Database Sweden (PCBaSe Sweden), which includes data from the National Prostate Cancer Register, the Swedish Cancer Register, the Register of the Total Population, the Multi-Generation Register, and the Census database. We investigated the relationship of tumor characteristics, time from diagnosis of the index patient (ie, prostate cancer patients in the National Prostate Cancer Register for whom at least one brother and their father could be identified), calendar period, geographic factors, and socioeconomic status to standardized incidence ratios (SIRs) for prostate cancer among 22 511 brothers of 13 975 index patients in PCBaSe Sweden.
Journal of the National Cancer Institute, 2016
Familial prostate cancer risk estimates are inflated by clinically insignificant low-risk cancer, diagnosed after prostate-specific antigen testing. We provide age-specific probabilities of non-low- and high-risk prostate cancer. Fifty-one thousand, eight hundred ninety-seven brothers of 32 807 men with prostate cancer were identified in Prostate Cancer data Base Sweden (PCBaSe). Nelson-Aalen estimates with 95% confidence intervals (CIs) were calculated for cumulative, family history-stratified probabilities of any, non-low- (any of Gleason score ≥ 7, prostate-specific antigen [PSA] ≥ 10 ng/mL, T3-4, N1, and/or M1) and high-risk prostate cancer (Gleason score ≥ 8 and/or T3-4 and/or PSA ≥ 20 ng/mL and/or N1 and/or M1). The population probability of any prostate cancer was 4.8% (95% CI = 4.8% to 4.9%) at age 65 years and 12.9% (95% CI = 12.8% to 12.9%) at age 75 years, of non-low-risk prostate cancer 2.8% (95% CI = 2.7% to 2.8%) at age 65 years and 8.9% (95% CI = 8.8% to 8.9%) at age ...
Assessing Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial
2006
Background: Prostate-specifi c antigen (PSA) testing is the primary method used to diagnose prostate cancer in the United States. Methods to integrate other risk factors associated with prostate cancer into individualized risk prediction are needed. We used prostate biopsy data from men who par ticipated in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer. Methods: We included 5519 men from the placebo group of the PCPT who underwent prostate biopsy, had at least one PSA measurement and a digital rectal examination (DRE) performed during the year before the biopsy, and had at least two PSA measurements performed during the 3 years before the prostate biopsy. Logistic regression was used to model the risk of prostate cancer and high-grade disease associated with age at biopsy, race, family history of prostate cancer, PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations were created from the estimated logistic regression models. All statistical tests were two-sided. Results: A total of 1211 (21.9%) men were diagnosed with prostate cancer by prostate biopsy. Variables that predicted prostate cancer included higher PSA level, positive family history of prostate cancer, and abnormal DRE result, whereas a previous negative prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA velocity contributed independent prognostic information. Higher PSA level, abnormal DRE result, older age at biopsy, and African American race were predictive for high-grade disease (Gleason score ≥ 7) whereas a previous negative prostate biopsy reduced this risk. Conclusions: This predictive model allows an individualized assessment of prostate cancer risk and risk of high-grade disease for men who undergo a prostate biopsy. [J Natl Cancer Inst 2006;98:529 -34] Since the advent of prostate-specifi c antigen (PSA) screening in the late 1980s, approximately 50% of U.S. men have had a PSA test performed regularly ( 1 ) . Early large-scale prostate cancer screening studies used 4.0 ng/mL PSA as a threshold value to prompt a recommendation for prostate biopsy . Subsequent studies suggested that the risk of prostate cancer, as determined 530 ARTICLES
British journal of cancer, 2006
The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age < or =65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45-69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. O...