A Family History of Lethal Prostate Cancer and Risk of Aggressive Prostate Cancer in Patients Undergoing Radical Prostatectomy 1Scientific RepoRts | 5 10544 | DOi 10 1038/srep10544 www nature com/scie[.]
www.nature.com/scientificreports OPEN received: 24 November 2014 accepted: 24 April 2015 Published: 26 June 2015 A Family History of Lethal Prostate Cancer and Risk of Aggressive Prostate Cancer in Patients Undergoing Radical Prostatectomy Omer A. Raheem, Seth A. Cohen, J. Kellogg Parsons, Kerrin L. Palazzi & Christopher J. Kane We investigated whether a family history of lethal prostate cancer (PCa) was associated with highrisk disease or biochemical recurrence in patients undergoing radical prostatectomy A cohort of radical prostatectomy patients was stratified into men with no family history of PCa (NFH); a firstdegree relative with PCa (FH); and those with a first-degree relative who had died of PCa (FHD) Demographic, operative and pathologic outcomes were analyzed Freedom from biochemical recurrence was examined using Kaplan-Meier log rank A multivariate Cox logistic regression analysis was also performed We analyzed 471 men who underwent radical prostatectomy at our institution with known family history The three groups had: 355 patients (75%) in NFH; 97 patients (21%) in FH; and 19 patients (4%) in FHD The prevalence of a Gleason score ≥ 8, higher pathologic T stage, and biochemical recurrence (BCR) rates did not significantly differ between groups On Kaplan-Meier analysis there were no differences in short-term BCR rates (p = 0.212) In this cohort of patients undergoing radical prostatectomy, those with first-degree relatives who died of PCa did not have an increased likelihood of high-risk or aggressive PCa or shorter-term risk of BCR than those who did not Prostate cancer (PCa) risk stratification is critical to help physicians and patients decide whether they require treatment and what treatment might be best Interestingly, family history of PCa, one of the few known risk factors for the disease, is not associated with worse disease at diagnosis or a worse outcome after treatment1,2 However, the lethality of a patient’s family history, that is whether their first-degree relatives died of the disease, may influence the assignment of PCa risk and fear of adverse outcomes in both patients and physicians3–5 Approximately 10% to 20% of patients with localized PCa are reported to present with a positive family history of PCa Although it has been clearly described as a finding more common in younger versus older men, there is still significant controversy about the importance of the presence of a positive family history of PCa with respect to presentation and prognosis At the genetic level, the association of family history and PCa has been established by characterization of single-nucleotide polymorphisms (SNP) associated with PCa and the recent discovery of the HOXB13 G84E variant, a germline mutation, associated with increased risk of hereditary PCa6–9 In addition to understanding the link between prevalence and genetics, it would be informative to understand the Department of Urology, UC San Diego Health System, San Diego, CA, United States Correspondence and requests for materials should be addressed to C.J.K (email: ckane@ucsd.edu) Scientific Reports | 5:10544 | DOI: 10.1038/srep10544 www.nature.com/scientificreports/ No Family History Prostate Cancer (NFH) Family History Prostate Cancer NonLethal (FH) Family History Prostate Cancer Died (FHD) Variables n = 355 (75%) n = 97 (21%) n = 19 (4%) p-value Age ± SD, mean (years) 62 ± 6.7 60 ± 7.4 61 ± 7.6 0.008* 0.041* Race Caucasian 252 (71%) 81 (84%) 16 (17%) 13 (69%) Other 103 (29%) BMI ± SD, mean (Kg/m2) 27.7 ± 4.2 Hypertension 142 (40%) 36 (37%) (26%) 0.454 Hypercholesterolemia 27.5 ± 3.7 (32%) 27.2 ± 4.7 0.831 132 (37%) 32 (33%) (16%) 0.140 Diabetes Mellitus (DM) 29 (8%) (6%) (5%) 0.747 Coronary artery disease 19 (5%) (6%) (11%) 0.625 5α -reductase inhibitor (Proscar/Avodart) 24 (7%) (3%) (5%) 0.397 Pre-operative PSA (ng/mL) (IQR), median 5.9 (4.2–8.6) 5.3 (4.1–6.6) 5.7 (3.7–6.6) Clinical T Stage 0.759 T1a-c 226 (64%) 67 (70%) 12 (67%) T2a-c 120 (34%) 28 (29%) (33%) T3a-b (2%) (1%) ≤ 153 (45%) 55 (59%) (50%) 7 115 (34%) 23 (25%) (39%) 70 (21%) 15 (16%) (11%) Biopsy Gleason Score ≥ 0.094 0.16 D’Amico risk group 0.099 Low risk 143 (40%) 52 (54%) (32%) Intermediate risk 133 (38%) 28 (29%) 10 (53%) High risk 79 (22%) 17 (18%) (16%) Neoadjuvant/Concurrent treatment 21 (6%) (3%) 0.314 Table 1. Patients’ demographic, clinical characteristics and prostate cancer risk stratification among the three groups SD, standard deviation; BMI, body mass index; PSA, prostate specific antigen *statistically significant (p