Men presenting with advanced prostate cancer that has spread beyond the prostate are increasingly being considered for treatments directed at the prostate itself. On the basis of results for our international series of 106 men, surgery appears reasonably safe in this setting for certain patients.

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 population-based study. Patients and Methods The study cohort comprised all attendees of the Swiss arm of the European Randomized Study of Screening for Prostate Cancer (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 3 ng/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 in 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.

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