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Article of the Week: FH as a risk factor for PCa

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

A positive family history as a risk factor for prostate cancer in a population-based study with organised prostate-specific antigen screening: results of the Swiss European Randomised Study of Screening for Prostate Cancer (ERSPC, Aarau)

Marco Randazzo*,, Alexander Muller*, Sigrid Carlsson, Daniel Eberli*, Andreas

 

Huber, Rainer Grobholz**, Lukas Manka††, Ashkan Mortezavi*, Tullio Sulser*, Franz Recker† and Maciej Kwiatkowski,††

 

*Department of Urology, University Hospital Zurich, Zurich, Department of Urology, Cantonal Hospital Aarau, Aarau, Switzerland, Department of Surgery (Urology Service), Memorial Sloan Kettering Cancer Center, New York, NY, USA, §Department of Urology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, Department of Laboratory Medicine, **Department of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland, and ††Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany

 

Objective

To assess the value of a positive family history (FH) as a risk factor for prostate cancer incidence and grade among men undergoing organised prostate-specific antigen (PSA) screening in a population-based study.

Subjects and Methods

The study cohort comprised all attendees of the Swiss arm of the European Randomised Study of Screening for Prostate Cancer (ERSPC) with systematic PSA level tests every 4 years. Men reporting first-degree relative(s) diagnosed with prostate cancer were considered to have a positive FH. Biopsy was exclusively PSA triggered at a PSA level threshold of 3 ng/mL. The primary endpoint was prostate cancer diagnosis. Kaplan–Meier and Cox regression analyses were used.

Results

Of 4 932 attendees with a median (interquartile range, IQR) age of 60.9 (57.6–65.1) years, 334 (6.8%) reported a positive FH. The median (IQR) follow-up duration was 11.6 (10.3–13.3) years. Cumulative prostate cancer incidence was 60/334 (18%, positive FH) and 550/4 598 (12%, negative FH) [odds ratio 1.6, 95% confidence interval (CI) 1.2–2.2, P = 0.001). In both groups, most prostate cancer diagnosed was low grade. There were no significant differences in PSA level at diagnosis, biopsy Gleason score or Gleason score on pathological specimen among men who underwent radical prostatectomy between both groups. On multivariable analysis, age (hazard ratio [HR] 1.04, 95% CI 1.02–1.06), baseline PSA level (HR 1.13, 95% CI 1.12–1.14), and FH (HR 1.6, 95% CI 1.24–2.14) were independent predictors for overall prostate cancer incidence (all P < 0.001). Only baseline PSA level (HR 1.14, 95% CI 1.12–1.16, P < 0.001) was an independent predictor of Gleason score ≥7 prostate cancer on prostate biopsy. The proportion of interval prostate cancer diagnosed in-between the screening rounds was not significantly different.

AOTW4Apr

Conclusion

Irrespective of the FH status, the current PSA-based screening setting detects the majority of aggressive prostate cancers 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 of low-grade but not aggressive prostate cancer.

Editorial: To PSA or not to PSA?

Family history (FH) has long been known to increase a man’s risk of developing prostate cancer (PCa); there is an approximately twofold increased risk with an affected father and a threefold increased risk with an affected brother [1]. Furthermore, FH may increase the risk of more aggressive disease for family members, although results of studies in the PSA screening era have been inconsistent [2, 3]. Using FH as a risk factor, the present analysis of the Swiss arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) conducted by Randazzo et al. [4] sought to determine whether men with a positive FH of PCa, followed up by PSA screening every 4 years, would have a higher risk of having more aggressive disease.

As expected, the present results show that a significantly higher proportion of men with a FH were diagnosed with PCa compared with those with a negative FH; however, there was no difference in the frequency of more aggressive disease amongst men with a FH, therefore, while FH information can be used to identify men at highest risk of PCa, it does not appear to identify those who are most likely to harbour clinically significant disease.

One reason that a positive FH may not be associated with aggressiveness in the present study is that it has been previously established that PSA screening is associated with a migration towards lower grade and stage disease. It may not be surprising, therefore, that the PSA screened arm may have less aggressive disease. What we ultimately want to understand is whether unscreened men with a FH present with more aggressive disease. This question may have been better addressed by comparing those with a positive FH undergoing screening with those with a positive FH not undergoing screening. Previous studies conducted in this fashion suggested a difference in PCa mortality among men with a positive FH [5]. Unfortunately, these data were not available in the ERSPC. Future studies that continue to evaluate this question may elucidate whether FH predisposes to more aggressive disease.

Another factor that may have impeded the results of the present study is that men aged <55 years were not included in ERSPC. It is possible that FH predisposes to more aggressive cancers earlier in life, in men as young as 40 years. There is evidence that relative risk and risk for early-onset disease increases when a father or brother is diagnosed at a younger age, <60 years [6]. Future studies incorporating this younger cohort of men should therefore be conducted.

Until it has been clarified whether men with a positive FH of PCa are at risk of more aggressive disease, PSA screening strategies that begin at young ages should be used. In this fashion, it will be possible to selectively test populations of men at highest risk of developing PCa. Once these men have been screened, clinicians will be able to distinguish men with aggressive disease from those with more indolent disease. We believe that this shifts the focus to a different question: to treat or not to treat? Future research should continue to focus on methods of identifying those men who will go on to develop aggressive disease. Until then, men with low grade disease should continue to be followed by active surveillance [3].

Christina G. Selkirk* and Brian T. Helfand
*Center for Medical Genetics, Department of Medicine, NorthShore University Health System, and John and Carol Walter Center for Urological Health, Department of Surgery, NorthShor e University HealthSystem, Chicago, IL, USA

 

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