A clinical diagnosis of benign prostatic hyperplasia (BPH) appeared to be associated with an increased risk of prostate cancer, in a large cohort study. However, the authors caution that this does not mean that the association is causal.

This study attempted to examine the association between BPH and both the incidence of, and mortality from, prostate cancer. The entire male population of Denmark (3,009,258 men) were studied between 1980 and 2006. A total of 53,315 men were diagnosed with prostate cancer and 25,459 died from the disease.

A diagnosis of BPH was ascertained from hospitalisation (187,591), surgery (77,698), use of alpha-blockers (143,365) or 5-alpha reductase inhibitors (47,465).

Multivariate analysis was used to eliminate potential confounders and hazard ratios (HR) calculated for the risk of prostate cancer for each of these cohorts of men with BPH.

For all men hospitalised with BPH the HR was 2.2 (95% CI: 2.13-2.31), compared with general population controls, suggesting double the risk of a diagnosis of prostate cancer in these men. The HR was 3.26 (95% CI: 3.03-3.50) in men operated on for BPH.

The HRs for mortality ranged from 2.00 (95% CI: 1.91-2.08), for hospitalisation to 7.85 (95% CI: 7.40-8.32) for those who had received BPH-related surgery.

The authors conclude that a clinical diagnosis of BPH was associated with a two to three times increased risk of prostate cancer diagnosis and a two- to eight-fold increased risk of prostate cancer mortality over 27 years of follow-up.

There is conflicting evidence within the literature regarding the link between BPH and prostate cancer. There is increasing interest in the concept that both BPH and prostate cancer are linked with diabetes, hypertension, obesity and hyperlipidaemia and that the metabolic syndrome may be the common link between BPH and prostate cancer pathogenesis. Still, several large studies have failed to demonstrate a convincing link between these two conditions.

This study, while impressive in size and duration, can be criticised on a number of counts. First, with regards to prostate cancer incidence it is not clear if the authors were able to exclude convincingly so-called ‘ascertainment bias’, the concept that men with BPH would be more thoroughly investigated/screened for prostate cancer, thus increasing incidence rates.

Second, the study defined a prostate cancer death as a diagnosis of prostate cancer as the first, second or third listed cause of death on the death certificate. Therefore, a patient with BPH who had incidental prostate cancer discovered on PSA screening but died from an MI would be listed as a prostate cancer death, but a man without BPH with undiagnosed coincidental prostate cancer who also died from an MI would be classified as a non-prostate cancer death.

Many patients present to their GP with lower urinary tract symptoms as a result of benign disease because of their belief, encouraged by the lay media, that these symptoms are due to prostate cancer. Most GPs will have been asked by patients with BPH if they have, or are at risk of, developing prostate cancer. The orthodox answer to this is that there is no convincing evidence of a link between these two common conditions, but it is a hugely complex link to study and there is therefore no firm evidence that there is not a link.

While of great interest, this paper cannot therefore be said to demonstrate convincingly a link between BPH and prostate cancer. It does illustrate, however, the difficulty of designing a study sufficiently robust to determine categorically the presence or absence of such a link.

Dr Jonathan Rees

• Orsted D, Bojesen SE, Nielsen, SF, Nordestgaard BG. Association of clinical benign prostate hyperplasia with prostate cancer incidence and mortality revisited: A nationwide cohort study of 3 009 258 men. Eur Urol 2011;60:691-698