Screening for early prostate cancer is frequently employed in the routine management of men with lower urinary tract symptoms (LUTS), but the evidence-base linking LUTS with prostate cancer is limited. We assessed the association of LUTS with a subsequent prostate cancer diagnosis in a prospective cohort study based on 21,159 Norwegian men who completed baseline questionnaires, including the International Prostate Symptom Score (IPSS) questionnaire, between 1995 and 2007 as part of the second NordTrøndelag Health Study (HUNT 2). Men were followed-up for prostate cancer incidence and mortality from the date of clinical examination to end 2005. During a mean of 9 years follow-up, 518 incident prostate cancers were diagnosed and 74 men died from prostate cancer. Men with severe LUTS Moderate to severe lower urinary tract symptoms (LUTS), including frequency, urgency, nocturia, incomplete emptying, hesitancy, weak stream and straining, are reported in up to 30-50% of men over 50 years old.1,2 Men with LUTS often worry that their symptoms indicate prostate cancer, 3,4 while a substantial proportion of clinicians perceive an established link between LUTS and prostate cancer 5 and recommend screening for early cancer using the prostate specific antigen (PSA) test in men with urinary symptoms.
5-7Whether screening for early prostate cancer does more good than harm is controversial 8 and the link between LUTS and prostate cancer is unclear.5 A systematic review of studies to 2000 revealed only 2 directly relevant papers 5 : in a large cohort from the pre-PSA era, recent onset of symptoms was associated with a 4-to 5-fold increased prostate cancer risk 9 ; in contrast, amongst 1,167 men who underwent PSA screening and had a biopsy for a raised PSA level, LUTS were associated with a 30% lower prostate cancer risk. 10 The latter finding (in men undergoing prostate biopsy, LUTS are associated with lower cancer risk) has been replicated in 2 studies, 11,12 but not in others. 13,14 In line with the pre-PSA cohort, 9 a recent case-control study from the UK, where PSA screening is not recommended, showed that individual LUTS were associated with 2-to 11-fold increased risks of a subsequent prostate cancer diagnosis.
15Rather than prostate cancer causing urinary symptoms per se, these studies suggest the possibility that the findings are due to biases that prompt the search for prostate cancer 9,15 or that affect the accuracy of biopsy. [10][11][12] For example, in the pre-PSA cohort 9 and UK case-control study, 15 it is unlikely that the identification of prostate cancer was independent of LUTS (verification bias). In men with LUTS, the existence of benign prostatic hyperplasia in large prostates may reduce the likelihood of detecting prostate cancer at biopsy, 13,16 generating an artifactual inverse association between LUTS and prostate cancer in analyses restricted to men undergoing biopsy.
10-12The majority of cancers develops in the peripheral zone of the prostate and would probably need to be advanced to provoke LUTS. The...