The potential harms in screening
Explicit in the concerns regarding screening are the concerns related to biopsy and to overdiagnosis and overtreatment. About 15% of men in screening programs have false positive tests and undergo unnecessary biopsy, which has a 0.5%-1.0% serious complication rate. Moreover, many more men will be diagnosed with PCa (at least one in six) than will die of the disease (approximately one in 36), as death from PCa has been shown to be an infrequent occurrence in men with low risk, screen-detected disease.19, 20
It has been estimated that 25%-84% of screen detected PCa is overdiagnosed,14 with over 1.3 million such cancers diagnosed from 1986-2005.39 The detection of these tumors in USA frequently results in treatment: 91% of men in PLCO5 and 92.5% of men in CaPSURE40 were treated. Radical treatment is unlikely to yield a survival benefit in those with indolent disease41 or in those men older than 65 years,42 but can result in a significant decrease in quality of life as a result of potentially persistent urinary, sexual and bowel dysfunction.43
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The PIVOT trial of radical prostatectomy versus observation for men with screen detected cancer showed no improvement in survival.44 Fortunately, the overtreatment of patients with low-risk disease appears to be improving with time.40
The false positives associated with PCa screening have also been found to have a detrimental effect on mental health. Further, a population-based analysis revealed that a diagnosis of PCa was associated with a significant increase in cardiovascular events (RR 1.3, 95% CI [1.3-1.3]) and suicide (RR 2.6, 95% CI [2.1-3.0]) within the first year following diagnosis, with an even more pronounced effect noted in the first week after diagnosis.45
Economic concerns are also an important consideration with PCa screening. Using mathematical models, researchers concluded that the introduction of screening had resulted in an increase of costs for PCa by 100%, 39% of which was related to overdiagnosis. Screening costs were only a small part of the expenses related to PCa diagnosis, evaluation and treatment.46
Future directions
Moving forward with PSA screening at this point mandates careful selection of those men most likely to derive benefit. This population includes patients with a long life expectancy due to young age and minimal or no comorbidity13 given the indolent nature of most screen- detected PCa.15 Other populations that are likely to benefit from screening include patients at risk for aggressive disease, who are more likely to experience PCa mortality.
However, in the absence of specific markers for such disease, the identification of such patients remains challenging. Clinical variables may be evaluated in a variety of nomograms, models and on-line tools but their applicability to a specific patient is unclear.
Progress is being made with molecular tests47 on biopsy specimens that should assist with better risk prognostication and thus selection of more appropriate risk-based therapies for patients, such as active surveillance. It is hoped that selective screening, selective biopsy, and selective therapy will further decrease the NNT and morbidity associated with screening.
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