Prostate CancerA Risk-Based Strategy Improves Prostate-Specific Antigen–Driven Detection of Prostate Cancer
Introduction
Despite recent results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) that show relative mortality reduction up to 30% in favor of screening [1], [2], controversy still exists due to the absence of a risk–benefit analysis providing convincing evidence regarding its net effectiveness.
Prostate cancer (PC) screening using a serum prostate-specific antigen (PSA)–based threshold as a the sole indication for prostate biopsy lacks specificity, resulting in large numbers of unnecessary biopsies and, at the same time, in missing cancer diagnoses in men with PSA levels below the chosen PSA cut-off value.
Data coming from the Prostate Cancer Prevention Trial (PCPT) showed that the quantitative relation of PC prevalence and PSA is continuous [3]. This has opened the discussion of whether the PSA threshold indicating a prostate biopsy should be lowered to values of approximately 2.0 ng/ml or 2.5 ng/ml [4]. Lowering the PSA threshold would result in the detection of more PC but would also increase the number of unnecessary biopsies dramatically [5], [6], [7].
In order to reduce the number of unnecessary biopsies, many probability-based algorithms have been developed that use, besides the PSA level, additional relevant prebiopsy information such as age, results of digital rectal examination (DRE) and transrectal ultrasound (TRUS), and prostate volume [8], [9], [10], [11], [12], [13].
Another concern with respect to screening for PC are characteristics of the cancers that are detected through active screening. A considerable percentage of the screening-detected PCs are indolent and most probably do not need to be detected at all or can still be detected later in a curable stage [14], [15], [16], [17].
In the recently developed Riskindicator [18], [19], both issues—the reduction of biopsies and the identification of potentially indolent PC—are combined. In the current study, we assessed the reduction in number of potentially unnecessary biopsies using risk profile-based cut-off values as indicators for biopsy in men with a serum PSA ≥3.0 ng/ml and, at the same time, assessed the number of indolent PCs, important PCs, and related progression rates and PC deaths diagnosed or missed at an initial and repeat screening visit (4-yr interval).
Section snippets
Initial screening
During the period from May 1997 to December 1999, 10 191 men were screened using a serum PSA level of ≥3.0 ng/ml as the only indication for biopsy (Beckman Hybritech assay; Beckman Coulter, Inc., Fullerton, CA, USA). This cohort represents the second segment of the total cohort randomized to the screen arm of the Dutch part of the ERSPC (n = 19 970). The biopsy procedure consisted of a lateralized sextant biopsy and an additional seventh biopsy in case of a hypoechoic lesion.
Repeat screening
The second study
Cancer detection at initial screening
At initial screening, 2147 men (21.0%) had a PSA ≥3.0 ng/ml, 1850 were actually biopsied (90%), and 541 PCs were detected (Table 2). The positive predictive value (PPV; number of cancers found per number of biopsies done) was 29% (541 of 1850). The cancer detection rate (CDR; number of cancers found among the total number of men eligible) in this study setting was 5% (541 of 10 191). After a mean follow-up of 11 yr, 139 PC cases (26%) showed progression and 18 men died of their disease (1.7%) (
Discussion
We found that a PSA cut-off of 3.0 ng/ml as an indication for a prostate biopsy-based screening algorithm resulted in a predictive value for a positive biopsy of 29% at initial screening and 19% at repeat screening 4 yr later. This implies that respectively 71% and 81% of the biopsies may have been unnecessary if the cut-off value of ≥3.0 ng/ml is considered valid. Additional information available at the time of biopsy could be used to provide individualized predictions of the biopsy outcome.
Conclusions
A screening algorithm that uses, in addition to a PSA level of 3.0 ng/ml, other available prebiopsy information (ultrasound volume, outcomes of DRE and TRUS) and that also considers previous screening visits can result in a considerable reduction of unnecessary biopsies. Perhaps even more important, this strategy results in missing very few PC cases for which diagnosis at a subsequent screening visit might be too late for treatment with curative intent.
The proposed strategy, therefore, might
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