Claartje Gosselaar

Early Detection of Prostate Cancer in 2007: Part 1: PSA and PSA Kinetics

OBJECTIVE This is the first of two review papers attempting to clarify the best way to detect prostate cancer (PCa) in 2007. Screening for PCa has not yet been shown to lower PCa mortality. Still, opportunistic screening is wide spread in Europe and in most other parts of the world. METHODS Current literature and data from screening studies are reviewed and discussed. Prostate-specific antigen (PSA) has been and remains one of the corner stones of early detection of PCa. Traditionally used cut-off values cannot be applied in an uncritical fashion after it was shown that a significant amount of overdiagnosis and that large proportions of cancers and poorly differentiated cancers are present in the low PSA ranges. The paper addresses the continued relevance of PSA cut-off values. The diagnostic value of PSA velocity is reviewed in conjunction with PSA cut-off values and as a possible replacement of total PSA. A need for more selective screening in the low PSA ranges is pointed out. RESULTS AND CONCLUSIONS The data show that men presenting initially with PSA values below 1 do not have to be rescreened for a period of 8 yr. In the PSA range 1-2.9 ng/ml, new parameters are needed that improve specificity and are selective for screening for aggressive lesions. PSA velocity so far has not been shown to be useful in the early detection of PCa but may be useful in detecting aggressive PCa selectively. For the time being, it seems sensible to continue using PSA cut-off values such as 3.0 or 4.0 ng/ml provided overtreatment is decreased by using available nomograms.

Review – Prostate CancerEarly Detection of Prostate Cancer in 2007: Part 1: PSA and PSA Kinetics

OBJECTIVE This is the first of two review papers attempting to clarify the best way to detect prostate cancer (PCa) in 2007. Screening for PCa has not yet been shown to lower PCa mortality. Still, opportunistic screening is wide spread in Europe and in most other parts of the world. METHODS Current literature and data from screening studies are reviewed and discussed. Prostate-specific antigen (PSA) has been and remains one of the corner stones of early detection of PCa. Traditionally used cut-off values cannot be applied in an uncritical fashion after it was shown that a significant amount of overdiagnosis and that large proportions of cancers and poorly differentiated cancers are present in the low PSA ranges. The paper addresses the continued relevance of PSA cut-off values. The diagnostic value of PSA velocity is reviewed in conjunction with PSA cut-off values and as a possible replacement of total PSA. A need for more selective screening in the low PSA ranges is pointed out. RESULTS AND CONCLUSIONS The data show that men presenting initially with PSA values below 1 do not have to be rescreened for a period of 8 yr. In the PSA range 1-2.9 ng/ml, new parameters are needed that improve specificity and are selective for screening for aggressive lesions. PSA velocity so far has not been shown to be useful in the early detection of PCa but may be useful in detecting aggressive PCa selectively. For the time being, it seems sensible to continue using PSA cut-off values such as 3.0 or 4.0 ng/ml provided overtreatment is decreased by using available nomograms.

The Role of the Digital Rectal Examination in Subsequent Screening Visits in the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam

BACKGROUND The value of digital rectal examination (DRE) as a screening test for prostate cancer (PC) is controversial in the current prostate-specific antigen (PSA) era. OBJECTIVES To determine (1) the additional value of a suspicious DRE for the detection of PC in men with an elevated PSA level in subsequent screenings and (2) the tumour characteristics of PCs detected in men with a suspicious DRE. DESIGN, SETTING, PARTICIPANTS Within the screening study, from 1997-2006 men aged 55-75 years were invited for an every 4-yr PSA determination. A PSA level > or =3.0ng/ml prompted a DRE and a transrectal ultrasound (TRUS)-guided, lateralized sextant biopsy. Throughout the three screenings of the ERSPC, Rotterdam, 5040 biopsy sessions were evaluated. MEASUREMENTS We determined the positive predictive values (PPVs) of a suspicious DRE and normal DRE, which entailed, respectively, the proportion of PCs detected in men with a suspicious DRE or normal DRE divided by, respectively, all biopsied men with a suspicious DRE or normal DRE. RESULTS AND LIMITATIONS At initial screening, the PPV of a suspicious DRE, in conjunction with an elevated PSA level, to detect PC was 48.6% compared to 22.4% for men with a normal DRE. Both PPVs decreased in consecutive screens: respectively, 29.9% versus 17.1% (screen 2) and 21.2% versus 18.2% (screen 3). Respectively, 71.0% (p<0.001), 68.8% (p<0.001), and 85.7% (p=0.002) of all PCs with a Gleason score >7 were detected in men with a suspicious DRE at screens 1, 2, and 3. A limitation is that only biopsied men were evaluated. CONCLUSIONS At initial and subsequent screenings, the chance of having cancer at biopsy was higher in men with a suspicious DRE compared to men with a normal DRE (to a lesser extent in subsequent screenings), and the combination of a PSA level > or =3.0ng/ml with a suspicious DRE resulted in detecting significantly more PCs with Gleason score >7. DRE may be useful in more selective screening procedures to decrease unnecessary biopsies and overdiagnosis.

Prevalence and characteristics of screen-detected prostate carcinomas at low prostate-specific antigen levels: aggressive or insignificant?

Screening for prostate cancer at low prostate‐specific antigen (PSA) levels (≤4.0 ng/mL) risks detecting clinically insignificant cancers, which are of no threat to the man. In this review we evaluate the prevalence and tumour characteristics of prostate cancer detected at low PSA levels, comparing screening studies, cystoprostatectomy series and autopsy data. The favourable characteristics of tumours detectable at very low PSA levels seem to justify the conclusion that an unknown but sizeable proportion of the cancers found at biopsy are clinically insignificant.

The interobserver variability of digital rectal examination in a large randomized trial for the screening of prostate cancer.

To analyze to what extent the percentage of suspicious digital rectal examination (DRE) findings vary between examiners and to what extent the percentage of prostate cancers (PCs) detected in men with these suspicious findings varies between examiners.

The value of an additional hypoechoic lesion‐directed biopsy core for detecting prostate cancer

To determine the value of a hypoechoic lesion (HL)‐directed biopsy in addition to a systematic sextant biopsy for detecting prostate cancer.

Digital Rectal Examination and the Diagnosis of Prostate Cancer—a Study Based on 8 Years and Three Screenings within the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam

BACKGROUND Evidence indicates that an abnormal digital rectal examination (DRE) is a risk factor for high-grade prostate cancer (PC). OBJECTIVE To determine whether men with an initially suspicious DRE, a prostate-specific antigen (PSA) level > or = 3.0 ng/ml, and a benign prostate biopsy are at higher risk for significant PC at rescreening than men with an initially normal DRE, and whether an adaptation of the rescreening interval is warranted for this group. DESIGN, SETTING, AND PARTICIPANTS Within the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam, 2218 men underwent biopsy of the prostate (from 1993 to 2000) with a benign result at initial screening. The serum PSA was determined every 4 yr. A PSA level of > or = 3.0 ng/ml prompted a DRE and a lateralised sextant biopsy. MEASUREMENTS Number and characteristics of PCs found at repeat screenings and as interval cancers (ICs) were compared between men with or without a suspicious DRE result at initial screening. Multivariate logistic regression analyses were performed to evaluate if an initially suspicious DRE was a significant predictor for detecting cancer at consecutive screenings. RESULTS AND LIMITATIONS After 4 yr, the total number of PCs detected in men with and without an initially suspicious DRE was, respectively, 27 (6%) versus 103 (6%) (p=0.99). After 8 yr these numbers increased, respectively, to 45 (10%) versus 167 (10%) (p=0.88). The proportion of clinically significant PCs was 2% and 3%, respectively, for the group with initially normal and abnormal DRE after 8 yr. Having a suspicious DRE result at initial screening was not a significant predictor for detecting PC after 4 yr [odds ratio (OR)=1.15, p=0.59) or 8 yr (OR=1.41, p=0.43)]. A limitation of this study is the relatively short follow-up of 8 yr. CONCLUSIONS During a follow-up of 8 yr after initial cancer-negative biopsy, an initially suspicious DRE did not influence the chance for detection of cancer or significant cancer at later screens. An adaptation of the rescreening interval on the basis of the initial DRE-outcome is not warranted in future population-based screening for prostate cancer.

Metastatic disease of screen-detected prostate cancer: Characteristics at diagnosis

Screening for prostate cancer has not only led to a stage migration, but also to a higher incidence of the disease. A decrease in mortality has occurred in several countries during the same time period. Risk stratification of screen‐detected cancers at diagnosis has become more important for the anticipation and interpretation of changing incidence/mortality ratios.