Heidi A. van Vugt

Prediction of Prostate Cancer Risk: The Role of Prostate Volume and Digital Rectal Examination in the ERSPC Risk Calculators

BACKGROUND The European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators (RCs) are validated tools for prostate cancer (PCa) risk assessment and include prostate volume (PV) data from transrectal ultrasound (TRUS). OBJECTIVE Develop and validate an RC based on digital rectal examination (DRE) that circumvents the need for TRUS but still includes information on PV. DESIGN, SETTING, AND PARTICIPANTS For development of the DRE-based RC, we studied the original ERSPC Rotterdam RC population including 3624 men (885 PCa cases) and 2896 men (547 PCa cases) detected at first and repeat screening 4 yr later, respectively. A validation cohort consisted of 322 men, screened in 2010-2011 as participants in ERSPC Rotterdam. MEASUREMENTS Data on TRUS-assessed PV in the development cohorts were re-coded into three categories (25, 40, and 60 cm3) to assess the loss of information by categorization of volume information. New RCs including PSA, DRE, and PV categories (DRE-based RC) were developed for men with and without a previous negative biopsy to predict overall and clinically significant PCa (high-grade [HG] PCa) defined as T stage>T2b and/or Gleason score≥7. Predictive accuracy was quantified by the area under the receiver operating curve. We compared performance with the Prostate Cancer Prevention Trial (PCPT) RC in the validation study. RESULTS AND LIMITATIONS Areas under the curve (AUC) of prostate-specific antigen (PSA) alone, PSA and DRE, the DRE-based RC, and the original ERSPC RC to predict PCa at initial biopsy were 0.69, 0.73, 0.77, and 0.79, respectively. The corresponding AUCs for predicting HG PCa were higher (0.74, 0.82, 0.85, and 0.86). Similar results were seen in men previously biopsied and in the validation cohort. The DRE-based RC outperformed the PCPT RC (AUC 0.69 vs 0.59; p=0.0001) and a model based on PSA and DRE only (AUC 0.69 vs 0.63; p=0.0075) in the relatively small validation cohort. Further validation is required. CONCLUSIONS An RC should contain volume estimates based either on TRUS or DRE. Replacing TRUS measurements by DRE estimates may enhance implementation in the daily practice of urologists and general practitioners.

Prediction of prostate cancer in unscreened men: External validation of a risk calculator

BACKGROUND Prediction models need external validation to assess their value beyond the setting where the model was derived from. OBJECTIVE To assess the external validity of the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator (www.prostatecancer-riskcalculator.com) for the probability of having a positive prostate biopsy (P(posb)). DESIGN, SETTING AND PARTICIPANTS The ERSPC risk calculator was based on data of the initial screening round of the ERSPC section Rotterdam and validated in 1825 and 531 men biopsied at the initial screening round in the Finnish and Swedish sections of the ERSPC respectively. P(posb) was calculated using serum prostate specific antigen (PSA), outcome of digital rectal examination (DRE), transrectal ultrasound and ultrasound assessed prostate volume. MEASUREMENTS The external validity was assessed for the presence of cancer at biopsy by calibration (agreement between observed and predicted outcomes), discrimination (separation of those with and without cancer), and decision curves (for clinical usefulness). RESULTS AND LIMITATIONS Prostate cancer was detected in 469 men (26%) of the Finnish cohort and in 124 men (23%) of the Swedish cohort. Systematic miscalibration was present in both cohorts (mean predicted probability 34% versus 26% observed, and 29% versus 23% observed, both p<0.001). The areas under the curves were 0.76 and 0.78, and substantially lower for the model with PSA only (0.64 and 0.68 respectively). The model proved clinically useful for any decision threshold compared with a model with PSA only, PSA and DRE, or biopsying all men. A limitation is that the model is based on sextant biopsies results. CONCLUSIONS The ERSPC risk calculator discriminated well between those with and without prostate cancer among initially screened men, but overestimated the risk of a positive biopsy. Further research is necessary to assess the performance and applicability of the ERSPC risk calculator when a clinical setting is considered rather than a screening setting.

Disease insight and treatment perception of men on active surveillance for early prostate cancer

Study Type – Survey (prospective cohort)
Level of Evidence 1b

Prospective validation of a risk calculator which calculates the probability of a positive prostate biopsy in a contemporary clinical cohort

BACKGROUND Prediction models need validation to assess their value outside the development setting. OBJECTIVE To assess the external validity of the European Randomised study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC) in a contemporary clinical cohort. METHODS The RC calculates the probability of a positive sextant prostate biopsy (P(posb)) using serum prostate-specific antigen (PSA), results of digital rectal examination, transrectal ultrasound (TRUS) and ultrasound assessed prostate volume. We prospectively validated the RC in 320 biopsied men (55-75 years), with no previous prostate biopsy, included in five Dutch hospitals in 2008-2011. If the P(posb) was ≥ 20% a biopsy was recommended. The performance of the RC was tested by comparing the observed outcomes to predicted probabilities, using the area under the curve (AUC) and decision curves analyses. RESULTS Compared to the screening cohort, men in the clinical cohort differed. They had higher PSA levels (median 6.8 versus 4.3 ng/ml, p<0.01), less TRUS-lesions (27% versus 34%, p = 0.01) and more prostate cancer (PCa) at biopsy (43% versus 25%, p<0.01). Mainly eight biopsy cores were taken. Despite the differences between these cohorts, the mean observed probability agreed with the mean predicted probability (43% versus 40%). The RC predicted P(posb) better than a model with PSA and digital rectal examination, AUC 0.77 (95% confidence interval (CI) 0.72-0.83) and 0.71 (95%CI 0.65-0.76, p<0.01), respectively. This was confirmed by the decision curves analysis. Under the 20% threshold, 17% (11/63) of the biopsied men were diagnosed with PCa. Two of 11 men had an important cancer (Gleason 3+4). CONCLUSIONS The ERSPC RC performs well in a Dutch clinical cohort in men with previous PSA tests and contemporary biopsy schemes, and outperforms a PSA and DRE-based approach in the decision to perform a biopsy.

Compliance with biopsy recommendations of a prostate cancer risk calculator

Study Type – Diagnostic (cohort)

Selecting men diagnosed with prostate cancer for active surveillance using a risk calculator: a prospective impact study

Study Type – Prognosis (cohort series)

Informed decision making on PSA testing for the detection of prostate cancer: an evaluation of a leaflet with risk indicator.

BACKGROUND Population-based screening for prostate cancer (PCa) remains controversial. To help men making informed decisions about prostate specific antigen (PSA) screening a risk indicator (www.uroweb.org) was developed. This risk indicator is embedded in a leaflet that informs men about the pros and cons of PCa screening and enables calculation of the individual risk of having a biopsy detectable PCa. AIM To assess the effect of providing a leaflet including individualized risk estimation on informed decision making of men, i.e. knowledge about PCa and PSA screening, attitude towards undergoing a PSA test and intention to have a PSA test. METHODS An intervention study among 2000 men, aged 55-65 years, randomly selected from the population registry of the city of Dordrecht, the Netherlands, in 2008. Men were sent a questionnaire on knowledge of PCa, attitude and intention to have a PSA test. Men without a history of (screening for) PCa were sent the leaflet and Questionnaire 2 within 2 weeks after returning Questionnaire 1. Validated health and anxiety measures were used. RESULTS One thousand and twenty seven of 2000 men completed Questionnaire 1 (51%), of whom 298 were excluded due to a history of (screening for) PCa. Of the 729 remaining men, 601 completed Questionnaire 2 as well. At the second assessment significantly more men met the requirements of informed decision making (15% versus 33%, p<0.001), more men had relevant knowledge (284/601, 50% versus 420/601, 77%, p<0.001) and the intention to have a PSA test had increased (p<0.001). CONCLUSIONS Providing information on PCa screening combined with individualized risk estimation enhanced informed decision making and may be used for shared decision making on PSA screening of physicians and patients.

Should prostate-specific antigen screening be offered to asymptomatic men?

The benefits of population-based prostate cancer screening are the detection of clinically important prostate cancers at an early, still curable, stage and the subsequent reduction of prostate cancer-specific mortality. However, a prostate-specific antigen (PSA)-based prostate cancer screening program is currently insufficient to warrant its introduction as a public health policy. The main reasons are insufficient knowledge regarding the optimal screening strategy and overdiagnosis and overtreatment of indolent prostate cancers that are unlikely to lead to complaints or death. In some countries, guidelines have been developed on screening for prostate cancer, but the diversity of recommendations illustrates the limited knowledge on the optimal strategy. Therefore, men should be well informed about the benefits and potential harms of PSA screening in order to enable them to make an informed decision. Although a mortality reduction can be achieved by early detection of prostate cancer, patients and physicians must be aware of the current side effects of screening. Algorithms that advise screening at a young age (<55 years), with screening intervals of less than 4 years and low PSA thresholds (<3 ng/ml) for prostate biopsy seem premature and are not supported by evidence.

Selecting men diagnosed with prostate cancer for active surveillance using a risk calculator

Study Type – Prognosis (cohort series)

Selecting men diagnosed with prostate cancer for active surveillance using a risk calculator: a prospective impact study: SELECTING MEN FOR ACTIVE SURVEILLANCE WITH RISK CALCULATOR

Study Type – Prognosis (cohort series)