Objective: To develop and externally validate a predictive model for detection of significant prostate cancer. Patients and Methods: Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mp MRI ) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mp MRI followed by biopsy for abnormal prostate‐specific antigen ( PSA ) level or digital rectal examination ( DRE ). A model was developed with age, PSA level, DRE , prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System ( PIRADS ) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. Results: In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve ( AUC ) of 0.80, the advanced model (incorporating mp MRI ) had a significantly higher AUC of 0.88 ( P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer. Conclusions: Individualised risk assessment of significant prostate cancer using a predictive model that incorporates mp MRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over‐detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed.

To estimate the benefits of prostate-specific antigen (PSA) screening on prostate cancer (Pca) metastasis and Pca-specific mortality, we compared two populations with a well-defined difference in intensity of screening. Between 1997 and 1999, a total of 11,970 men, aged 55-74 years, were included in the intervention arm of the European Randomised Study of Screening for Prostate Cancer (ERSPC) section Rotterdam. Control population consisted of 133,287 men, aged 55-74 years, between 1998 and 1999 in Northern Ireland (NI). Men were followed for Pca incidence, Pca metastasis and cause of death until 31st December 2006. Median age in both groups was 63 years at study entry (p=0.184). In Rotterdam 94.2% of men and in NI 6% of men underwent PSA testing. In Rotterdam, 1153 men (9.6%) were diagnosed with Pca with median baseline PSA of 5.1 ng/ml. In NI, 3962 men (3.0%, p<0.001) were diagnosed with Pca with median baseline PSA of 18.0 ng/ml (p<0.001). The relative risk of Pca metastasis during observation in the intervention population compared to control population was 0.47 (95% confidence interval (CI), 0.35-0.63; p<0.001). The relative risk of Pca-specific mortality was also lower in the intervention population compared to the control population after a median follow-up of 8.5 years: 0.63 (95% CI, 0.45-0.88; p=0.008); absolute mortality reduction was 1.8 deaths per 1000 men. A relative reduction in Pca metastasis of 53% and Pca mortality of 37% was observed in the intervention population after 8.5 years of observation. The impact of overdiagnosis, quality of life benefits and cost-effectiveness need to be assessed before population-based PSA screening can be recommended.

BACKGROUND: The benefits of prostate cancer screening on an individual level remain unevaluated.METHODS: Between 1993 and 1999, a total of 43,987 men, aged 55‐74 years, were included in the intervention arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) section in the Netherlands, Sweden, and Finland. A total of 42,503 men, aged 55‐74 years, were included in a clinical population in Northern Ireland. Serum prostate‐specific antigen (PSA) <20.0 ng/mL was measured in all men at study entry. All men were followed for prostate cancer incidence and causes of death until December 31, 2006.RESULTS: The adjusted absolute difference in prostate cancer specific mortality between the intervention population and the clinical population increased with increasing PSA level at study entry, ie, 0.05 per 10,000 person‐years for men who had a serum PSA level of 0.0‐1.9 ng/mL and 8.8 per 10,000 person‐years for men who had a serum PSA level of 10‐19.9 ng/mL. To evaluate the risks of early detection, the number needed to investigate (NNI) and number needed to treat (NNT) to save 1 death from prostate cancer were calculated. Both NNI and NNT were higher for those who had lower PSA levels at study entry. The NNI was 24,642 men for patients who had a serum PSA level of 0.0‐1.9 ng/mL and was 133 men for patients who had a serum PSA level of 10‐19.9 ng/mL; the NNT was 724 men for patients who had a serum PSA level of 0.0‐1.9 ng/mL and was 60 men for patients with a serum PSA level of 10‐19.9 ng/mL.CONCLUSIONS: For men with a low serum PSA level, the benefits of aggressive investigation and treatment may be limited because they are associated with a large increase in cumulative incidence and potential overtreatment. Cancer 2010. © 2010 American Cancer Society.