Abstract 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.
Abstract Background Evidence from randomized trials on the effects of screening for prostate cancer (PCa) on disease-specific mortality accumulates slowly with increasing follow-up. Objective To ...assess data on PCa-specific mortality in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial. Design, setting, and participants A randomized controlled trial with randomization after signed, written informed consent (efficacy trial). In the period 1993–1999, a total of 42 376 men aged 54–74 yr were randomized to a screening arm (S-arm) ( n = 21 210 with screening every 4 yr, applying a total prostate-specific antigen PSA level cut-off ≥3.0 ng/ml as biopsy indication) or a control arm (C-arm) ( n = 21 166; no intervention). Outcome measurements and statistical analysis Number of PCas detected per arm depicted by predefined time periods and prognostic groups. PCa-specific mortality analyses using Poisson regression in age group 55–74 yr at randomization and separately in the predefined age group of 55–69 yr. Results and limitations After a median follow-up of 12.8 yr, 19 765 men (94.2%) were screened at least once and 2674 PCas were detected (of which 561 21.0% were interval PCas). In the C-arm, 1430 PCas were detected, resulting in an excess incidence of 59 PCas per 1000 men randomized (61 PCas per 1000 in age group 55–69 yr). Thirty-two percent of all men randomized have died. PCa-specific mortality relative-risk (RR) reductions of 20.0% overall (age: 55–74 yr; p = 0.042) and 31.6% (age: 55–69 yr; p = 0.004) were found. A 14.1% increase was found in men aged 70–74 yr (not statistically significant). Absolute PCa mortality was 1.8 per 1000 men randomized (2.6 per 1000 men randomized in age group 55–69 yr). The number needed to invite and number needed to manage were 565 and 33, respectively, for age group 55–74 yr, and 392 and 24, respectively, for age group 65–69 yr. Given the slow natural history of the disease, follow-up might be too short. Conclusions Systematic PSA-based screening reduced PCa-specific mortality by 32% in the age range of 55–69 yr. The roughly twofold higher incidence in the S-arm underlines the importance of tools to better identify those men who would benefit from screening.
Background
Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer ...diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGFβ1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer-specific survival.
Materials and methods
Retrospective survival analysis of forty-four prostate cancer patients, that underwent radical prostatectomy, was performed (1989–2001). Age, Gleason score and pre-treatment PSA levels were collected. IL-7, IL-7 receptor and TGFβ1 levels in prostate cancer tissue were determined by quantitative real-time RT-PCR and their additional prognostic value analyzed with regard to prostate cancer survival. Hazard ratios and their confidence intervals were estimated, and Akaike’s information criterion was calculated for model comparison.
Results
The predictive ability of a model for prostate cancer survival more than doubled when TGFβ1 and IL-7 were added to a model containing only the Gleason score and pre-treatment PSA (AIC: 18.1 and AIC: 6.5, respectively).
Conclusion
IL-7 and TGFβ1 are promising markers to indicate those at risk for poor prostate cancer survival. This additional information may be of interest with regard to the biological aggressiveness of the diagnosed prostate cancer, especially for those patients screened for prostate cancer and their considered therapy.
To compare tumour characteristics at the time of diagnosis of cancers detected in the screening and control arm at the Rotterdam section of the European Randomized study of Screening for Prostate ...Cancer.
Data were retrieved from the Rotterdam section of the ERSPC. Men were randomized to the screening arm (n=21,210) or the control arm (n=21,166). Men randomized to screening were offered PSA testing every 4 years. Through linkage with the cancer registry, men randomized to the control arm were detected. The biopsy Gleason score was determined in 1,591 and 373 patients in the screening and control arm, respectively. TURP, radical prostatectomy (RP) and cystoprostatectomy were evaluated for Gleason score, pathological (p)T stage and tumour volume.
More prostate cancers were detected in the screening arm (15.9 vs. 4.2 per 1000 man years, p<0.0001). Clinical stage distribution as well as biopsy and RP Gleason score distribution were significantly less favourable in the control arm. The incidence in man years of advanced disease (i.e. T4/N1/M1) was higher in the screening arm (6.0 per 100,000) as compared to the control arm (4.6 per 100,000). The 5-year PSA progression free survival after RP was 68% in the control arm and 89% in the screening arm (p<0.0001). The proportion of Incidental prostate cancers was 9.3% of all cancers detected in the control arm.
Although the number of men with advanced prostate cancer is slightly higher in the screening arm, the proportion of prostate cancers with favourable features is increased in the screening arm as compared to that in the control arm.
Background: Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer ...diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGF beta 1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer-specific survival. Materials and methods: Retrospective survival analysis of forty-four prostate cancer patients, that underwent radical prostatectomy, was performed (1989-2001). Age, Gleason score and pre-treatment PSA levels were collected. IL-7, IL-7 receptor and TGF beta 1 levels in prostate cancer tissue were determined by quantitative real-time RT-PCR and their additional prognostic value analyzed with regard to prostate cancer survival. Hazard ratios and their confidence intervals were estimated, and Akaike's information criterion was calculated for model comparison. Results: The predictive ability of a model for prostate cancer survival more than doubled when TGF beta 1 and IL-7 were added to a model containing only the Gleason score and pre-treatment PSA (AIC: 18.1 and AIC: 6.5, respectively). Conclusion: IL-7 and TGF beta 1 are promising markers to indicate those at risk for poor prostate cancer survival. This additional information may be of interest with regard to the biological aggressiveness of the diagnosed prostate cancer, especially for those patients screened for prostate cancer and their considered therapy.
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