Search

Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age., Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2-4 yr)., Design, Setting, and Participants: We evaluated 25589 men aged 55-59 yr, 16898 men aged 60-64 yr, and 12936 men aged 65-69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2-4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU)., Outcome Measurements and Statistical Analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60-61 yr., Results and Limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2-1.5% for men with PSA <1.0 ng/ml to 13.3-13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60-61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60-61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68-70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76-78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice., Conclusions: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55-69 yr is a strong indicator to delay or stop further screening., Patient Summary: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: European Randomized Study of Screening for Prostate Cancer (ERSPC) mortality results were reported for 7 European countries (excluding France) and showed a significant reduction in Prostate cancer (PCa) mortality. As those results have not been part of the global ERSPC results, it is of interest to report PCa mortality at a median follow-up of 9 years for French section of ERSPC., Material and Methods: Two administrative departments were involved in the study. Only men after randomization in the screening group were invited by mail to be screened by PSA testing with two rounds at 4-6 year intervals. Biopsy was recommended if PSA>=3.0 ng/mL. No information other that the French Association of Urology recommandations on the use of PSA was offered to the control group (own decision of physicians and patients). Follow up was based on cancer registry database. Contamination defined as the receipt of PSA testing in control arm was measured. Poisson regression models were used to estimate the Rate Ratio (RR) of PCa mortality and incidence in the screening vs. control arm., Results: Starting from 2003, 80,696 men aged 55-69 years were included. The percentage of men in the screening arm with at least one PSA test (compliance) was 31%. Compared to the control arm, PCa incidence increased by 10% in the screening arm (RR=1.10; 95% CI=[1.04-1.16], P=0.001), but PCa mortality did not differ (0.222 and 0.215 deaths/1000 person-years; RR=1.03[0.75-1.42], P=0.9)., Discussion: Limitations include low participation rate. PSA testing in the control arm was observed in 32% of men (contamination)., Conclusions: Contamination in control group led to no effect of PSA-based screening on prostate cancer mortality at 9 years follow-up., Level of Evidence: 3., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality., Design, Setting, and Participants: Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis., Outcome Measurements and Statistical Analysis: Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis., Results and Limitations: In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03-2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16-1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89-1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52-0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller., Conclusions: The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr., Patient Summary: The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT)., Methods: Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses., Results: Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030)., Conclusions: In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

The analytical and clinical validation of new biomarkers for the early detection of prostate is necessary. (-2)proPSA, total PSA and free PSA values are used to calculate a standardized PHI index linked to a higher probability of a positive biopsy in patients with PSA levels between 3-4 and 10 ng/L, the gray zone for prostate cancer diagnosis. The purpose of this study is to validate the analytical performance of the (-2)proPSA and to determine the predictive value of PHI for the early detection of prostate cancer. Analytical performances are correct. It is not necessary to dilute samples before analysis. The stability of (-2)proPSA is good until at least 3 hours at room temperature before centrifugation. The study of the PSAT, PSAL, (-2)proPSA and PHI values in a population of patients consulting for an early prostate cancer diagnosis shows that the index PHI is the most powerful predictive marker of cancer with an area under ROC curve of 0.70, whereas it is only 0.56 for total PSA.

Background: Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up., Methods: The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer., Results: After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality., Conclusions: Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).

Objective: •To determine if the prostate-specific antigen (PSA) nadir after high-intensity focused ultrasound (HIFU) can be used as a predictor of the biochemical disease-free survival rate (DFSR)., Patients and Methods: •Patient data were derived from the multicentre-based @-Registry, the largest registry to report outcomes in patients with localized prostate cancer after Ablatherm® HIFU. •PSA level was measured at 3-month intervals. Patients were stratified into four PSA nadir groups: group 1, ≤0.2 ng/mL; group 2, 0.21-0.5 ng/mL; group 3, 0.51-1 ng/mL; and group 4, >1 ng/mL. •Biochemical treatment failure was defined according to the Stuttgart definition (PSA nadir + 1.2 ng/mL) and the Phoenix definition (PSA nadir + 2 ng/mL). •Biopsy was performed at 3-6 months post-HIFU or if a PSA level was recorded that was considered clinically relevant., Results: •The present study included 804 patients. Biochemical treatment success rates at 5 years according to the Stuttgart definition for the four PSA nadir sub-groups were as follows: 84, 64, 40 and 30% for groups 1-4, respectively. •The equivalent 5-year biochemical success rates using the Phoenix definition were 94, 74, 66 and 47%, respectively. •Significantly more patients had a negative biopsy in the lowest PSA nadir group than in the other sub-groups (91.6 vs 73.1%; P < 0.001). •The present study is limited by its retrospective nature and variations in clinical practice across participating centres., Conclusion: •This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objectives: To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high-intensity focused ultrasound (HIFU) for prostate cancer, to identify the most accurate predictor of clinical failure after HIFU., Patients and Methods: Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France; and Regensburg, Germany) were prospectively maintained within a central database and retrospectively reviewed for this study. Clinical failure was defined as a positive prostate biopsy after treatment, radiographic evidence of lymphatic or bony metastatic disease, or salvage treatment for prostate cancer (surgery, radiation, hormonal therapy or second HIFU). The serum prostate-specific antigen (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic success or failure. PSA threshold values, 'PSA nadir plus', PSA velocity, PSA doubling time and the American Society or Therapeutic Radiotherapy and Oncology and Phoenix definition of biochemical failure were all considered. The sensitivity, specificity, positive predictive value and negative predictive value of each biochemical definition for predicting clinical failure were determined., Results: The data from 285 patients (stage

Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm., Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination., Design, Setting, and Participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent)., Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam., Measurements: Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose., Results and Limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres., Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.

Introduction: Mass screening modalities remained controversial and made necessary large studies. The European Randomized study of Screening for Prostate cancer (ERSPC) was initiated in 1994. Eight countries including France are participating., Methods: ERSPC is a multicentric randomised study and started with the aim to determine whether a 20% reduction in prostate cancer mortality can be achieved with PSA-based screening. Men aged 50-74 and living in the Tarn or Hérault were included. After randomization and exclusion of men who died or had a prostate cancer were invited to participate by giving their consent and had a PSA test. In case of PSA greater than or equal to 3 ng/ml, biopsy was recommended. Included men in both screening and control group were followed through cancer registries. Objective was to present first round results of French participation to ERSPC, to determine factors of participation and to compare detected cancers cases between both groups., Results: Population of men included was 84,781 and were randomized in screening (n=42,590) or control (n=42,191) group. Participation rate was 36.9% in Tarn and 24.3% in Hérault. PSA was greater than or equal to 3 ng/ml in 15,4% of cases (n=1812) and 45.9% of men (n=832) who were biopsied. Age, previous PSA performed within two years prior to invitation, health insurance and department of residence were significantly associated to participation rate. Cumulated incidence with a four years follow-up was 2.48% (n=1053) in screening and 1.99% (n=840) in control group, with a relative risk (RR) of 1.242. Corresponding RR for Tarn and Hérault were 1.37 and 1.20 respectively. Clinical parameters and treatments modalities were similar between both screening and control groups (radical prostatectomy 68% and radiation therapy 20%)., Conclusion: Participation rate at first round was modest. Profile of men who participated compared to men who did not were different. The control group was probably contaminated by PSA testing outside study protocol. Consequences at ERSPC level of this low participation rate on final analysis remain to be determined.

Background: The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer., Methods: We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006., Results: In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90)., Conclusions: PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.), (2009 Massachusetts Medical Society)

A first serum total PSA assay is recommended during the first three months after treatment. When PSA is detectable, PSA assay should be repeated three months later to confirm this elevation and to estimate the PSA doubling time (PSADT). In the absence of residual cancer, PSA becomes undetectable by the first month after total prostatectomy: less than 0.1 ng/ml (or less than 0.07 ng/ml) for the ultrasensitive assay method and less than 0.2 ng/ml for the other methods. In the presence of residual cancer, PSA either does not become undetectable or increases after an initial undetectable period. A consensus has been reached to define recurrence as PSA greater than 0.2 ng/ml confirmed on two successive assays. After external beam radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 ng/ml (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 ng or more above the PSA nadir, whether or not it is associated with endocrine therapy. After endocrine therapy, the PSA nadir is correlated with recurrence-free survival. PSA is decreased for a mean of 18 to 24 months followed by a rise in PSA, corresponding to hormone-independence. The time to recurrence or the time to reach the nadir and the PSA doubling time after local therapy with surgery or radiotherapy have a diagnostic value in terms of the site of recurrence, local or metastatic and a prognostic value for survival and response to complementary radiotherapy or endocrine therapy. A PSADT less than eight to 12 months is correlated with a high risk of metastatic recurrence and 10-year mortality. The histological and biochemical characteristics in favour of local recurrence are Gleason score less or equal to seven (3+4), elevation of PSA after a period greater than 12 months and PSADT greater than 10 months. In other cases, recurrence is predominantly metastatic. The risk of demonstrating metastasis in the case of biochemical recurrence after total prostatectomy and before endocrine therapy depends on the PSA level and the PSADT. No consensus has been reached concerning the indication for complementary investigations by bone scan and abdominopelvic CT in patients with biochemical recurrence after treatment of localized cancer without endocrine therapy. However, when PSADT greater than six months, the risk of metastasis is less than 3% even for PSA greater than 30 ng/ml. When PSADT less than six months and PSA greater than 10 ng/ml, the risk of metastasis is close to 50%.

Objective: The measurement of PSA serum levels is central to all early detection programs for prostate cancer. Although individual PSA values were known to fluctuate in the short and long term, the influence of insolation and seasons on PSA had not been addressed to date. To assert the relationship between total and free PSA and meteorological data in 8644 participants (55-70 years) in the French arm of the ERSPC study., Methods: Blood sample was taken at the local laboratory after informed consent and frozen sera were sent for central testing of total and free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat with Hybritech reagents. Monthly meteorological data -- insolation, daily temperatures and rain precipitations -- were obtained from the local branches of the National Meteorology Agency., Results: Total PSA -- but not free PSA -- was correlated with insolation, that is the monthly accrual in hours of sunshine during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI: 0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and percent-free PSA (free PSA divided by the total PSA). Interdependence between total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such relationship was even more evident in summer when the tested participants more often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the year, resulting in 23% more chances of being referred for biopsies (Odds ratio 1.23, 95%CI: 1.10-1.40)., Conclusions: Total PSA was shown to be strongly associated with insolation and seasons while the percent-free PSA was not influenced., (European Association of Urology)

Prostate Specific Antigen (PSA) is currently the best marker for prostate cancer, although it is not very specific for this disease. The use of the PSA kinetic, in addition to its absolute value, is theoretically very attractive in a large number of clinical situations. Based on a review of the literature, the authors report the various methods used to study this kinetic, with particular emphasis on the most reliable method: the PSA doubling time. After describing the definitions and the methods used to calculate this parameter, the authors discuss the various clinical situations in which it could be useful: surveillance of prostatic tumours after the initial diagnosis in high-risk patients or patients refusing treatment, prognostic factor before curative treatment, evaluation of the efficacy of curative treatment, prognostic factor of tumour aggressiveness at the time of biochemical recurrence after curative treatment or during endocrine therapy.

The literature concerning the efficacy and safety of transrectal high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer still comprises a relatively small number of articles. The main studies have been published by four teams using an apparatus available in Europe for several years. The recently presented results of the European Multicentre Study and the study by Gelet and associates based on 242 patients with a follow-up of more than 1 year show that HIFU is a valid alternative for the management of welldifferentiated and moderately differentiated localized prostate cancer with an initial PSA 10 years. In two studies, the combination of transurethral resection of the prostate and HIFU limited the risk of postoperative urinary retention without inducing a higher complication rate. In a series of patients presenting recurrence after external-beam radiotherapy, HIFU was found to be a useful therapy, with >80% negative biopsies. The best indications for HIFU are men over the age of 65, those who are not candidates for radical prostatectomy, obese patients, or patients with comorbidities likely to make surgery more difficult. The learning curve for this technique is relatively short, between 10 and 15 patients, for urologists experienced in transrectal ultrasonography. One of the advantages of HIFU is that it can be repeated in the case of recurrence or to re-treat a prostatic site, it involves no radiation, and patients do not suffer from long-term irritative urinary symptoms.