Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high risk (>3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening.     

Disparities in prostate cancer screening,diagnoses, management,and outcomes between Indigenous and non-Indigenous men in a universal health care system

Background

Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought.

Methods

An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals.

Results

Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50–70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25–65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2–4.2; p < .01) than non-Indigenous men.

Conclusions

Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.     

Clinical Significance of Prostate Specific Antigen for Early Stage Prostate Cancer Detection

The characteristics of serum prostate specific antigen (PSA)in normal Japanese men were studied in 1480 subjects examinedby mass screening (MS) for prostate cancer (Pea) in Gunma Prefecturein 1992. The serum PSA concentration was correlated with patientage. The average serum PSA level increased by 0.04 ng/ml/year.The upper normal limits (95 percentiles)of age specific PSAfor normal men are 1.33 ng/ml for those aged 39–49 years,3.65 ng/ml for those aged 50–59 years, 4.06 ng/ml forthose aged 60–69 years, 5.09 ng/ml for those aged 70–79years and 5.66 ng/ml for those aged 80–89 years. Among227 normal men examined by our MS in 1991 and 1992, the PSAvelocity (PSAV) was calculated to be 0.05 ng/ml/year. Among10 Pea patients with normal PSA levels ( < 6 ng/ml) detectedpreviously by our MS, three had an abnormal PSAV. We demonstratedthe possibility that PSA density could distinguish between Peaand benign prostate hypertrophy. The significance of PSA asa Pea screening modality should be evaluated across multipleage ranges and in combination with previous PSA data and/orprostate volume estimated by sonography.     

Optimal prostate-specific antigen screening interval for prostate cancer

BackgroundTo identify the optimal interval for repeat prostate-specific antigen (PSA) testing to screen for prostate cancer in healthy adults.Patients and methodsA retrospective cohort study was conducted on 7332 healthy males without prostate cancer at baseline from 2005 to 2008. Participants underwent annual health checkups including PSA testing at the Center for Preventive Medicine in Japan. Participants with high PSA (≥4.0 ng/ml) underwent further examination for prostate cancer. A subgroup analysis was conducted age group (<50 years, ≥50 years).ResultsMean age was 50 years. Mean PSA at baseline was 1.2 ng/ml. In over 50-year group, for those with initial PSA of <1.0, 1.0–1.9, 2.0–2.9, and 3.0–3.9 ng/ml at baseline, the 3-year cumulative incidence of prostate cancer was 0%, 0.1%, 0.3%, and 5.7%, respectively. No prostate cancer was identified in those <50 years, regardless of PSA level.ConclusionsIf PSA screening is recommended, males >50 years with PSA of 3.0–3.9 ng/ml at baseline should undergo rescreening at 2 years. For men with PSA <3.0 ng/ml, PSA rescreening at intervals of ≥3 years is appropriate. PSA screening may not be indicated in males of <50 years of age.     

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

BackgroundPopulation-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.AimTo 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.MethodsAn 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.ResultsOne 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).ConclusionsProviding 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.     

Lead time associated with screening for prostate cancer

Screening serum levels of prostate-specific antigen (PSA) is now a major strategy for early detection of prostate cancer (PC). Quantification of the lead time thus obtained is important both for understanding the development of PC and for evaluating the advantages and disadvantages of widespread screening. In our study, 1,233 randomly selected men living in Stockholm in 1988 were invited to participate in an early detection (ED) program, in which suspicious findings provided by digital rectal examination (DRE), transrectal ultrasonography (TRUS) and/or a PSA value >/=10.0 ng/mL were followed up by biopsy. The cumulative incidence (Kaplan-Meier) of PC in the 946 participants (ED) during 12 years of follow-up was compared to that of an age-matched, randomly selected reference population (RP) of 657 men for whom PSA values (from frozen serum samples) could also be obtained. The PC incidence in men in the RP with PSA values >/=3.0 ng/mL reached the corresponding level for the ED group after 10.6 years (the "catch-up" point). After 12 years of follow-up, the estimated median lead time for men with PSA values in this interval was 4.5 years in the ED population, compared to 7.8 years in the RP. With 20 years of follow-up, the estimated median lead time of the RP was enhanced to 10.7 years. The lead time in connection with PC was influenced by the initial PSA level (although with large variations), length of follow-up and sensitivity of the ED procedure employed. The ED program described here was not associated with major overdetection.     

Cumulative probability of PSA increase above 4.0 NG/ML in population-based screening for prostate cancer

Routine screening for prostate cancer remains controversial. However, it is very important to show how the optimal rescreening interval should be set for men who want to be screened after informed consent. To solve this issue, the risk of prostate-specific antigen (PSA) increase above 4.0 ng/ml relative to baseline PSA levels and age was investigated. Between 1988 and 2000, 7,757 subjects screened twice or more and also with baseline PSA levels of 4.0 ng/ml or lower were enrolled in our study. All serum PSA levels were measured by E-test Tosoh II PA assay at one center. Interval PSA levels for men undergoing screening with a greater than 1 year interval were calculated on the assumption that PSA levels changed over time in a simple exponential fashion. Then, the cumulative rate of freedom from PSA increase above 4.0 ng/ml was estimated using the Kaplan-Meier technique stratified by baseline PSA ranges of 0.0 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 ng/ml and every 10 years of age ranges. Of the 7,757 subjects, 559 (7.2%) were expected to have had PSA levels increase above 4.0 ng/ml within 5 years after the baseline PSA measurements. The cumulative rate of freedom from the PSA increase above 4.0 ng/ml at 5 years was 98.7%, 92.9%, 70.3% and 38.5% in cases of baseline PSA levels of 1.0 ng/ml or lower, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively. The cumulative rates of freedom from the PSA increase were significantly decreased with the baseline PSA ranges being higher regardless of age range. Re-screening interval should be set stratified by baseline PSA levels, regardless of age and race. Rescreening interval should be set at 1, 1 to 2 and 3 to 5 years for men with baseline PSA ranges of 2.1 to 4.0 ng/ml, 1.1 to 2.0 ng/ml and 0.0 to 1.0 ng/ml, respectively, in individual-based screening. In mass screening system using PSA alone, rescreening interval should be set in the same manner as in individual-based screening, except for men with baseline PSA levels of 1.1 to 2.0 ng/ml, which should be set at 1 year to avoid developing incurable prostate cancer.     

Prostate cancer mortality in screen and clinically detected prostate cancer: Estimating the screening benefit

BackgroundTo 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.MethodsBetween 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.ResultsMedian 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.ConclusionsA 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.     

Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis

AimsThere is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure.Materials and methodsIndividual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42–54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan–Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases.ResultsSix hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9–7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5–31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1–311.6, P = 0.003).Conclusion4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.     

Salvage Radiotherapy for Recurrent Prostate Cancer: Can the Prognostic Grade Group System Inform Treatment Timing?

PurposeIn order to better time salvage radiotherapy (SRT) for post–radical prostatectomy biochemical failure, we examined the association between pre-SRT prostate-specific antigen (PSA) and PSA control as a function of the new prognostic grade group (PGG) system.Patients and MethodsUsing the Shared Equal Access Regional Cancer Hospital database, we identified men after radical prostatectomy with PSA > 0.2 ng/mL and without cancer involvement of lymph nodes who underwent SRT alone. SRT failure was defined as post-SRT PSA nadir + 0.2 ng/mL or receipt of post-SRT hormone therapy. Men were stratified by pre-SRT PSA (0.2-0.49, 0.5-0.99, and ≥ 1.0 ng/mL). Multivariable Cox models were used to test the association between pre-SRT PSA and SRT failure, stratified by PGG.ResultsA total of 358 men met the inclusion criteria and comprised our study cohort. Median post-SRT follow-up was 78 months. A total of 174 men (49%) had pre-SRT PSA 0.2-0.49 ng/mL, 97 (27%) PSA 0.5-0.99 ng/mL, and 87 (24%) PSA ≥ 1.0 ng/mL. On multivariable analysis among men with PGG 1-2, pre-SRT PSA 0.2-0.49 ng/mL had similar outcomes as PSA 0.5-0.99 ng/mL; those with PSA ≥ 1.0 ng/mL had higher recurrence risks (hazard ratio = 2.78, P < .001). Among PGG 3-5, PSA 0.5-0.99 ng/mL or ≥ 1.0 ng/mL had a higher recurrence risk (hazard ratio = 2.15, P = .021; and hazard ratio = 2.49, P = .010, respectively) versus PSA 0.2-0.49 ng/mL.ConclusionIn men with higher-grade prostate cancer (PGG 3-5), SRT should be provided earlier (PSA < 0.5 ng/mL), while among men with lower-grade disease (PGG 1-2), SRT results in equal PSA control up to PSA 1.0 ng/mL.     

Family history in the Finnish Prostate Cancer Screening Trial

Family history (FH) is one of the few known risk factors for prostate cancer (PC). There is also new evidence about mortality reduction in screening of PC with prostate‐specific antigen (PSA). Therefore, we conducted a prospective study in the Finnish Prostate Cancer Screening Trial to evaluate the impact of FH on outcomes of PC screening. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm and were invited for screening with PSA test (cut‐off 4 ng/ml) every 4 years. At the time of each invitation, FH of PC (FH) was assessed through a questionnaire. The analysis covered a follow‐up of 12 years from randomization for all men with data on FH. Of the 23,702 (74.3%) invited men attending screening, 22,756 (96.0%) provided information of their FH. Altogether 1,723 (7.3%) men reported at least one first‐degree relative diagnosed with PC and of them 235 (13.6%) were diagnosed with PC. Men with a first‐degree FH had increased risk for PC (risk ratio (RR) 1.31, p < 0.001) and the risk was especially elevated for interval cancer (RR 1.65, 95% CI 1.27–2.15). Risk for low‐grade (Gleason 2–6) tumors was increased (RR 1.46, 95% CI 1.15–1.69), but it was decreased for Gleason 8–10 tumors (RR 0.48, 95% CI 0.25–0.95). PSA test performance (sensitivity and specificity) was slightly inferior for FH positives. No difference in PC mortality was observed in terms of FH. Our findings provide no support for selective PSA screening targeting men with FH of PC.     

Maximum Tumor Diameter and the Risk of Prostate-Specific Antigen Recurrence After Radical Prostatectomy

Introduction/BackgroundThe aim of this study was to investigate whether the MTD could identify men at low risk of PSA recurrence after RP who might not benefit from ART despite other adverse features.Patients and MethodsThe study cohort consisted of 354 men with T1c to T2 prostate cancer diagnosed between September 2001 and December 2008 who underwent RP without adjuvant therapy. Multivariable Cox regression was used to assess the effect of MTD on the risk of PSA recurrence (> 0.1 ng/mL and verified), adjusting for known predictors.ResultsAfter a median follow-up of 4.0 years, 34 men (9.6%) experienced PSA failure. In multivariable analysis, increasing MTD was significantly associated with an increased PSA recurrence risk (hazard ratio, 2.74; 95% confidence interval, 1.23-6.10; P = .01) within the interaction model. Estimates of PSA recurrence-free survival stratified around the median MTD value (1.2 cm) were significantly different in men with a pre-RP PSA > 4 ng/mL (P < .001; 5-year estimate: 74.5% vs. 99.0%) but not in men with PSA ≤ 4 ng/mL (P = .59; 5-year estimate: 89.6% vs. 92.6%), consistent with the significant interaction (P = .004) between PSA and MTD. Moreover, in men with a pre-RP PSA > 4 ng/mL these estimates were significantly different if at least 1 adverse feature (pT3, R1, or Gleason score ≥ 8) was present at RP (P = .01; 5-year estimate: 46.6% vs. 100%) versus none (P = .09; 5-year estimate: 93.4% vs. 98.9%).ConclusionMen with a low MTD (≤ 1.2 cm) appear to be at low risk of PSA recurrence despite adverse features at RP and might not benefit from ART.     

Diagnostic Role of Serum Free-to-Total Prostate Specific Antigen (PSA) Ratio in Prostate Cancer with Serum Total Concentration of PSA below 4 ng/mL

Purpose: To examine the effectiveness of serum free-to-total prostate specific antigen ratio (%fPSA) forthe detection of prostate cancer (PCa) in men with different serum total PSA (tPSA) categories. Materials andMethods: From January 2010 to December 2013, a total of 225 patients with lower urinary tract symptoms(LUTS) underwent tPSA and %fPSA measurements. Histological examination with calculation of Gleasonscore and whole body bone scans were performed in identified cases of PCa. Results: PCa was diagnosed in 44(19.6%) patients and the remaining 181 patients had benign prostate disease. PCa was detected in 5 (23.8%),13 (8.7%) and 26 (47.3%) cases with tPSA level ranges ≤4 ng/ml, 4 to 10 ng/ml and >10 ng/ml, respectively. Theaverage Gleason score was 7.2±0.2. Some 6 (13.6%) out of 44 PCa patients had bone metastases. The sensitivitywas 80% and specificity was 81.3% at the cut-off %fPSA of 15% in PCa patients with a tPSA level below 4 ng/mL. A lower %fPSA was associated with PCa patients with Gleason score ≥7 than those with Gleason score≤6 (11.7±0.98 vs. 16.5±2.25%, P=0.029). No obvious relation of %fPSA to the incidence of bone metastasis wasapparent in this study. Conclusions: The clinical application of %fPSA could help to discriminate PCa frombenign prostate disease in men with a tPSA concentration below 4 ng/mL.     

Contemporary Pathological Stage Distribution After Radical Prostatectomy in North American High-Risk Prostate Cancer Patients

PurposeTo investigate pathological stage at radical prostatectomy (RP) using the “Partin tables” approach in NCCN high-risk (HR) prostate cancer (PCa) patients.Materials and MethodsWithin the SEER 2010 to 2016 database, we identified 7,718 NCCN HR PCa patients. Cross-tabulation was used to illustrate the distribution of organ confined disease (OC, pT2), extra-prostatic extension (EPE, pT3a), seminal vesicles invasion (SVI, pT3b), lymph node invasion (LNI, pT2N1), extra-prostatic and lymph node invasion (EPE + LNI, pT3aN1), and seminal vescicale and lymph node invasion (SVI + LNI, pT3bN1), according to preoperative criteria, which consisted in PSA, clinical T stage, biopsy Gleason Score (GS). Binomial 95%CI was constructed for the reported proportions.ResultsMedian (IQR) PSA levels was 9 (6-20) ng/ml. The majority of patient harbored cT1c (51%) followed by cT2 (35%) and cT3 (14%) stage. Most patients exhibited GS 4+4 (43%). Overall, 87 vs. 15 vs. 2% of patients harbored only 1 vs. 2 vs. all 3 HR criteria. At RP, OC, EPE, SVI, and LNI rates were respectively 36%, 27%, 17%, and 19%.Highest levels of OC were recorded for cT1c, PSA <10 ng/mL and biopsy GS4+4. Conversely, EPE, SVI and LNI were the highest in patients with cT3, PSA ≥20 ng/mL and GS 5+5. After stratification according to clinical stages, OC rates decreased with increasing PSA levels and GS. Conversely, EPE, SVI and LNI rates increased with increasing PSA and GS.ConclusionWe provide a lookup table to illustrate the relationship between clinical and pathological characteristics in NCCN HR PCa patients.     

Effective PSA contamination in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer

The extent of effective prostate-specific antigen (PSA) contamination in the Rotterdam section of the ongoing European Randomized Study of Screening for Prostate Cancer (ERSPC) trial was evaluated and defined as when opportunistic PSA testing of >/= 3.0 ng/ml was followed by biopsy, similar to the regular procedure within the trial. Records of participants aged 55-74 years at entry were linked to the regional database of the general practitioner (GP) laboratory to obtain PSA tests requested by GPs in the period 1 July 1997 to 31 May 2000 (2.9 years), and to the national pathology database to quantify the number of biopsies. All men randomized were included, only those with prostate cancer screen-detected or clinically diagnosed before July 1997 were omitted from the analyses. 2,895 out of the 14,349 men (20.2%) in the control arm and 1,981 out of the 14,052 men (14.1%) in the screening arm were PSA-tested, at an average annual rate of 73 and 52 per 1,000 person-years, respectively. These rates were higher than those recorded at the national and regional levels, 33 and 38 per 1,000 person-years, respectively. Opportunistic PSA testing in the control arm reached a peak within the first months of randomization, after which it decreased to around 70 per 1,000 person-years. An opposite pattern was observed in the screening arm, where participants already had received the scheduled screening within the trial. The proportion of men in the control arm with PSA >/= 3.0 ng/ml followed by biopsy and prostate cancer was 7-8% and 3%, respectively (3% and 0.4-0.6% in the screening arm), over the whole study period. Over a 4-year rescreening interval, the average PSA and effective contamination amount were approximately 28% and 10%, respectively. PSA testing in the control arm in the Rotterdam ERSPC section is high, but was not followed by a substantial increase in prostate biopsies. Although the reasons for ordering PSA test or indicating biopsy are unknown, effective PSA contamination in the Rotterdam ERSPC section is low and not likely to jeopardize the power of the trial.     

On the use of prostate-specific antigen for screening of prostate cancer in European Randomised Study for Screening of Prostate Cancer

Prostate-specific antigen (PSA) has been the main drive for early detection of prostate cancer (PCa), including in population-based screening as in the European Randomised Study for Screening of Prostate Cancer (ERSPC). The specificity of PSA to indicate men with biopsy detectable prostate cancer can be improved by adding information obtained by new biomarkers, such as PSA isoforms. This improvement is needed to increase the efficacy of the screening procedure for the population-based as well as the individual screening. Various PSA isoforms, kallikreins and molecular markers have been validated in various cohorts from ERSPC of men with and without PCa in order to design the optimal diagnostic procedure for screening asymptomatic men. So far, most promising results have been obtained from the analysis of free PSA, proPSA, nicked PSA and hK2. The use of free PSA in addition to total PSA reduces the number of negative sextant biopsies at a PSA cut-off level of 3 ng/ml at initial screening with 30%, at the cost of losing 10% of detectable cancers that are predominantly well differentiated on histology. Further addition of PSA isoforms and hK2 only improve ROC curves in selected samples by a maximum of 5%. Molecular markers like PCA3 and TMPRSS2 in urine do not appear to be useful but they have been assessed insufficiently so far. The level of PSA at initial screening is highly predictive for the chance of being diagnosed with PCa later on in life. The changes in PSA over time after initial screening (like PSA-velocity and PSA-doubling time) are statistically different between men with detectable cancers versus those without (PSA-doubling time 5.1 versus 6.1 years), but this does not contribute significantly to population-based screening overall. Changes in specificity need to be related to a cost efficacy evaluation in the final analysis of ERSPC.     

A National Survey of Radiation Oncologists and Urologists on Perceived Attitudes and Recommendations of Active Surveillance for Low-Risk Prostate Cancer

BackgroundClinical factors and barriers affecting adoption of active surveillance (AS) for low-risk prostate cancer (PCa) remain poorly understood. We performed a national survey of radiation oncologists (RO) and urologists (URO) about the perceptions and recommendations of AS for low-risk PCa.Materials and MethodsIn 2017, we surveyed 915 RO and 940 URO about AS for low-risk PCa in the United States. Survey items queried respondents about their attitudes toward AS and recommendations of AS for low-risk PCa. Pearson chi-square and multivariable logistic regression identified clinical and physician factors related toward AS for low-risk PCa.ResultsOverall, the response rate was 37.3% (n = 691) and was similar for RO and URO (35.7% vs. 38.7%; P = .18). RO were less likely to consider AS effective for low-risk PCa (86.5% vs. 92.0%; P = .04) and more likely to rate higher patient anxiety on AS (49.5% vs. 29.5%; P < .001) than URO. Recommendations of AS varied modestly on the basis of age, prostate-specific antigen (PSA), and number of cores positive for Gleason 3 + 3 PCa. For a 55-year-old man with PSA 8 with 6 cores of Gleason 6 PCa, both RO and URO infrequently recommended AS (4.4% vs. 5.2%; adjusted odds ratio = 0.6; P = .28). For a 75-year-old patient with PSA 4 with 2 cores of Gleason 6 PCa, URO and RO most often recommended AS (89.6% vs. 83.4%; adjusted odds ratio = 0.5; P = .07).ConclusionRO and URO consider AS to be effective in the clinical management of low-risk PCa, but this varies by clinical and physician factors.     

Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy

AimsTo report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution.Materials and methodsIn 2003–2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan–Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant.ResultsOf 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3–7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival.ConclusionIn low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.     

Pathologic Outcomes of Gleason 6 Favorable Intermediate-Risk Prostate Cancer Treated With Radical Prostatectomy: Implications for Active Surveillance

Background

The safety of active surveillance (AS) for Gleason 6 favorable intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy.

Active Surveillance Versus Radical Prostatectomy in Favorable-risk Localized Prostate Cancer

BackgroundActive surveillance (AS) and radical prostatectomy (RP) are both accepted treatments for men with favorable-risk localized prostate cancer (PCa) (ie, clinical tumor category 1-2b, Gleason Grade Group 1-2, and prostate-specific antigen < 20 ng/mL). However, head-to-head studies comparing oncologic outcomes and survival between these 2 treatment strategies are warranted. The objective of this study was to compare the use of prostate cancer treatments and PCa death in men managed on AS and men who underwent immediate RP.Patients and MethodsThis was an observational study including 647 men on AS and 647 men treated with RP propensity score matched. We examined the 10-year cumulative incidence of salvage radiotherapy, hormonal therapy, castration-resistant PCa, and PCa death.ResultsThe 10-year curative treatment-free survival for men on AS was 61% (95% confidence interval [CI], 57%-65%). No differences in use of salvage radiotherapy (AS, 2.7%; 95% CI, 1.4%-4.1% vs. RP 5.4%; 95% CI, 3.4%-7.3%), hormonal therapy (AS, 6.9%; 95% CI, 4.4%-9.4% vs. RP, 4.1%; 95% CI, 2.5%-5.6%), developing castration-resistant PCa (AS, 1.7%; 95% CI, 0.5%-2.9% vs. RP, 2.0%; 95% CI, 0.7%-3.4%), or cumulative PCa mortality (AS, 0.4%; 95% CI, 0%-1.0% vs. RP, 0.5%; 95% CI, 0%-1.5%) were observed between the treatment strategies. The main limitation was the non-random allocation to treatment strategy.ConclusionIn this observational study on men with favorable-risk localized PCa, we found similar PCa mortality at 10 years between men on AS and men who underwent immediate RP. Moreover, there were no differences in the use of PCa therapies between the groups. Our study supports active surveillance as a treatment strategy for men with favorable-risk localized PCa.