[Show abstract][Hide abstract] ABSTRACT: To describe mechanisms behind and extent of overdetection in prostate cancer screening as well as possible ways to avoid unnecessary overdiagnosis.
Overdetection and overtreatment is common in many areas of modern medicine. Current prostate-specific antigen (PSA) testing has resulted in a marked stage shift to early stages, which, together with improvements in treatment, has resulted in a substantial decrease in prostate cancer mortality. However, nonselective, widespread PSA-testing followed by liberal biopsy criteria has resulted in a high rate of overdiagnosis, which constitutes one major obstacle to introducing population-based screening.
Several steps are needed to decrease overdetection: do not screen elderly men unlikely to benefit, do not biopsy without a compelling reason, differentiate screening interval according to risk, work-up benign prostate disease by using reflex tests and/or complementary biomarkers, and focus on screening men at high risk for a life-threatening disease, for example evaluate men with above-median PSA levels in midlife. Recent results indicate that use of MRI to select men for biopsy and using only lesion-directed biopsies may be one way forward. However, more studies are needed before firm recommendations can be made. When the diagnosis is made, treat only those who need treatment. Tailor treatment to tumor biology and patient characteristics, and offer active surveillance to eligible men with low-risk tumors, especially small-volume disease, as the first management.
Current opinion in urology 03/2014; · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effect of prostate-specific antigen (PSA) screening on prostate cancer mortality remains debated, despite evidence from randomized trials. We investigated the association between prostate cancer incidence, reflecting uptake of PSA testing, and prostate cancer mortality.
The study population consisted of all men aged 50 to 74 years residing in eight counties in Sweden with an early increase in prostate cancer incidence and six counties with a late increase during two time periods. Incidence of metastatic prostate cancer was investigated in the period from 2000 to 2009, and prostate cancer-specific mortality and excess mortality were investigated in the period from 1990 to 1999 and the period from 2000 to 2009 by calculating rate ratios for high- vs low-incidence counties and rate ratios for the period from 2000 to 2009 vs the period from 1990 to 1999 within these two groups. All statistical tests were two-sided.
There were 4528134 person-years at risk, 1577 deaths from prostate cancer, and 1210 excess deaths in men with prostate cancer in high-incidence counties and 2471373 person-years at risk, 985 prostate cancer deaths, and 878 excess deaths in low-incidence counties in the period from 2000 to 2009. Rate ratios in counties with high vs low incidence adjusted for time period were 0.81 (95% confidence interval [CI] = 0.73 to 0.90) for prostate cancer- specific mortality and 0.74 (95% CI = 0.64 to 0.86) for excess mortality, and the rate ratio of metastatic prostate cancer was 0.85 (95% CI = 0.79 to 0.92).
The lower prostate cancer mortality in high-incidence counties reflecting a high PSA uptake suggests that more-intense as compared with less-intense opportunistic PSA screening reduces prostate cancer mortality.
[Show abstract][Hide abstract] ABSTRACT: Oncologic and functional outcomes after radical prostatectomy (RP) can vary between surgeons to a greater extent than is expected by chance. We sought to examine the effects of surgeon variation on functional and oncologic outcomes for patients undergoing RP for prostate cancer in a European center.
The study comprised 1,280 men who underwent open retropubic RP performed by one of nine surgeons at an academic institution in Sweden between 2001 and 2008. Potency and continence outcomes were measured preoperatively and 18 months postoperatively by patient-administered questionnaires. Biochemical recurrence (BCR) was defined as a prostate-specific antigen (PSA) value > 0.2 ng/mL with at least one confirmatory rise. Multivariable random effect models were used to evaluate heterogeneity between surgeons, adjusting for case mix (age, PSA, pathological stage, and grade), year of surgery, and surgical experience.
Of 679 men potent at baseline, 647 provided data at 18 months with 122 (19%) reporting potency. We found no evidence for heterogeneity of potency outcomes between surgeons (P = 1). The continence rate for patients at 18 months was 85%, with 836 of the 979 patients who provided data reporting continence. There was statistically significant heterogeneity between surgeons (P = 0.001). We did not find evidence of an association between surgeons' adjusted probabilities of functional recovery and 5-year probability of freedom from BCR.
Our data support previous studies regarding a large heterogeneity among surgeons in continence outcomes for patients undergoing RP. This indicates that some patients are receiving sub-optimal care. Quality assurance measures involving performance feedback, should be considered. When surgeons are aware of their outcomes, they can improve them to provide better care to patients.
[Show abstract][Hide abstract] ABSTRACT: The advantages and disadvantages of two different methods of analyzing the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial with respect to the effect of prostate-specific antigen (PSA) screening on prostate cancer (PCa) mortality (ie, disease-specific mortality analysis and excess mortality analysis) are discussed in depth. The traditional disease-specific mortality is the best end point, but it could be biased by misclassification of causes of death, and it does not take into account the possible effect of the screening process on other causes of death. Excess mortality analysis overcomes these problems, but the results could be biased if the expected mortality is not corrected for attendance status. Both methods, when applied to the ERSPC trials, demonstrate that no increase in non-PCa mortality occurred in the screening group and confirm that PSA screening decreases PCa mortality.
[Show abstract][Hide abstract] ABSTRACT: To determine the relative risks of prostate cancer incidence, metastasis, and mortality associated with screening by serum prostate specific antigen (PSA) levels at age 60.
Population based cohort study.
General male population of Sweden taking part in a screening trial in Gothenburg or participating in a cardiovascular study, the Malmö Preventive Project.
The screened group consisted of 1756 men aged 57.5-62.5 participating in the screening arm of the Gothenburg randomized prostate cancer screening trial since 1995. The unscreened group consisted of 1162 men, born in 1921, participating in the Malmö Preventive Project, with PSA levels measured retrospectively in stored blood samples from 1981.
PSA screening versus no screening.
Incidence rate ratios for the effect of screening on prostate cancer diagnosis, metastasis, and death by PSA levels at age 60.
The distribution of PSA levels was similar between the two cohorts. Differences in benefits by baseline PSA levels were large. Among men with baseline levels measured, 71.7% (1646/2295) had a PSA level <2 ng/mL. For men aged 60 with PSA level <2 ng/mL, there was an increase in incidence of 767 cases per 10 000 without a decrease in prostate cancer mortality. For men with PSA levels ≥2 ng/mL, the reduction in cancer mortality was large, with only 23 men needing to be screened and six diagnosed to avoid one prostate cancer death by 15 years.
The ratio of benefits to harms of PSA screening varies noticeably with blood PSA levels at age 60. For men with a PSA level <1 ng/mL at age 60, no further screening is recommended. Continuing to screen men with PSA levels >2 ng/mL at age 60 is beneficial, with the number needed to screen and treat being extremely favourable. Screening men with a PSA level of 1-2 ng/mL is an individual decision to be based on a discussion between patient and doctor.
[Show abstract][Hide abstract] ABSTRACT: Background
The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years.
ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736.
With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 [1·58–1·69] including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88).
In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening.
Each centre had its own funding responsibility.
[Show abstract][Hide abstract] ABSTRACT: Purpose
To investigate readmission frequencies during the 90 days following radical prostatectomy and to assess readmission risk associated with potentially related variables.
Materials and Methods
Using the population-based, nationwide database Prostate Cancer data Base Sweden (PCBaSe), we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy (RP) as their primary treatment, and we used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load, and patient characteristics.
During the 90 postoperative days, 2,317 (10%) of the 24,122 men identified were non-electively readmitted, specifically 10% after retropubic radical prostatectomy (RRP), 9% after robot-assisted RP (RALP) and 11% after laparoscopic RP (LRP). The range in the readmission frequency between hospitals was 0-35%. A higher risk of readmission was associated with early calendar period (2009-2011 vs. 2000-2002: odds ratio (OR), 0.71; 95% confidence interval (CI), 0.61-0.83), greater age (≥70 years vs. <60 years: OR, 1.17; 95% CI, 1.00-1.36), higher risk category (high vs. low-risk category: OR, 1.78; 95% CI, 1.57-2.03), high comorbidity (Charlson comorbidity index ≥3 vs. 0: OR, 1.77; 95% CI, 1.29-2.44), and low hospital surgical volume (≥150 vs. <30 RPs per year: OR, 0.70; 95% CI, 0.60-0.81).
Readmission rates after different RP methods were similar, ranging from 9% to 11%, with a wide variation between hospitals. Readmission rates can be used as an indicator of perioperative care quality, but potential confounders need to be adjusted to avoid bias.
The Journal of urology 01/2014; · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective. The aim of this study was to strengthen the validity of future findings in the Laparoscopic Prostatectomy Robot Open (LAPPRO) study by investigating the extent of interobserver variability between local pathologists and re-evaluating reference pathologists. Material and methods. LAPPRO is a Swedish prospective study comparing robot-assisted laparoscopic prostatectomy to open retropubic radical prostatectomy. Patients were recruited from 2008 to 2011. A random selection of 289 prostatectomy specimens was re-evaluated, in a blind fashion, by two reference pathologists from a University Hospital in Denmark and compared with original reports from local pathologists. Results. The exact concordance rate of Gleason score (GS) between local and reference pathologists was 56% (Spearman correlation coefficient 0.54). Exact concordance rates (κ value) for pathological tumour stage (pT), extraprostatic extension (EPE), surgical margin status (SMS) and seminal vesicle invasion (SVI) were 87% (0.63), 86% (0.59), 92% (0.76) and 98% (0.82), respectively. In subanalyses for surgical technique, exact concordance rates of GS, pT, EPE, SMS and SVI were 58%, 83%, 84%, 90% and 97%, respectively, for surgical technique 1 (ST1), compared to 55%, 88%, 87%, 93% and 98%, for surgical technique 2 (ST2). In ST1 specimens undergrading of GS by the local pathologists compared to central review was more common than overgrading (26% vs 16%). The inverse relationship was seen in ST2 specimens (14% vs 32%). Conclusion. Re-evaluation of randomly selected prostatectomy specimens in the LAPPRO cohort showed comparable results compared to previous studies of this kind. A systematic variation in the assessment of GS exists, attributable to individual differences in judgement between pathologists. Dichotomising GS (≤ 7 vs ≥ 8) overcomes the systematic variation.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: In a previous publication from the Göteborg randomised screening trial from 2010, biennial prostate-specific antigen (PSA) screening for men ≤69 yr of age was shown to lower prostate cancer (PCa) mortality by 44%. The evidence of the optimal age to stop screening, however, is limited. OBJECTIVE: To examine the risk of PCa after the discontinuation of screening. DESIGN, SETTING, AND PARTICIPANTS: In December 1994, 20 000 men in Göteborg, Sweden, between the ages of 50 and 65 yr were randomised to a screening arm (invited biennially to PSA testing) and a control arm (not invited). At the upper age limit (average: 69 yr), a total of 13 423 men (6449 and 6974 in the screening and control arms, respectively) were still alive without PCa. The incidence of PCa hereafter was established by matching with the Western Swedish Cancer Register. Participants were followed until a diagnosis of PCa, death, or final follow-up on June 30, 2012, or for a maximum of 12 yr after the last invitation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence rates and disease-free survival were calculated with life table models and Kaplan-Meier estimates. A competing risk model was also applied. RESULTS AND LIMITATIONS: Postscreening, 173 cases of PCa were diagnosed in the screening arm (median follow-up: 4.8 yr) and 371 in the control arm (median follow-up: 4.9 yr). Up to 9 yr postscreening, all risk groups were more commonly diagnosed in the control arm, but after 9 yr the rates in the screening arm caught up, other than those for the low-risk group. PCa mortality also caught up after 9 yr. CONCLUSIONS: Nine years after the termination of PSA testing, the incidence of potentially lethal cancers equals that of nonscreened men. Considering the high PCa mortality rate in men >80 yr of age, a general age of 70 yr to discontinue screening might be too low. Instead, a flexible age to discontinue based on individual risk stratification should be recommended.
[Show abstract][Hide abstract] ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Previous studies have shown that a statistical model based on a panel of kallikrein markers in blood (total, free and intact PSA and kallikrein-related peptidase 2) can predict prostate cancer on biopsy. The current study explores the relationship between the above-mentioned panel and prostate volume, and whether this panel could be an alternative for clinical measures such as DRE and TRUS in predicting prostate cancer on biopsy. OBJECTIVE: To explore whether a panel of kallikrein markers in blood: total, free and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2, could be used as a non-invasive alternative for predicting prostate cancer on biopsy in a screening setting. SUBJECTS AND METHODS: The study cohort comprised previously unscreened men who underwent sextant biopsy owing to elevated PSA (≥3 ng/mL) in two different centres of the European Randomized Study of Screening for Prostate Cancer, Rotterdam (n = 2914) and Göteborg (n = 740). A statistical model, based on kallikrein markers, was compared with one based on established clinical factors for the prediction of biopsy outcome. RESULTS: The clinical tests were found to be no better than blood markers, with an area under the curve in favour of the blood measurements of 0.766 vs. 0.763 in Rotterdam and 0.809 vs. 0.774 in Göteborg. Adding digital rectal examination (DRE) or DRE plus transrectal ultrasonography (TRUS) volume to the markers improved discrimination, although the increases were small. Results were similar for predicting high-grade cancer. There was a strong correlation between the blood measurements and TRUS-estimated prostate volume (Spearman's correlation 0.60 in Rotterdam and 0.57 in Göteborg). CONCLUSIONS: In previously unscreened men, each with indication for biopsy, a statistical model based on kallikrein levels was similar to a clinical model in predicting prostate cancer in a screening setting, outside the day-to-day clinical practice. Whether a clinical approach can be replaced by laboratory analyses or used in combination with decision models (nomograms) is a clinical judgment that may vary from clinician to clinician depending on how they weigh the different advantages and disadvantages (harms, costs, time, invasiveness) of both approaches.
[Show abstract][Hide abstract] ABSTRACT: Objective In addition to disease-specific mortality, a randomized controlled cancer screening trial may be evaluated in terms of excess mortality, in which case no patient-specific information on causes of death is needed. We studied the effect of not accounting for attendance on the calculated excess mortality in a prostate cancer screening trial.Methods The numerator of the excess mortality rate related to prostate cancer diagnoses in each study arm equals the excess number of deaths observed in the cancer patients. The estimation of the expected number of deaths in the absence of the prostate cancer diagnoses has to account for the self-selection of those participating in the trial, particularly if the proportion of non-participants is substantial.Setting The European prostate cancer screening trial (ERSPC).Results In the screening arm, non-attendees had roughly twice the mortality rate of attendees. Approximately twice as many cancers were detected in the screening arm compared with the control arm, primarily in attendees. Unless attendance is properly accounted for, the expected mortality of prostate cancer patients in the screening arm is overestimated by 0.9-3.6 deaths per 1000 person-years.Conclusions Attendees have a lower all-cause mortality rate (are healthier) and a higher probability of a prostate cancer diagnosis than non-attendees and the men randomized to the control arm. If attendance is not accounted for, the excess mortality and the between-arm excess mortality rate ratio are underestimated and screening is considered more effective than it actually is. These effects may be sizeable, notably if non-attendance is common. Correcting for attendance status is important in the calculation of the excess mortality rate in prostate cancer patients that can be used in conjunction with a disease-specific mortality analysis in a randomized controlled cancer screening trial.
Journal of Medical Screening 02/2013; · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17-19 November 2011, with the participation of a multidisciplinary panel of leading professionals including experts in methodological aspects. Before the conference, the expert panel prepared clinically relevant questions about prostate cancer in four areas for discussion as follows: diagnosis and staging, management of early localized disease, management of advanced localized disease and systemic disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective. The aim of this study was to identify preoperative patient and tumour-related factors associated with 12 months postoperative urinary incontinence. Material and methods. In total, 1529 men who had undergone radical prostatectomy for clinically localized prostate cancer between September 2008 and February 2010 at 15 Swedish hospitals completed a questionnaire before, 3 and 12 months after surgery. Urinary leakage, comorbidity and possible confounders were measured by self-administered validated questionnaires. Clinical data were collected preoperatively and postoperatively. The primary outcome, incontinence, was defined as the change of one pad or more per day. The ratio of proportions, estimated according to the log-binomial regression model, was analysed for 38 different factors and is presented as relative risks with 95% confidence intervals. Age-adjusted relative risk was calculated in the corresponding bivariate regression model. Results. Prospective data were available from 1360 men (response rate 89%). Results showed that age at surgery predicts long-term urinary incontinence exponentially. Patients reporting urinary leakage before prostate cancer diagnosis had an age-adjusted relative risk of 1.8 (95% confidence interval 1.3-2.4) for incontinence 12 months postoperatively. No statistically significant correlation was found between previous transurethral resection of the prostate, high body mass index or the other 34 evaluated factors and postoperative incontinence. Conclusions. Of 38 possible risk factors only age at surgery and preoperative urinary leakage were associated with 12 months postoperative incontinence in this study comprising 1360 men operated with radical prostatectomy. These findings may help the surgeon to have a targeted risk conversation with the patient before the treatment decision is made.
Scandinavian Journal of Urology and Nephrology 11/2012; · 1.01 Impact Factor