Objective
To systematically review and meta‐analyse evidence regarding the additional value of magnetic resonance imaging (MRI) and MRI‐targeted biopsies to confirmatory systematic biopsies in ...identifying high‐grade prostate cancer in men with low‐risk disease on transrectal ultrasonography (TRUS) biopsy, as active surveillance (AS) of prostate cancer is recommended for men with Gleason 3 + 3 on standard TRUS‐guided biopsy. Confirmatory assessment can include repeat standard TRUS‐guided biopsy, and/or MRI with targeted biopsy when indicated.
Methods
A systematic review of the Embase, Medline, Web‐of‐science, Google scholar, and Cochrane library was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)‐2 criteria. Studies reporting men with Gleason 3 + 3 prostate cancer who had chosen AS based on transrectal systematic biopsy findings and had undergone MRI with systematic ± targeted biopsy at confirmatory assessment were included. The primary outcome was detection of any Gleason pattern ≥4.
Results
Included reports (six) of men on AS (n = 1 159) showed cancer upgrading (Gleason ≥3 + 4) in 27% (95% confidence interval CI 22–34%) using a combined approach of MRI‐targeted biopsies and confirmatory systematic biopsies. MRI‐targeted biopsies alone would have missed cancer upgrading in 10% (95% CI 8–14%) and standard biopsies alone would have missed cancer upgrading in 7% (95% CI 5–10%). No pathway was more favourable than the other (relative risk RR 0.92, 95% CI 0.79–1.06). In all, 35% (95% CI 27–43%) of men with a positive MRI were upgraded, compared to 12% (95% CI 8–18%) of men with a negative MRI being upgraded (RR 2.77, 95% CI 1.76–4.38).
Conclusions
A pre‐biopsy MRI should be performed before confirmatory systematic TRUS‐guided biopsies in men on AS, together with MRI‐targeted biopsies when indicated. A combined approach maximises cancer detection, although other factors within multivariate risk prediction can be used to aid the decision to biopsy in these men.
Repeated, prostate-specific antigen–based screening with a 4-yr interval in men aged 55–69 yr reduces prostate cancer–specific mortality and metastatic prostate cancer after a median follow-up of 21 ...yr. Additionally, coinciding overdiagnosis is lower than previously suggested.
Considering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial.
To provide an update on the effect of prostate-specific antigen (PSA)-based screening on PCa-specific mortality (PCSM), metastatic disease, and overdiagnosis in the Dutch arm of the ERSPC.
Between 1993 and 2000, a total of 42376 men, aged 55–74 yr, were randomised to a screening or a control arm. The main analysis was performed with men aged 55–69 yr (n = 34831). Men in the screening arm were offered PSA-based screening with an interval of 4 yr.
Intention-to-screen analyses with Poisson regression were used to calculate rate ratios (RRs) of PCSM and metastatic PCa.
After a median follow-up of 21 yr, the RR of PCSM was 0.73 (95% confidence interval CI: 0.61–0.88) favouring screening. The numbers of men needed to invite (NNI) and needed to diagnose (NND) to prevent one PCa death were 246 and 14, respectively. For metastatic PCa, the RR was 0.67 (95% CI: 0.58–0.78) favouring screening. The NNI and NND to prevent one metastasis were 121 and 7, respectively. No statistical difference in PCSM (RR of 1.18 95% CI: 0.87–1.62) was observed in men aged ≥70 yr at the time of randomisation. In the screening arm, higher rates of PCSM and metastatic disease were observed in men who were screened only once and in a selected group of men above the screening age cut-off of 74 yr.
The current analysis illustrates that with a follow-up of 21 yr, both absolute metastasis and mortality reduction continue to increase, resulting in a more favourable harm-benefit ratio than demonstrated previously. These data do not support starting screening at the age of 70–74 yr and show that repeated screening is essential.
Prostate-specific antigen–based prostate cancer screening reduces metastasis and mortality. Longer follow-up shows fewer invitations and diagnoses needed to prevent one death, a positive note towards the issue of overdiagnosis.
Background and purpose
Individualized risk-adapted algorithms in prostate cancer (PCa) diagnosis using predictive prebiopsy variables in addition to prostate-specific antigen value may result in a ...considerable reduction of unnecessary systematic biopsies. Multi-parametric magnetic resonance imaging (mpMRI) has emerged as a secondary prediction tool that can further improve the detection of clinically significant prostate cancer (csPCa). This review explores the performance of new MRI risk models for indicating a biopsy for prostate cancer diagnosis.
Results and considerations
The area under the receiver-operating characteristic curve for detecting csPCa varies between 0.64 and 0.91 in biopsy-naïve men, and between 0.78 and 0.93 in men with a previous negative biopsy. The utility of multivariate risk prediction tools including MRI suspicion scores as an extra input parameter has the potential to avoid a notable number of biopsies and detection of clinically insignificant PCa at a low price of missing some csPCa. The trade-off depends on the risk threshold that is chosen. In biopsy-naïve men a net benefit was obtained at a risk threshold of above 10% for csPCa in most MRI risk prediction models. All constructed MRI risk models used (referral) patient cohorts with high prevalence of csPCa. Using more representative cohorts from daily clinical screening, net benefit may attenuate at lower risk thresholds. Strengths and limitations of these models are discussed.
Future directions
To assess their wider applicability, in-depth analysis of mpMRI predictive qualities should be further investigated, in combination with required external validation of these models in a multicenter setting with large prospective datasets.
Abstract Background Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing ...interest as an alternative to radical treatment of low-risk PCa. Objective To update our experience in the largest worldwide prospective AS cohort. Design, setting, and participants Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤6. PSA was measured every 3–6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. Outcome measurements and statistical analysis Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy–free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. Results and limitations In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. Conclusions Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. Trial registration The current program is registered at the Dutch Trial Register with ID NTR1718 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718 ).
The optimal timing for discontinuing screening of prostate cancer (PCa) in elderly men is currently not known and remains debated.
To assess prostate cancer-specific mortality (PCSM) in elderly men ...who previously underwent prostate-specific antigen (PSA)-based screening and to identify those who may benefit from continued screening.
A total of 7052 men, who participated in the screening arm of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer and were aged 70-74 yr at their last screening visit after undergoing a maximum of three screening rounds without being diagnosed with PCa, were included.
The cumulative incidence of PCSM by the age of 85 yr was assessed. Additionally, a competing risk regression was performed to assess the potential predictors of PCSM.
The median follow-up was 16 yr. The cumulative incidence of PCSM by the age of 85 yr was 0.54% (95% confidence interval CI: 0.40-0.70) in all men, 0.11% (95% CI: 0.05-0.27) in men with PSA <2 ng/ml, 0.85% (95% CI: 0.47-1.5) in men with PSA 2-3 ng/ml, and 6.8% (95% CI: 3.1-15) in men with PSA ≥6.5 ng/ml and no previous benign biopsy. PSA (subdistribution hazard ratio sHR: 2.0; 95% CI: 1.7-2.3), previous benign prostate biopsy (sHR: 0.41; 95% CI: 0.23-0.72), and hypertension (sHR: 0.48; 95% CI: 0.25-0.91) were significantly associated with PCSM.
Men aged 70-74 yr who have previously undergone PSA-based screening without receiving a PCa diagnosis have a very low risk of dying from PCa by the age of 85 yr. These data suggest that screening may be discontinued in men with PSA <3.0 ng/ml or previous benign prostate biopsies. Those with higher PSA levels and no prior biopsies may consider continued screening if life expectancy exceeds 10 yr.
This study shows that men who participated in a prostate cancer screening trial have a very low risk of dying from prostate cancer if they have not been diagnosed with prostate cancer by the age of 74 yr.
Objective To compare the survival outcomes of patients treated with surgery or radiotherapy for prostate cancer. Design Observational study. Setting Sweden, 1996-2010. Participants 34 515 men ...primarily treated for prostate cancer with surgery (n=21 533) or radiotherapy (n=12 982). Patients were categorised by risk group (low, intermediate, high, and metastatic), age, and Charlson comorbidity score. Main outcome measures Cumulative incidence of mortality from prostate cancer and other causes. Competing risks regression hazard ratios for radiotherapy versus surgery were computed without adjustment and after propensity score and traditional (multivariable) adjustments, as well as after propensity score matching. Several sensitivity analyses were performed. Results Prostate cancer mortality became a larger proportion of overall mortality as risk group increased for both the surgery and the radiotherapy cohorts. Among patients with non-metastatic prostate cancer the adjusted subdistribution hazard ratio for prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to 2.08, for radiotherapy v prostatectomy), whereas there was no discernible difference in treatment effect among men with metastatic disease. Subgroup analyses indicated more clear benefits of surgery among younger and fitter men with intermediate and high risk disease. Sensitivity analyses confirmed the main findings. Conclusions This large observational study with follow-up to 15 years suggests that for most men with non-metastatic prostate cancer, surgery leads to better survival than does radiotherapy. Younger men and those with less comorbidity who have intermediate or high risk localised prostate cancer might have a greater benefit from surgery.
After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for ...prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain.
On the basis of ERSPC follow-up data, we used Microsimulation Screening Analysis (MISCAN) to predict the number of prostate cancers, treatments, deaths, and quality-adjusted life-years (QALYs) gained after the introduction of PSA screening. Various screening strategies, efficacies, and quality-of-life assumptions were modeled.
Per 1000 men of all ages who were followed for their entire life span, we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and a total of 73 life-years gained (average, 8.4 years per prostate-cancer death avoided). The number of QALYs that were gained was 56 (range, -21 to 97), a reduction of 23% from unadjusted life-years gained. To prevent one prostate-cancer death, 98 men would need to be screened and 5 cancers would need to be detected. Screening of all men between the ages of 55 and 74 would result in more life-years gained (82) but the same number of QALYs (56).
The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects. Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made. (Funded by the Netherlands Organization for Health Research and Development and others.).
The burden of prostate cancer is increasing. Therefore, we need to implement a contemporary, organized, risk-stratified program for early detection to reduce both the harm from the disease and ...potential overdiagnosis and overtreatment, while avoiding underdiagnosis to considerably improve the harm-to-benefit ratio.
Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent ...prognostic value for disease outcome, but are not included in the GG limiting their clinical use.
To perform a proof-of-principle study incorporating CR/IDC in the current GG.
All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent.
Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient.
Outcome measurements and statistical analysis disease-specific survival (DSS), metastasis-free survival (MFS), and biochemical recurrence–free survival (BCRFS) after 15.1 yr (interquartile range 10.9–19.7 yr) follow-up were compared using Harrell’s C-statistic.
The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74–0.83 vs 0.76; 0.71–0.82) and MFS (0.79; 0.74–0.84 vs 0.77; 0.72–0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study.
The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca.
Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that a simple grade modification better predicts Pca outcome and might improve treatment choices.
Pathological grading is an important parameter for decision making in prostate cancer patients. We show that a simple modification of the current International Society of Urologic Pathology/World Health Organization grade groups incorporating cribriform architecture results in a significantly better discriminative value for disease-specific and metastasis-free survival.
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