Prostate Cancer Mortality Among Elderly Men After Discontinuing Organised Screening:Long-term Results from the European Randomized Study of Screening for Prostate Cancer Rotterdam

Background: The optimal timing for discontinuing screening of prostate cancer (PCa) in elderly men is currently not known and remains debated. Objective: 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. Design, setting, and participants: 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. Outcome measurements and statistical analysis: 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. Results and limitations: 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 &lt;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. Conclusions: 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 &lt;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. Patient summary: 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.</p

A Detailed Evaluation of the Effect of Prostate-specific Antigen–based Screening on Morbidity and Mortality of Prostate Cancer:21-year Follow-up Results of the Rotterdam Section of the European Randomised Study of Screening for Prostate Cancer

Background: Considering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial. Objective: 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. Design, setting, and participants: Between 1993 and 2000, a total of 42 376 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 = 34 831). Men in the screening arm were offered PSA-based screening with an interval of 4 yr. Outcome measurements and statistical analysis: Intention-to-screen analyses with Poisson regression were used to calculate rate ratios (RRs) of PCSM and metastatic PCa. Results and limitations: 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. Conclusions: 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. Patient summary: 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.</p

Prostate Cancer Risk Calculator seems to prevent referrals to urologist

De NHG-Standaard Mictieklachten bij mannen adviseert om patiënten met een prostaatspecifiek antigeen (PSA)-waarde van ≥ 3 ng/mL voor nadere diagnostiek van prostaatkanker te verwijzen naar de uroloog. Risico-inschatting met PSA-waarde, rectaal toucher en prostaatecho ingevuld in het predictiemodel de Prostaatwijzer kan meer dan de helft van de prostaatbiopten voorkomen. Implementatie van deze Prostaatwijzer in een eerstelijns diagnostisch centrum resulteerde dan ook in een potentiële reductie van 68% in het aantal verwijzingen ten koste van slechts 1 (0,52%) gemiste klinisch significante prostaatkankerdiagnose. Het gebruik van de Prostaatwijzer in een eerstelijnssetting is daarom een potentieel veilige en patiëntvriendelijke strategie om zorgkosten, wachttijden en werkdruk te reduceren

PSA-tests bij mannen ouder dan 74 jaar: zwart-wit of toch een grijs gebied?

Men >70–74 years of age are excluded from PSA-based screening for prostate cancer because of overdiagnosis. In this study we will determine if we should apply PSA-based screening in elderly in terms of life expectancy and quality of life. Men aged between 70–74 years randomly assigned in the screening group of the Dutch ERSPC and not diagnosed with prostate cancer at time of screening were included. Incidence and mortality were described. In the end 3,040 men were included. During a follow up of 24 years, 202 (7%) were diagnosed with prostate cancer of which 52 (26%) developed metastasis and 26% died of prostate cancer. PSA at time of screening predicted prostate cancer specific mortality (PCSM). Concluded was that men > 74 years of age should not be refrained from screening given the risk of metastasis and the mortality rate. Health assessment and counseling together with PSA testing and further risk stratification are the key to a valid screening strategy

Interaction of MRI and active surveillance in prostate cancer: Time to re-evaluate the active surveillance inclusion criteria

Currently available data from long-running single- and multi-center active surveillance (AS) studies show that AS has excellent cancer-specific survival rates. For AS to be effective the ‘right’ patients should be selected for which up until 5-to-10 years ago systematic prostate biopsies were used. Because the systematic prostate strategy relies on sampling efficiency for the detection of prostate cancer (PCa), it is subject to sampling error. Due to this sampling error, many of the Gleason 3+3 PCas that were included on AS in the early days and were classified as low-risk, may in fact have had a higher Gleason score. Subsequently, AS-criteria were more strict to overcome or limit the number of men missing the potential window of curability in case their tumor would be reclassified. Five to ten years ago the prostate biopsy landscape changed drastically by the addition of magnetic resonance imaging (MRI) into the diagnostic PCa-care pathway, which has by now trickled down into the EAU guidelines. At the moment, the EAU guidelines recommend performing a (multi-parametric) MRI before prostate biopsy and combine systematic and targeted prostate biopsy when the MRI is positive (i.e. PIRADS ≥3). So because of the introduction of the MRI into the diagnostic PCa-care pathway, literature is showing that more Gleason 3+4 PCas are being diagnosed. But can it not be that the inclusion of MRI into the diagnostic PCa-care pathway causes risk inflation, resulting in men earlier eligible for AS, now being labelled ineligible for AS? Would it not be possible to include these current Gleason 3+4 PCas on AS? The authors hypothesize that the improved accuracy that comes with the introduction of MRI into the diagnostic PCa-care pathway permits to widen both the AS-inclusion and follow-up criteria. Maintaining our inclusion criteria for AS from the systematic biopsy era will unnecessarily and undesirably expose patients to the increased risk of overtreatment. The evidence behind the addition of MRI-targeted biopsies to systematic biopsies calls upon the re-evaluation of the AS inclusion criteria and research from one-size-fits-all protocols used so far, into the direction of more dynamic and individual risk-based AS-approaches

The transition from transrectal to transperineal prostate biopsy without antibiotic prophylaxis: Cancer detection rates and complication rates

Background: Currently, transperineal prostate biopsy (TPB) is preferred over transrectal biopsy (TRB) because of less infectious complications and improved clinically significant prostate cancer (csPCa) detection. However, literature on omitting antibiotic prophylaxis (AP) is limited. Furthermore, previous studies did not include invasive cribriform growth/intraductal carcinoma (CR/IDC) in the definition of csPCa. Therefore, we compared the infectious complication rates between TPB without AP and TRB with AP, and we compared the csPCa detection rates between TPB and TRB including CR/IDC in the definition of csPCa. Methods: We included 729 men who were referred to Erasmus MC Cancer Institute between 2013-2019 for MRI/TRUS fusion-guided prostate biopsy. Up to 2019, TRB was performed with AP, thereafter TPB was performed without AP. Data on complications were collected prospectively. We compared csPCa detection rates between the biopsy routes using multivariable logistic regressions for men without previous PCa diagnosis and mixed logistic regression for men on active surveillance. To compare the csPCa detection rates in anterior and apical lesions, and the complications rates between the biopsy routes, we used the chi-square test. Results: Overall, we found no difference in csPCa detection between TPB and TRB (odds ratio 1.0, 95%-confidence interval (CI) 0.62–1.76, p = 0.9; for men on active surveillance: odds ratio 1.05, 95%-CI 0.58–1.88, p = 0.9). This was confirmed in anterior and apical lesions although absolute numbers were low. TPB reduced infectious complications with fever compared to TRB (1.1% vs 5.1%, difference = 4.0%, 95%-CI 1.0–7.9, p = 0.010). Conclusions: TPB has no different csPCa detection rate from TRB taking CR/IDC into account. TPB is, however, preferable because of less infectious complications, even if AP is omitted

Serum PSA-based early detection of prostate cancer in Europe and globally: past, present and future

In the pre-PSA-detection era, a large proportion of men were diagnosed with metastatic prostate cancer and died of the disease; after the introduction of the serum PSA test, randomized controlled prostate cancer screening trials in the USA and Europe were conducted to assess the effect of PSA screening on prostate cancer mortality. Contradictory outcomes of the trials and the accompanying overdiagnosis resulted in recommendations against prostate cancer screening by organizations such as the United States Preventive Services Task Force. These recommendations were followed by a decline in PSA testing and a rise in late-stage diagnosis and prostate cancer mortality. Re-evaluation of the randomized trials, which accounted for contamination, showed that PSA-based screening does indeed reduce prostate cancer mortality; however, the debate about whether to screen or not to screen continues because of the considerable overdiagnosis that occurs using PSA-based screening. Meanwhile, awareness among the population of prostate cancer as a potentially lethal disease stimulates opportunistic screening practices that further increase overdiagnosis without the benefit of mortality reduction. However, in the past decade, new screening tools have been developed that make the classic PSA-only-based screening an outdated strategy. With improved use of PSA, in combination with age, prostate volume and with the application of prostate cancer risk calculators, a risk-adapted strategy enables improved stratification of men with prostate cancer and avoidance of unnecessary diagnostic procedures. This combination used with advanced detection techniques (such as MRI and targeted biopsy), can reduce overdiagnosis. Moreover, new biomarkers are becoming available and will enable further improvements in risk stratification