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 <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 <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.

From Screening to Mortality Reduction: An Overview of Empirical Data on the Patient Journey in European Randomized Study of Screening for Prostate Cancer Rotterdam After 21 Years of Follow-up and a Reflection on Quality of Life.

BACKGROUND: Previous research quantified the effect of prostate-specific antigen (PSA)-based prostate cancer (PCa) screening on quality-adjusted life years using 11-yr follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC) extrapolated by the Microsimulation Screening Analysis (MISCAN). ERSPC data now matured to 21 yr of follow-up. OBJECTIVE: To provide an overview of the effect of PSA-based screening on tumour characteristics and PCa treatment using long-term, detailed, empirical ERSPC data. DESIGN, SETTING, AND PARTICIPANTS: Men were included from the ERSPC Rotterdam who were randomised to a PSA-based screening (S) or control (C) arm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the effects of PSA-based screening on the number of PCa diagnoses, tumour characteristics, treatments, and cumulative incidence of disease progression. We also evaluated the changes in tumour characteristics and treatments over time for both study arms. RESULTS AND LIMITATIONS: Among PCa patients in the S-arm, fewer patients were diagnosed with advanced tumour stages (T3/T4: 12% vs 23%; relative risk [RR] = 0.50; 95% confidence interval [CI] 0.44-0.57), less disease progression was observed, and less secondary treatment (30% vs 48%; RR = 0.61; 95% CI 0.57-0.66; p < 0.001) and less palliative treatment were needed (21% vs 55%; RR = 0.38; 95% CI 0.35-0.42) than among those in the C-arm. This was at the cost of overdiagnosis and increased local treatments (eg, radical prostatectomy: 32% vs 14%; RR = 2.18; 95% CI 1.92-2.48). Over time, the number of local treatments decreased, whereas expectant management strategies increased. The RRs of treatments were slightly different from those of the MISCAN. CONCLUSIONS: After 21 yr of follow-up, empirical data of the ERSPC showed that PSA-based screening reduces advanced PCa stages, disease progression, and extensive treatments at the cost of more overdiagnosis and probably more overtreatment. Our data showed reduced local treatments and increased expectant management strategies over time. PATIENT SUMMARY: Prostate-specific antigen-based screening reduces the number of invasive prostate cancer treatments needed, however, at the cost of more overdiagnosis and probably more overtreatment. Limiting these costs remains crucial to benefit optimally from prostate cancer screening.

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 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. 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.

Active Surveillance for Prostate Cancer: Past, Current, and Future Trends.

In response to the rising incidence of indolent, low-risk prostate cancer (PCa) due to increased prostate-specific antigen (PSA) screening in the 1990s, active surveillance (AS) emerged as a treatment modality to combat overtreatment by delaying or avoiding unnecessary definitive treatment and its associated morbidity. AS consists of regular monitoring of PSA levels, digital rectal exams, medical imaging, and prostate biopsies, so that definitive treatment is only offered when deemed necessary. This paper provides a narrative review of the evolution of AS since its inception and an overview of its current landscape and challenges. Although AS was initially only performed in a study setting, numerous studies have provided evidence for the safety and efficacy of AS which has led guidelines to recommend it as a treatment option for patients with low-risk PCa. For intermediate-risk disease, AS appears to be a viable option for those with favourable clinical characteristics. Over the years, the inclusion criteria, follow-up schedule and triggers for definitive treatment have evolved based on the results of various large AS cohorts. Given the burdensome nature of repeat biopsies, risk-based dynamic monitoring may further reduce overtreatment by avoiding repeat biopsies in selected patients.

Prostate cancer risk assessment by the primary care physician and urologist: transabdominal- versus transrectal ultrasound prostate volume-based use of the Rotterdam Prostate Cancer Risk Calculator.

Background: Our objective was to assess the accuracy of transabdominal ultrasound (TAUS) measured prostate volume in the primary care setting with transrectal ultrasound (TRUS) measured prostate volume by the urologist as the reference test. Furthermore, our objective was to assess whether risk-stratification using TAUS prostate volume by the primary care physician could reduce unnecessary referrals to the urologist. Methods: Men in two Dutch primary care offices with a prostate cancer (PCa) screening request received a digital rectal examination (DRE), prostate specific-antigen (PSA), and TAUS prostate volume measurement by the general practitioner, followed by Rotterdam Prostate Cancer Risk Calculator (RPCRC) risk assessment. The examination was repeated by a urologist using TRUS. A prostate biopsy was performed in case of a RPCRC positive biopsy advice. A non-inferiority analysis was performed comparing TAUS and TRUS prostate volume differences. A risk-based referral strategy using TAUS and the RPCRC in the primary care setting was compared with the standard referral strategy based on PSA (≥3 ng/mL) and DRE. Results: A total of 105 men were included with a median PSA of 1.9 ng/mL. The mean prostate volumes measured by TAUS and TRUS were 55 and 45 mL, respectively. The mean overestimation of the prostate volume by TAUS as compared to the reference test was 9.9 mL (95% CI: 5.9-13.8). According to Dutch standard practice, 41 out of 105 (39%) men would have been referred to the urologist. Stratification in primary care based on the RPCRC using TAUS prostate volume would have avoided 29 out of the 41 (71%) referrals, at the expense of non-referral of 5 out of 11 (45%) men with a biopsy indication, according to the urologist. Conclusions: RPCRC-based risk stratification in primary care using TAUS prostate volume measurement is feasible and may prevent unnecessary referrals to the urologist and reduce costs. The accuracy of the risk assessment with TAUS might be improved by sufficient training and centralization to achieve a higher volume of consultations in primary care facilities.

Detailed Evaluation of Androgen Deprivation Overtreatment in Prostate Cancer Patients Compared to the European Association of Urology Guidelines Using Long-term Data from the European Randomised Study of Screening for Prostate Cancer Rotterdam.

Background: Guidelines on androgen deprivation therapy (ADT) for prostate cancer (PCa) arise from a critical appraisal of scientific evidence, which is a costly effort. Despite these efforts and the side effects of ADT, guidelines may not always be adhered to. Objective: To determine ADT overtreatment in PCa patients compared to the European Association of Urology (EAU) guidelines, and to identify predictors and physicians' motivations for this overtreatment. Design setting and participants: Men were included from the European Randomised study of Screening for Prostate Cancer (ERSPC) Rotterdam who were diagnosed with PCa between 2001 and 2019, and received ADT <1 yr after diagnosis. Outcome measurements and statistical analysis: Patients were categorised into the concordant ADT or discordant ADT group following the EAU guidelines. Physicians' motivations for discordancy were reported. Multivariable logistic regression was performed to identify predictors for guideline-discordant ADT including the nonlinear fit of the year of diagnosis. Results and limitations: Of 3608 PCa patients, 1037 received ADT <1 yr after diagnosis. Adherence improved gradually over the study period, resulting in overall discordancy of 15%. A patient diagnosed in 2011 had 3.3 times lower risk on guideline-discordant ADT than a patient diagnosed in 2004 (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.18-0.50). The most common reason for discordancy was unwillingness or unfitness for curative treatment of asymptomatic patients. Age (OR 1.19; 95% CI 1.15-1.24) and Gleason score ≥4 + 3 (OR 1.70; 95% CI 1.06-2.74) were associated with guideline-discordant ADT. Conclusions: In a Dutch cohort, slow adaptation of the EAU guidelines on ADT for PCa patients between 2001 and 2019 resulted in overall overtreatment of 15%, mostly in asymptomatic patients who were unfit or unwilling for curative treatment. Clear, structured presentation, or integration of these tailored guidelines into the electronic health record might accelerate the adaptation of future guidelines. Patient summary: Slow adaptation of the guidelines on hormonal therapy resulted in overtreatment in 15% of prostate cancer patients, mostly in asymptomatic patients who were unfit or unwilling for curative treatment.

Prevalence of Atopy following Mass Drug Administration with Albendazole: A Study in School Children on Flores Island, Indonesia.

BACKGROUND: In many rural areas of tropical countries such as Indonesia, the prevalence of soil-transmitted helminths (STH) infections remains high. At the same time, the burden of allergic disorders in such rural areas is reported to be low and inversely associated with helminth infections. To reduce the morbidity and transmission of helminth infections, the world health organization recommends preventive treatment of school children by providing mass drug administration (MDA) with albendazole. Here, we had an opportunity to evaluate the prevalence of skin reactivity to allergens before and after albendazole treatment to get an indication of the possible impact of MDA on allergic sensitization. METHODS: A study was conducted among 150 school children living in an area endemic for STH infections. Before and 1 year after anthelminthic treatment with albendazole, stool samples were examined for the presence of STH eggs, skin prick tests (SPT) for cockroach and house dust mites were performed, blood eosinophilia was assessed, and total immunoglobulin E (IgE) and C-reactive protein (CRP) were measured in plasma. RESULTS: Anthelminthic treatment significantly reduced the prevalence of STH from 19.6 before treatment to 6% after treatment (p < 0.001). Levels of total IgE (estimate: 0.30; 95% CI 0.22-0.42, p < 0.0001), CRP (estimate: 0.60; 95% CI 0.42-0.86, p = 0.006), and eosinophil counts (estimate: 0.70; 95% CI 0.61-0.80, p < 0.001) decreased significantly. The prevalence of SPT positivity increased from 18.7 to 32.7%. Multivariate analysis adjusted for confounding factors showed an increased risk of being SPT positive to any allergen (OR 3.04; 95% CI 1.338-6.919, p = 0.008). CONCLUSIONS: This study indicates that 1 year of MDA with albendazole was associated with a reduced prevalence of STH infections. This study shows that the prevalence of allergic sensitization increases after 1 year of albendazole treatment. Placebo-controlled and larger studies are needed to further substantiate a role of deworming treatment in an increased risk of allergic sensitization.