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Aim: The aim of this systematic review was to assess the effects on psychosocial and mental health, cognition, body composition, and metabolic markers of hormone treatment in children with gender dysphoria. Methods: Systematic review essentially follows PRISMA. We searched PubMed, EMBASE and thirteen other databases until 9 November 2021 for English‐language studies of hormone therapy in children with gender dysphoria. Of 9934 potential studies identified with abstracts reviewed, 195 were assessed in full text, and 24 were relevant. Results: In 21 studies, adolescents were given gonadotropin‐releasing hormone analogues (GnRHa) treatment. In three studies, cross‐sex hormone treatment (CSHT) was given without previous GnRHa treatment. No randomised controlled trials were identified. The few longitudinal observational studies were hampered by small numbers and high attrition rates. Hence, the long‐term effects of hormone therapy on psychosocial health could not be evaluated. Concerning bone health, GnRHa treatment delays bone maturation and bone mineral density gain, which, however, was found to partially recover during CSHT when studied at age 22 years. Conclusion: Evidence to assess the effects of hormone treatment on the above fields in children with gender dysphoria is insufficient. To improve future research, we present the GENDHOR checklist, a checklist for studies in gender dysphoria. [ABSTRACT FROM AUTHOR]

Introduction: Radiographs of the hand and teeth are frequently used for medical age assessment, as skeletal and dental maturation correlates with chronological age. These methods have been criticized for their lack of precision, and magnetic resonance imaging (MRI) of the knee has been proposed as a more accurate method. The aim of this systematic review is to explore the scientific and statistical evidence for medical age estimation based on skeletal maturation as assessed by MRI of the knee. Materials and methods: A systematic review was conducted that included studies published before April 2021 on living individuals between 8 and 30 years old, with presumptively healthy knees for whom the ossification stages had been evaluated using MRI. The correlation between "mature knee" and chronological age and the risk of misclassifying a child as an adult and vice versa was calculated. Results: We found a considerable heterogeneity in the published studies —in terms of study population, MRI protocols, and grading systems used. There is a wide variation in the correlation between maturation stage and chronological age. Conclusion: Data from published literature is deemed too heterogenous to support the use of MRI of the knee for chronological age determination. Further, it is not possible to assess the sensitivity, specificity, negative predictive value, or positive predictive value for the ability of MRI to determine whether a person is over or under 18 years old. Key Points: • There is an insufficient scientific basis for the use of magnetic resonance imaging of the knee in age determination by skeleton. • It is not possible to assess the predictive value of MRI of the knee to determine whether a person is over or under 18 years of age. [ABSTRACT FROM AUTHOR]

The European Randomized study of Screening for Prostate Cancer (ERSPC) has shown a 20% relative reduction in prostate cancer mortality after 16 yr [rate ratio (RR) 0.80], but centers varied by attendance, screen interval, biopsy compliance, contamination in the control arm, and treatments. We used a microsimulation model, calibrated to the ERSPC individual-level data, to predict influence of study features on the results. The relative reduction in prostate cancer mortality would have been somewhat larger with improved study features: increased attendance (90% attendance in all volunteer-based and 70% in all population-based centers, resulting in RR 0.77), a 2-yr screen interval (RR 0.75), and an 80% biopsy compliance (RR 0.79). The RR would have been substantially lower with a 30% attendance (RR 0.92), 40% biopsy compliance (RR 0.90), or 100% contamination (RR 0.85). The variations in results by trial center may reflect differences in study design and performance and results of our simulations highlight the effect of quality indicators in prostate-specific antigen screening in different settings. We evaluated the effect of various features of prostate-specific antigen (PSA) screening on its effectiveness. The compliance to PSA testing and those having a biopsy after an elevated PSA substantially influence the prostate cancer mortality. The prostate cancer mortality reduction found in the European Randomized study of Screening for Prostate Cancer (ERSPC) is close to what would have been expected when all centers would have performed as the best performing center. [ABSTRACT FROM AUTHOR]

Aims: The reported long waiting times for cancer patients have mostly been related to prognostic outcome and less to patient-related experience to outcome. We assessed waiting times for patients with cancer of the breast, prostate, colon or rectum in Sweden. Methods: The median time from referral to start of treatment was assessed using data from clinical cancer registers for patients who received curative treatment during 2011, 2012 and 2013. Results: The median overall waiting time in different counties ranged from 7 to 28 days for breast cancer, from 117 to 280 days for prostate cancer, from 27 to 64 days for colon cancer and from 48 to 80 days for rectal cancer. For the entire nation, the median time from referral to start of treatment remained unchanged from 2011 to 2013 for each cancer diagnosis. Conclusions: Large variations were found in waiting times between different counties in Sweden and between different types of cancer. The long waiting times identified in this study emphasize the need to improve national programmes for more rapid diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone.Methods: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50-69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406.Findings: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (p<0·0001), the area under the curve was 0·56 (95% CI 0·55-0·60) with PSA alone and 0·74 (95% CI 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (p<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of ≥3 ng/mL to diagnose high risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI 24-39) and could avoid 44% (35-54) of benign biopsies.Interpretation: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes.Funding: Stockholm County Council (Stockholms Läns Landsting). [ABSTRACT FROM AUTHOR]

Despite limited scientific support, a repeat prostate-specific antigen (PSA) test before prostate biopsy decisions is common. We analyzed biopsy outcomes in 1686 men from the STHLM3 study with PSA 3-10 ng/mL and two PSA tests taken within eight weeks and before prostate biopsy using percentages and multinomial logistic regression. We found that omitting prostate biopsy for men with PSA values decreasing to PSAs of 3 ng/mL or less would save 16.8% of biopsy procedures, while missing 5.4% of the cancers with Gleason scores (GSs) of 7 or higher. The proportion of cancers with GSs of 6 or lower was independent of the first PSA value, as well as of PSA change. Also, the risk of tumors with GSs of 7 or higher decreased with both decreasing and increasing PSA levels: It was 18.6% (95% confidence interval [CI] = 16.3% to 20.9%) for men with PSA changes of less than 20%, 12.1% (95% CI = 8.0% to 16.2%) for men with PSA levels increasing at least 20%, and 6.6% (95% CI = 3.8% to 9.3%) for men with PSA levels decreasing at least 20%. [ABSTRACT FROM AUTHOR]

Background Family history is a strong risk factor for prostate cancer. The aim of this study was to investigate whether increased diagnostic activity is related to the incidence of prostate cancer among brothers of men with prostate cancer. Methods Data were from the nationwide population-based Prostate Cancer Database Sweden (PCBaSe Sweden), which includes data from the National Prostate Cancer Register, the Swedish Cancer Register, the Register of the Total Population, the Multi-Generation Register, and the Census database. We investigated the relationship of tumor characteristics, time from diagnosis of the index patient (ie, prostate cancer patients in the National Prostate Cancer Register for whom at least one brother and their father could be identified), calendar period, geographic factors, and socioeconomic status to standardized incidence ratios (SIRs) for prostate cancer among 22 511 brothers of 13 975 index patients in PCBaSe Sweden. Results Brothers of index patients with prostate cancer were at increased risk for a diagnosis of prostate cancer (SIR = 3.1, 95% confidence interval [CI] = 2.9 to 3.3). Risk was higher for T1c tumors (SIR = 3.4, 95% CI = 3.2 to 3.8) than for metastatic tumors (SIR = 2.0, 95% CI = 1.5 to 2.6), and risk of T1c tumors was especially high during the first year after the diagnosis of the index patient (SIR = 4.3, 95% CI = 3.8 to 4.9), compared with the following years (SIR range = 2.8-3.3), and for brothers of index patients who had a higher socioeconomic status (SIR = 4.2, 95% CI = 3.7 to 4.7), compared with brothers of index patients with lower socioeconomic status (SIR = 2.8, 95% CI = 2.4 to 3.2). Conclusions Increased diagnostic activity among men with a family history of prostate cancer appears to contribute to their increased risk of prostate cancer and to lead to detection bias in epidemiological and genetic studies of familial prostate cancer. [ABSTRACT FROM AUTHOR]

Summary: Background: Cancer is associated with an increased risk of thromboembolic diseases, but data on the association between prostate cancer and thromboembolic diseases are scarce. We investigated the risk of thromboembolic disease in men with prostate cancer who were receiving endocrine treatment, curative treatment, or surveillance. Methods: We analysed data from PCBaSe Sweden, a database based on the National Prostate Cancer Register, which covers over 96% of prostate cancer cases in Sweden. Standardised incidence ratios (SIR) of deep-venous thrombosis (DVT), pulmonary embolism, and arterial embolism were calculated by comparing observed and expected (using the total Swedish male population) occurrences of thromboembolic disease, taking into account age, calendar-time, number of thromboembolic diseases, and time since previous thromboembolic disease. Findings: Between Jan 1, 1997, and Dec 31, 2007, 30 642 men received primary endocrine therapy, 26 432 curative treatment, and 19 526 surveillance. 1881 developed a thromboembolic disease. For men on endocrine therapy, risks for DVT (SIR 2·48, 95% CI 2·25–2·73) and pulmonary embolism (1·95, 1·81–2·15) were increased, although this was not the case for arterial embolism (1·00, 0·82–1·20). Similar patterns were seen for men who received curative treatment (DVT: 1·73, 1·47–2·01; pulmonary embolism: 2·03, 1·79–2·30; arterial embolism: 0·95, 0·69–1·27) and men who were on surveillance (DVT: 1·27, 1·08–1·47; pulmonary embolism: 1·57, 1·38–1·78; arterial embolism: 1·08, 0·87–1·33). Increased risks for thromboembolic disease were maintained when patients were stratified by age and tumour stage. Interpretation: All men with prostate cancer were at higher risk of thromboembolic diseases, with the highest risk for those on endocrine therapy. Our results indicate that prostate cancer itself, prostate cancer treatments, and selection mechanisms all contribute to increased risk of thromboembolic disease. Thromboembolic disease should be a concern when managing patients with prostate cancer. Funding: Swedish Research Council, Stockholm Cancer Society, and Cancer Research UK. [Copyright &y& Elsevier]

Objective. The incidence of prostate cancer in Sweden is increasing rapidly, as is treatment with curative intent. Radical prostatectomy (RP) is currently commonly performed, either within or outside large high-volume centres. The aim of this study was to assess the 30-day mortality rate after RP in Sweden. Material and methods. In this nationwide population-based study, all men diagnosed with localized prostate cancer (≤70 years, clinical stadium T1–2, prostate-specific antigen <20 ng/ml) who underwent RP in Sweden between 1997 and 2002 were identified through the National Prostate Cancer Register (NPCR). Mortality within 30 days of RP was analysed through linkage between the follow-up study of the NPCR and the Regional Population Registers. The cause of death in the death certificates were compared with data from the hospitals concerned. To validate the results, a record linkage between the Inpatient Register and the National Population Register was also performed. Results. The number of RPs performed increased over time. Among 3700 RPs performed, four deaths occurred during the first 30 days, yielding a 0.11% 30-day mortality rate. These deaths occurred at three different types of hospital and were all probably related to the RP. Conclusion. This study provides further evidence that RP is a procedure with very low perioperative mortality even when performed outside high-volume centres. [ABSTRACT FROM AUTHOR]

The article discusses the concept of natural history of prostate cancer. It is completely untreated can only be assessed in series of patients before the mid-20th century. The present natural history of early prostate cancer can best be described from published series of watchful waiting and active surveillance. The outcome of watchful waiting in conservative management is highly related to the tumour grade and it was shown that patients with low-grade tumours seldom die from prostate cancer.

Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer [ABSTRACT FROM AUTHOR]

Abstract: Objective: This observational cohort study describes the long-term outcome of patients with clinically localized prostate cancer managed with watchful waiting, the prognostic value of tumour ploidy, and the impact of comorbidity. Methods: A total of 119 patients with clinically localized (T1–2) prostate cancer consecutively diagnosed from 1978 to 1982 were prospectively managed by watchful waiting, with treatment given if progression occurred. Results: Median age was 68 yr. Median observation time was 24 yr±6.25 (SD). Of the 112 patients who died, 42 died of prostate cancer. Disease-specific survival rates were 85% (95% CI: 77–93%), 58% (46–70%), and 32% (19–46%) at 10, 15, and 20 yr, respectively. Treatment-free survival rate was 43% (95% CI: 33–54%) at 10 yr. Patients aged 70 yr and over had a statistically significant increased risk of dying from any cause. There was a statistically significant increased risk of dying from prostate cancer for patients with nondiploid tumours. Conclusion: In the present series from the pre-PSA era, watchful waiting yielded a relatively high long-term disease-specific survival rate in patients with well- or moderately differentiated clinically localized prostate cancer, and almost half were not treated 10 yr after diagnosis. Watchful waiting may be an option at least for such patients with a 10- to 15-yr life expectancy. Age of 70 yr or more predicted an increased overall mortality. High comorbidity increased the risk (although not statistically significant) for death from any cause and for death from prostate cancer. Patients with nondiploid tumours were at an increased risk to die from prostate cancer. [Copyright &y& Elsevier]

Abstract: Objectives: A patient with newly diagnosed localized prostate cancer can choose from an array of therapies. A patient''s willingness to trade life for freedom from therapy-induced long-term symptoms is poorly investigated. Methods: In October 2002, we attempted to collect information from the 591 men who had been diagnosed and registered with prostate cancer in 1999 in Stockholm County. In a postal questionnaire, men were asked to balance absence or presence of certain therapy-induced long-term symptoms against varying lengths of survival gain as a consequence of the therapy. Results: Information was provided by 511 (86%) of the 591 men. A large majority of the men participating in this study ended up in one of two extreme categories: either they accepted the therapy-induced symptom to gain survival or they did not. For fecal leakage, 78% of the men chose one of two extreme categories compared with 74% for urinary leakage, 71% for tender enlarged breasts, 73% for erectile dysfunction, and 78% for restricted diet. Thirty-seven percent of the men in the study were willing to accept fecal leakage if there was only the slightest chance to gain survival, comparing percentages for urinary leakage, tender enlarged breasts, restricted diet, and erectile dysfunction and were 48%, 53%, 55%, and 64%, respectively. Conclusion: Willingness to accept therapy-induced long-term symptoms to avoid a shortened survival due to prostate cancer varies dramatically among men with localized prostate cancer and a large majority of men are in one of two extreme categories. Among symptoms, long-term fecal leakage was the one fewest men were willing to accept to gain survival. [Copyright &y& Elsevier]

Substantial gaps exist in the data of the assessment of risk and prognosis that limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic, prostate cancer, of our time. This report was prepared by an international multidisciplinary committee of the World Health Organization to address contemporary issues of epidemiology and statistical methods in prostate cancer, including a summary of current risk assessment methods and prognostic factors. Emphasis was placed on the relative merits of each of the statistical methods available. We concluded that: An international committee should be created to guide the assessment and validation of molecular biomarkers. The goal is to achieve more precise identification of those who would benefit from treatment. Prostate cancer is a predictable disease despite its biologic heterogeneity. However, the accuracy of predicting it must be improved. We expect that more precise statistical methods will supplant the current staging system. The simplicity and intuitive ease of using the current staging system must be balanced against the serious compromise in accuracy for the individual patient. The most useful new statistical approaches will integrate molecular biomarkers with existing prognostic factors to predict conditional life expectancy (i.e. the expected remaining years of a patient's life) and take into account all-cause mortality. [ABSTRACT FROM AUTHOR]

Substantial gaps exist in the data of the assessment of risk and prognosis that limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic, prostate cancer, of our time. This report was prepared by an international multidisciplinary committee of the World Health Organization to address contemporary issues of epidemiology and statistical methods in prostate cancer, including a summary of current risk assessment methods and prognostic factors. Emphasis was placed on the relative merits of each of the statistical methods available. We concluded that: An international committee should be created to guide the assessment and validation of molecular biomarkers. The goal is to achieve more precise identification of those who would benefit from treatment. Prostate cancer is a predictable disease despite its biologic heterogeneity. However, the accuracy of predicting it must be improved. We expect that more precise statistical methods will supplant the current staging system. The simplicity and intuitive ease of using the current staging system must be balanced against the serious compromise in accuracy for the individual patient. The most useful new statistical approaches will integrate molecular biomarkers with existing prognostic factors to predict conditional life expectancy (i.e. the expected remaining years of a patient's life) and take into account all-cause mortality. [ABSTRACT FROM AUTHOR]

Presents a guideline for the clinical management of prostatic intraepithelial neoplasia (PIN). Patients eligible for curative treatment of prostate cancer; Features of biopsies needing repeat biopsies; Use of core biopsies for adequate diagnosis of PIN.

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87–0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81–0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa. [ABSTRACT FROM AUTHOR]

Examines sexual desire, erection, orgasm and ejaculatory function among elderly Swedish men. Extent to which the sexual function is intact; Compulsory sex education in schools; Importance of maintaining the sexual function.

An introduction to the journal is presented in which the editor discusses the issue of prostate cancer screening and the article by Hans-Olov Adami "The prostate cancer pseudo-epidemic" contained within the issue.

This secondary analysis of a randomized clinical trial assesses whether screening for prostate-specific antigen reduces prostate cancer mortality at 15-year follow-up. Key Points: Question: In men aged 50 to 69 years, does a single invitation for a prostate-specific antigen (PSA) screening test reduce prostate cancer mortality at 15-year follow-up compared with no invitation for testing? Findings: In this secondary analysis of a randomized clinical trial of 415 357 men aged 50 to 69 years randomized to a single invitation for PSA screening (n = 195 912) or a control group without PSA screening (n = 219 445) and followed up for a median of 15 years, risk of death from prostate cancer was lower in the group invited to screening (0.69% vs 0.78%; mean difference, 0.09%) compared with the control group. Meaning: Compared with no invitation for routine PSA testing, a single invitation for a PSA screening test reduced prostate cancer mortality at a median follow-up of 15 years, but the absolute mortality benefit was small. Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. Objective: To evaluate the effect of a single invitation for PSA screening on prostate cancer–specific mortality at a median 15-year follow-up compared with no invitation for screening. Design, Setting, and Participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Intervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). Main Outcomes and Measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer–specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Results: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P =.03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P <.001) and localized (T1/T2: 3.6% vs 3.1%; P <.001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P =.11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. Trial Registration: isrctn.org Identifier: ISRCTN92187251 [ABSTRACT FROM AUTHOR]

Abstract Background Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias. Objective To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study. Design, setting, and participants Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT). Outcome measures and statistical methods Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses. Results and limitations Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20–1.44). Conclusions Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment. Patient summary Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy. Take Home Message The increase in overall comorbidity following androgen androgen deprivation therapy for advanced prostate cancer was significantly higher for gonadotrophin gonadotrophin-releasing hormone agonists than for anti-androgen (AA) monotherapy. More consideration should be given to AA monotherapy as an alternative first-line therapy. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Role of Fear in Overdiagnosis and Overtreatment--An Essay" in the October 24, 2014 issue is presented.

Background: Implementation of risk-based prostate cancer screening has been proposed as a means to reduce the harms of PSA screening. Little is known, however, about the factors influencing men’s decision to attend a prostate cancer screening based on a risk assessment. Method: We sent postal invitations with a login to a survey to 10.000 men, three months before invitation to a risk-based prostate cancer screening. Prostate cancer specific worry, prostate cancer-related knowledge, health behaviour, and health related quality of life were used as predictors of subsequent participation. Participation to risk-based prostate cancer screening was defined as providing a blood sample for the STHLM3 trial, a study evaluating a risk-based model that predicts the risk for aggressive prostate cancer. Results: With a response rate of 20%, 1.347 men (70%) participated in ensuing risk-based prostate cancer screening three months later whereas 568 men (30%) declined participation in the STHLM3-study. These decliners reported less worry and feeling less vulnerable to prostate cancer and responded “Do not know” more often than participants when asked questions about prostate cancer knowledge. Participants reported greater benefits of prostate testing (p = 0.0005), less barriers to prostate testing (p<0.0001), and higher intention to attend prostate cancer testing (p<0.0001) than decliners. Finally, participants reported better overall health than decliners (p<0.0001). Conclusion: Prostate cancer worry, PC knowledge, health behaviour and quality of life were identified as predictors of participation in risk-based prostate cancer screening. Targeting these predictors may improve the participation rates. These results can inform policymaking for future population-based prostate cancer screening programs that should address potential worry in men and lack of knowledge about prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Improving participation rates in epidemiologic studies using questionnaires and biological sampling is important for the generalizability of the outcome. The aim of this study was to examine the effects of pre-notification, invitation length, questionnaire length, and reminder on participation rate and to investigate whether some factors contributed to participants doing both the questionnaire and blood sampling as oppose to only one part.Methods: Our study was embedded within the pilot testing of a large population-based study about prostate cancer screening. Our study sample consisted of 28.134 men between 50 and 69 years of age and living in the region of Stockholm (Sweden) invited to respond to a web-based questionnaire and to provide blood for prostate cancer testing. The men were randomly allocated according to birth of date to receive either: (a) a pre-notification postcard or not; (b) a shorter or a longer invitation letter; (c) a shorter or a longer web-based questionnaire, and (d) a reminder or not. The effects of the survey design factors were tested using chi-square.Results: The use of a pre-notification (p < 0.0001), a longer questionnaire (p = 0.004) and the use of a reminder (p = 0.02) were associated with an increase in overall participation, i.e. responding to the questionnaire or providing blood for PCT or performing both components.Conclusions: The results of this pilot study justified the use of a pre-notification and a reminder in the following large population based study since the benefits of increased participation traded off against the greater costs incurred. Furthermore, we were able to use the longer version of the questionnaire, which allowed us to collect more information without risking a lower response rate. [ABSTRACT FROM AUTHOR]

The authors discuss safety issues in the modern treatment for cervical pre-cancer, particularly cervical intraepithelial neoplasia (CIN). They present two studies that analyzed the possible harms to human reproduction of the CIN treatments, particularly on fertility. Also examined is the possibility that human papillomavirus infection contributes to the development of preterm labour.

Patients with head and neck (H&N) cancer are commonly treated with surgery and/or radiotherapy, which can increase the risk of oral infection, dental caries, and periodontal disease. The present study investigated dental care consumption and costs in patient with H&N cancer before and after the cancer diagnosis. Data from Swedish regional and national registers were used to follow up dental care utilization and dental procedure costs. The analysis included 2,754 patients who had been diagnosed with H&N cancer (exposed cohort) in Stockholm County, Sweden, during 2000–2012 and 13,036 matched persons without cancer (unexposed cohort). The exposed cohort was sub-grouped into irradiated and non-irradiated patients for analysis. The exposed cohort underwent a moderately higher number of dental procedures per year than the unexposed cohort in both the year of the cancer diagnosis and the year after cancer diagnosis; in addition, these numbers were higher in the irradiated than in the non-irradiated subgroup of the exposed cohort. Dental care consumption and costs in the exposed cohort declined over time but remained at a slightly higher level than in the unexposed cohort over the long term (more than two years). Examinations and preventive procedures accounted for most of the higher consumption in the short term (2 years) and at the longer term follow-up. Swedish national insurance subsidized costs for dental treatment, which were highest in the irradiated subgroup and lowest in the unexposed cohort. Direct costs to the patient, however, were similar among the groups. Swedish national health insurance protects patients with H&N cancer from high dental expenditures. Further studies on the cost-effectiveness of preventive dental care for patients are needed. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa).Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age- and county-matched comparison cohort of PCa-free men (n=46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression.Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis.Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED. [ABSTRACT FROM AUTHOR]

Background: Gonadotropin-releasing hormone agonists (GnRH) used in prostate cancer (PCa) are associated with atherogenic dyslipidaemia. It can be assumed that GnRH need to be used with greater caution in men with type 2 diabetes mellitus (T2DM). This study investigated association of GnRH with atherogenic lipids (AL) in PCa men with T2DM. Methods: Two cohorts including 38,311 men with 11 years follow-up based on Swedish national registers were defined (PCa-Exposure cohort and GnRH-Exposure cohort). Based on European guidelines on cardiovascular diseases (CVD), primary outcomes were defined as: 1.0 mmol/L increase in AL and lipid-lowering therapy (LLT) intensification. We used Cox proportional-hazards models and Kaplan–Meier curves to assess the association. Results: There was an association between GnRH and increased AL (i.e., triglyceride, PCa-Exposure cohort: HR 1.77, 95% CI 1.48–2.10; GnRH-Exposure cohort: HR 1.88, 95% CI 1.38–2.57). There was also an association between PCa diagnosis and increased AL. In contrast, no association between LLT intensification and GnRH was found. Conclusion: In this large population-based study, men with T2DM on GnRH for PCa had an increased risk of increased atherogenic lipids. These results highlight the need to closely monitor lipids and to be ready to intensify lipid-lowering therapy in men with T2DM on GnRH for PCa. [ABSTRACT FROM AUTHOR]

The author reflects on the increase in the impact factor of the "Scandinavian Journal of Urology and Nephrology." He relates that the impact factor is the measure of the usage of the journal, it helps increase the prestige of the journal, and increases the chance of receiving research grants. Moreover, he stresses that it is important for members to use the journal and cites information published in the journal in order to maintain the journal's good standing in the impact factor.

Editorial. Announces the retirement of Mattias Aurell as nephrological editor of the periodical 'Scandinavian Journal of Urology and Nephrology.' His influence on the nephrological content of the periodical; Percentage of manuscripts on nephrology submitted to the periodical.

Editorial. Focuses on the developments of the Scandinavian Journal of Urology and Nephrology in 2000 to 2001. Percentage increase of the impact factor of the journal; Reduction in the handling times of manuscripts in the editorial office; Accessibility of the journal in the internet and to the members of the Scandinavian Association of Urology.

Objective To detail the distribution of causes of death from localized prostate cancer ( PCa). Patients and Methods The database PCBase Sweden links the Swedish National Prostate Cancer Register with other nationwide population-based healthcare registers. We selected all 57 187 men diagnosed with localized PCa between 1997 and 2009 and their 114 374 PCa-free control subjects, matched according to age and county of residence. Mortality was calculated using competing risk regression analyses, taking into account PCa risk category, age and Charlson comorbidity index ( CCI). Results In men with low-risk PCa, all-cause mortality was lower compared with that in corresponding PCa-free men: 10-year all-cause mortality was 18% for men diagnosed at age 70 years, with a CCI score of 0, and 21% among corresponding control subjects. Of these cases, 31% died from cardiovascular disease ( CVD) compared with 37% of the corresponding control subjects. For men with low-risk PCa, 10-year PCa-mortality was 0.4, 1 and 3% when diagnosed at age 50, 60 and 70 years, respectively. PCa was the third most common cause of death (18%), after CVD (31%) and other cancers (30%). By contrast, PCa was the most common cause of death in men with intermediate- and high-risk localized PCa. Conclusions Men with low-risk PCa had lower all-cause mortality than PCa-free men because of lower CVD mortality, driven by early detection selection; however, for men with intermediate- or high-risk disease, the rate of PCa death was substantial, irrespective of CCI score, and this was even more pronounced for those diagnosed at age 50 or 60 years. [ABSTRACT FROM AUTHOR]

Background: No meta-analysis is yet available for the risk of metabolic syndrome (MetS) following androgen deprivation therapy (ADT) for men with prostate cancer. To summarize the evidence for the link between ADT and MetS or its components quantitatively with a meta-analysis including all studies published to date. Methods: PubMed and Embase were searched using predefined inclusion criteria to perform meta-analyses on the association between metabolic syndrome, hyperglycemia, diabetes, hypertension, dyslipidemia or obesity and androgen deprivation therapy in patients with prostate cancer. Random effects methods were used to estimate pooled relative risks (RRs) and 95% confidence intervals (CI). Results: A total of nine studies was included. There was a positive association between ADT and risk of MetS (RR: 1.75 (95% CI: 1.27–2.41)). Diabetes was the only MetS component present in more than 3 studies, and also showed an increased risk following ADT (RR: 1.36 (95% CI: 1.17–1.58)). Conclusion: This is the first quantitative summary addressing the potential risk of MetS following ADT in men with PCa. The positive RRs indicate that there is a need to further elucidate how type and duration of ADT affect these increased risks of MetS and diabetes as the number of men with PCa treated with ADT is increasing. [ABSTRACT FROM AUTHOR]

Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3–6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4–6.7) for PSA > 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0–5.5). Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Methods and materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1–2, N0–NX, M0–MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. Results: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0–12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2–11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. [Copyright &y& Elsevier]

Extension of the Checklist to QAI We created an extension of the GDC to ensure that guideline developers optimally integrate QAI into guideline development (Table). Practice guidelines and quality assurance and improvement (QAI) schemes are 2 sides of the same coin for improving health outcomes ([1]). [Extracted from the article]

Abstract: Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Methods and materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1–2, N0–NX, M0–MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. Results: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0–12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2–11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment. Objective: To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent. Design, setting, and participants: We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis. Measurements: We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics. Results and limitations: The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA<4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status. Conclusions: The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors. [Copyright &y& Elsevier]

Objective. To investigate the effects of prostate-specific antigen (PSA) testing of men without clinical signs of prostate cancer on the incidence of prostate cancer in Sweden. Material and methods. Information on the cause of diagnosis, tumour characteristics and primary treatment for patients diagnosed with prostate cancer between January 1999 and December 2007 was extracted from the National Prostate Cancer Register of Sweden. This register includes data for 95% of Swedish prostate cancer cases. Results. The total age-standardized annual incidence of prostate cancer per 100 000 men increased from 187 in 1999 to 233 in 2004, but decreased thereafter to 196 in 2007. The incidence of asymptomatic cases also peaked in 2004 (at 62 per 100 000 men), but varied six-fold between different counties in that year (16-98 per 100 000 men). Asymptomatic cases ( n = 17 143) constituted 15% of all new cases in 2000 and 30% in 2007. Almost as many cases were diagnosed in stage T1c in men with symptoms, usually from the lower urinary tract. Together these two groups constituted 29% of all new cases in 2000 and 52% in 2007. It was estimated that at least one-third of all Swedish men aged 50-75 years had a PSA test between 2000 and 2007. Conclusions. Even though screening for prostate cancer is not recommended in Sweden, PSA testing of men without clinical signs of prostate cancer is common. The effects on the Swedish incidence of prostate cancer were similar to those reported from the USA. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at the 2008 International Consultation "Bladder Cancer - From Pathogenesis to Prevention." Topics include the epidemiology and etiology of bladder cancer, screening and prevention of bladder cancer, and histopathological and clinical presentation of bladder urothelial carcinoma. The meeting features Jan Adolfsson, Ziya Kirkali and Paolo Boffetta.

Abstract: Aim: This study aims to determine the predictors for the symptomatic prostate cancer patient’s delays in seeking care. Methods: We followed a cohort of 931 men with prostate cancer from Stockholm County (Sweden) asking about socio-demographic and information-level characteristics as well as the length of delay in seeking care. Results: Of the 511 patients who returned a completed questionnaire, 219 (43%) reported having clinical symptoms before prostate cancer was diagnosed. Of all men with clinical symptoms, self-employed men were more likely to make an early first contact with the health-care system than pensioners or men with other employment (relative risk (RR), 3.9; 95% confidence interval (CI), 1.4–11.0). Men who had obtained moderate or much information from the internet about prostate cancer were more likely to have made an early first contact with the health-care system (RR, 2.2; 95% CI, 1.3–3.9). Men who had obtained moderate or much information from health-care staff (RR, 1.4; 95% CI, 1.0–1.6), or from any doctor (RR, 1.4; 95% CI, 1.0–1.8) or from family members/acquaintances (RR, 1.3; 95% CI, 1.0–1.9) had an early first visit to the health-care system. Men who were 70 to 80 years old started treatment earlier than men who were 50 to 69 years old (RR, 2.3; 95% CI, 1.4–3.6). Conclusions: The patients’ level of information about prostate cancer obtained from the internet and other sources such as the health-care system, doctors or family members/acquaintances coupled with their employment status were influential in leading to early first contact and first visit to the health-care system. Older patients started treatment earlier than younger patients. [Copyright &y& Elsevier]