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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]

Background: Prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood.Methods: To assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.1.Results: Overall, a decreased risk of PCa was observed for men with T2DM (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.78-0.84), as compared to men without T2DM. The decreased risk of PCa was consistently showed across duration of T2DM. With respect to use of antidiabetic drugs, this inverse association with duration was also found for all medications types, as compared to men without T2DM, including insulin, metformin and sulphonylurea (SU) (e.g. 3- < 5 yr insulin OR:0.69, 95%CI:0.60-0.80; 3- < 5 yr metformin OR: 0.82, 95%CI: 0.74-0.91; 3- < 5 yr SU OR: 0.72, 95%CI: 0.62-0.83). When stratifying by PCa risk categories, this decreased risk was most evident for diagnosis of low and intermediate-risk PCa (low-risk OR: 0.65, 95%CI: 0.66-0.70, intermediate-risk OR: 0.80, 95%CI: 0.75-0.85).Conclusions: The study showed an inverse association between pre-existing T2DM and PCa across different durations of T2DM and all types of T2DM medication received. This inverse association was most evident for low- and intermediate-risk PCa, suggesting that whilst T2DM and its medication may protect some men from developing PCa, the relationship warrants further study. [ABSTRACT FROM AUTHOR]

Aim: Gonadotropin-releasing hormone (GnRH) agonists are used to treat men with prostate cancer (PCa). To date, no study has fully assessed patterns of adherence to GnRH agonists. We investigated patterns of adherence to GnRH agonists using data from Prostate Cancer data Base Sweden (PCBaSe). Methods: PCBaSe links the National Prostate Cancer Register (NPCR) Sweden to other healthcare registers and demographic databases. Men on primary or secondary GnRH agonists between 2006–2013 entered the study 45 days after GnRH agonists' initiation (run-in period) and exited at 3 years. Medication possession ratio quantified adherents (≥80%). Multivariable logistic regression models included age, injection interval, PCa risk categories, Charlson Comorbidity Index, prior PCa treatment, civil status and year of GnRH initiation. Odds ratios (OR) and 95% confidence intervals (CI) expressed odds of adherence. Results: Men on primary GnRH agonists (n = 8,105) were more adherent with increasing age (75–84 years compared to ≤65 years OR: 1.49; 95% CI: 1.23–1.81), longer injection intervals (365 days compared to 90 days OR: 3.29; 95% CI: 2.52–4.30) and higher PCa risk categories at diagnosis (distant metastasis compared to low risk PCa OR: 3.56; 95% CI: 2.54–5.00). Men on secondary GnRH agonists (n = 4,738) were more adherent with increasing age (≥85 years compared to ≤65 years OR: 1.65; 95% CI: 1.23–2.22) and prior PCa treatment (anti-androgens compared to deferred treatment OR: 1.50; 95% CI: 1.23–1.82), (radiotherapy compared to deferred treatment OR: 1.35; 95% CI: 1.11–1.64). Conclusions: Longer injection intervals could be addressed in the clinical setting to improve adherence. [ABSTRACT FROM AUTHOR]

Background: Multi-step testing might enhance performance of the prostate cancer diagnostic pipeline. Using PSA >1 ng/ml for first-line risk stratification and the Stockholm 3 Model (S3M) blood-test >10% risk of Gleason Score > 7 prostate cancer to inform biopsy decisions has been suggested. We aimed to determine the effects of changing the PSA cutoff to perform reflex testing with S3M and the subsequent S3M cutoff to recommend prostate biopsy while maintaining the sensitivity to detect Gleason Score ≥ 7 prostate cancer.Methods: We used data from the prospective, population-based, paired, diagnostic Stockholm 3 (STHLM3) study with participants invited by date of birth from the Swedish Population Register during 2012-2014. All participants underwent testing with PSA and S3M (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms, and clinical variables [age, family, history, previous prostate biopsy, prostate exam]). Of 47,688 men in the STHLM3 main study, we used data from 3133 men with S3M >10% and prostate biopsy data. Logistic regression models were used to calculate prostate cancer detection rates and proportion saved biopsies.Results: 44.2%, 62.5% and 67.9% of the participants had PSA <1, <1.5 and <1.7 ng/ml, respectively. Increasing the PSA cut-off for additional work-up from 1 ng/ml to 1.5 ng/ml would thus save 18.3% of the performed tests, 4.9% of the biopsies and 1.3% (10/765) of Gleason Grade ≥ 7 cancers would be un-detected. By lowering the S3M cutoff to recommend biopsy, sensitivity to high-grade prostate cancer can be restored, to the cost of increasing the number of performed biopsies modestly.Conclusion: The sensitivity to detect prostate cancer can be maintained when using different PSA cutoffs to perform additional testing. Biomarker cut-offs have implications on number of tests and prostate biopsies performed. A PSA cutoff of 1.5 ng/ml to perform additional testing such as the S3M test might be considered.Trial Registration: ISRCTN84445406 . [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]

Objective. Tumour characteristics, preoperative work-up and surgical treatment in patients diagnosed with renal cell carcinoma (RCC) between 2005 and 2010, and changes over time were studied in a national population-based cohort. Material and methods. The National Swedish Kidney Cancer Register (NSKCR) contains information on histopathology, Fuhrman grade and clinical stage at presentation, and on the preoperative work-up and surgical treatment of patients with RCC. Between 2005 and 2010, 5553 RCC patients were registered in the NSKCR, 99% of those registered in the National Cancer Registry. Results. During the study period the mean tumour size decreased from 70 to 64 mm ( p = 0.024) and the frequency of metastatic RCC decreased from 22% to 15% ( p < 0.001). The use of preoperative chest computed tomography increased from 59% to 84%. In total, 4229 (76%) patients were treated with curative intent, 3453 (82%) underwent radical nephrectomy, 606 (14%) partial nephrectomy (PN) and 170 (4%) cryotherapy or radiofrequency ablation. In tumours up to 4 cm, PN was performed in 33% of the surgically treated patients. PN irrespective of size increased from 8% to 20% and laparoscopic nephrectomy increased from 6% to 17% during the period. In patients with metastatic RCC, 55% underwent cytoreductive nephrectomy. Conclusions. The NSKCR explores population-based data on the clinical handling of patients with RCC. This study, between 2005 and 2010, shows significant decrease in tumour size and metastatic RCC at presentation, a more complete preoperative work-up, and significantly increased use of PN and laparoscopic nephrectomy in Sweden. [ABSTRACT FROM AUTHOR]

Objective To evaluate the risk of different in-hospital complications for patients undergoing a radical cystectomy ( RC), as limited nationwide population data on short- and long-term complications after RC is available, despite it being the standard treatment for localised muscle-invasive urinary bladder cancer ( UBC)., Patients and Methods In all, 7608 persons underwent a RC after UBC diagnosis, as registered in the Swedish National Patient Register between 1964 and 2008., We estimated the frequency and incidences and calculated hazard ratios ( HR) and 95% confidence intervals ( CI) using multivariate Cox proportional hazards models., Results Urinary tract infection/septicaemia was the most common complication following radical cystectomy, with an incidence of 90.4 per 1,000 person years., There was a higher risk of urinary tract infection among patients who had a continent cutaneous reservoir ( HR: 1.11 (0.94-1.30) or orthotopic neobladder 1.21 (1.05-1.39) than among those with ileal conduit., Similarly, continent cutaneous reservoir and orthotopic neobladder were associated with increased risks for wound and abdominal wall hernias, stones in the urinary tract, hydronephrosis and nephrostomy tube treatment, and kidney failure., In contrast, risk of bowel obstruction was lower among those with orthotopic neobladder than those with ileal conduit ( HR: 0.64 (0.50-0.81)) and those with continent cutaneous reservoir ( HR: 0.92 (0.73-1.16)., Conclusions In-hospital complications after RC are numerous and continue to accumulate for many years after surgery, indicating the need for life-long follow-up of these patients., Comparison between different types of diversion should, however, be made with care because of potential confounding by indication. [ABSTRACT FROM AUTHOR]

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case–control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based. [ABSTRACT FROM AUTHOR]

Background. The aim of the present study was to compare both estrogen (ER) and progesterone receptor (PgR) content in operable breast cancers from Vietnamese and Swedish patients. Material and methods. Primary breast cancer tissues were randomly selected from 249 Vietnamese patients treated in Hanoi, Vietnam between 2002 and 2004 and 1 257 Swedish patients treated in Stockholm, Sweden between 2002 and 2003. Clinical information was available for all patients in the study. The hormone receptor content in tumors from Vietnam was analyzed by immunohistochemistry using an automated slide stainer (Bench MarkXT, Ventana) in combination with anti-ER (SP1 250), and anti-PgR (clone 1E2) rabbit monoclonal antibody. Tumors with ≥≥ 10% stained nuclei were considered as receptor positive. Tumors from Swedish patients were analyzed with an enzyme immunoassay with a cut-off point of ≥≥ 0.10 fmol/μμg DNA as positive. The hormone receptor frequencies between populations were compared according to clincopathology features. Results. The ER positive rate was higher in premenopausal and lower in postmenopausal Vietnamese patients as compared to Swedish patients with similar menopausal status (71% versus 58%, OR 1.75, p == 0.007; 44% versus 72%, OR 0.32, p < 0.001, respectively). PgR positive tumors were found in 58% and 25% of pre- and postmenopausal Vietnamese patients, respectively. The corresponding figures for Swedish patients were 73% and 66%, respectively. Conclusions. There were significant differences in the frequency of ER/PgR positivity between Vietnam and Swedish breast cancer patients. These differences were independent on menopausal status and age of patients at diagnosis can not be explained by these factors and they can be contributed to knowledge about both basic biology features and prognoses. [ABSTRACT FROM AUTHOR]

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]

Purpose: We assessed outcomes in terms of adverse pathology and prostate cancer specific mortality in men who underwent primary or deferred radical prostatectomy. Materials and Methods: In the National Prostate Cancer Register of Sweden Follow-Up Study men 70 years old or younger at diagnosis with localized low to intermediate risk prostate cancer diagnosed from 1997 to 2002 were identified. Outcome in terms of adverse pathology, namely upgrading of Gleason score, positive surgical margins and extraprostatic extension, as well as prostate cancer specific mortality, was assessed in 2,344 men who underwent primary radical prostatectomy and 222 who underwent deferred radical prostatectomy after an initial period of surveillance. Results: Upgrading of Gleason score in surgical specimens vs core biopsies was less frequent after primary (25%) vs deferred radical prostatectomy (38%), p <0.001. There was no significant difference in the percentage of men who underwent primary vs deferred radical prostatectomy for positive surgical margins (33% vs 24%) or extraprostatic extension (27% vs 25%), and there was no difference in any 1 or more of the 3 adverse pathology features (55% vs 56%). After a median followup of 8 years 0.7% of men in the primary radical prostatectomy group and 0.9% in the deferred radical prostatectomy group had died of prostate cancer. Conclusions: There was no significant difference in the presence of any 1 or more adverse pathology features or in prostate cancer specific mortality after primary compared to deferred radical prostatectomy. However, longer followup is needed to conclusively evaluate the role of deferred radical prostatectomy. [Copyright &y& Elsevier]

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]

Objective. To construct a database for clinical epidemiological prostate cancer research based on linkages between the National Prostate Cancer Register (NPCR) of Sweden, a population-based, nationwide quality database, and other nationwide registries. Material and methods. By use of the individually unique Swedish Personal Identity Number, the NPCR was linked to the Swedish Cancer Registry, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register and the Acute Myocardial Infarction Register, all held at the Centre for Epidemiology at the National Board of Health and Welfare, and the Register of the Total Population, the Longitudinal Integration Database for Health Insurance and Labor Market Studies and the Multi-Generation Register, held at Statistics Sweden, and to the Swedish Hernia Register. Results. Record linkages between the NPCR and the Swedish Cancer Registry, the Cause of Death Register and the Register of the Total Population generated a database, named PCBaSe Sweden, including 80 079 prostate cancer cases, diagnosed between 1 January 1996 and 31 December 2006. Record linkage between PCBaSe Sweden and the Prescribed Drug Register generated 59 721 unique matches and linkage to the Acute Myocardial Infarction Register resulted in 11 459 matches. Conclusion. PCBaSe Sweden is a newly created and unique database with over 80 000 cases of prostate cancer with comprehensive data on inpatient and outpatient care, patterns of use of prescribed drugs and socioeconomic and familial factors. Many topics in clinical prostate cancer epidemiology can be investigated. using PCBaSe Sweden. [ABSTRACT FROM AUTHOR]

Purpose: To what extent active surveillance and deferred treatment for localized risk prostate cancer are used is unclear. We assessed the use of surveillance and of deferred treatment in a population based, nationwide cohort in Sweden. Materials and Methods: In the National Prostate Cancer Register of Sweden, with a 98% coverage vs the compulsory Swedish Cancer Registry, we identified 8,304 incident cases of prostate cancer in 1997 to 2002 with age younger than 70 years, clinical local stage T1 or 2, N0 or Nx, M0 or Mx and serum prostate specific antigen less than 20 ng/ml. Data were extracted from medical charts for 7,782 of these men (94%) at a median of 4 years after diagnosis. Results: Primary treatment was surveillance for 2,065 men (26%), radical prostatectomy for 3,722 (48%), radiotherapy for 1,632 (21%) and hormonal treatment for 363 (5%). Men on surveillance had lower local tumor stage, grade and prostate specific antigen, and were older than those who received active primary treatment (p <0.001). After a median surveillance of 4 years 711 men (34%) on surveillance had received deferred treatment, which was radical prostatectomy for 279 (39%), radiotherapy for 212 (30%) and hormonal treatment for 220 (30%). Conclusions: Surveillance was a common treatment for patients younger than 70 years with localized prostate cancer in Sweden in 1997 to 2002, 26% of men with localized prostate cancer started surveillance and after a median followup of 4 years, 66% of these men remained on surveillance. [Copyright &y& Elsevier]

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]

Objective. Widowhood imposes difficult psychological, social and practical challenges. We investigated the prevalence and predictors of access to bereavement interventions during the first 6 months after the loss of a husband/male partner to prostate or urinary bladder cancer. Material and methods. All women (n = 506) aged <80 years living in Sweden who lost their husband/partner owing to cancer of the prostate in 1996 or of the urinary bladder in 1995 or 1996 were asked to answer an anonymous postal questionnaire 2-4 years after their loss. Results. Thirty percent of the widows stated that they would not have needed psychological support by caregivers during the first 6 months of bereavement. Two-thirds of the others (162/242) (those who did not state that they had no need of support) did not have any access to psychological support, 10% (25/242) had little access, 11% (27/242) had moderate access and 12% (28/242) had a large amount of access to psychological support. Similar figures were observed for other bereavement interventions, such as information, economic counselling and support groups. Emotional relations during the last months prior to bereavement, intensity of faith, education, prior mental health problems and a diagnosis of prostate cancer were all positively correlated with access to psychological support by caregivers, whereas previously identified risk factors for excess morbidity in widowhood were not. Conclusions. A large majority of Swedish widows who lost their husband to urologic cancers in 1995 or 1996 indicated a need for psychological support, information and economic counselling. This need was not met by caregivers and help was not aimed at important groups at risk of morbidity. [ABSTRACT FROM AUTHOR]

Objectives. To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. Material and methods. Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35 223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. Results. Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged <70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA >100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8–10) had a markedly reduced relative 5-year survival rate. Conclusions. It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation. [ABSTRACT FROM AUTHOR]

Objective: To investigate to what extent prostate cancer patients confide their emotional concerns, and whether having no one to confide in affects well-being. Material and methods: A population-based study using epidemiological methods. A questionnaire was mailed to all 431 living prostate cancer patients aged 50-80 at the time of selection, diagnosed 1.5-2 years previously in Stockholm County, and 435 randomly selected men in the same age group. The questionnaire was completed anonymously. The main outcome measures included questions assessing the extent to which the men could share emotionally taxing feelings with their partner or others and questions assessing well-being. Results: The questionnaire was returned by 79% of the patients and by 73% of the randomly selected men. Approximately one in five patients had no one to confide in. Of patients living with a partner, only one in 10 confided in someone other than their partner. Three out of 10 patients living in a relationship could not confide in their partner. Men having no one to confide in were less content with their life and reported poorer psychological and overall well-being compared with other men. The prostate cancer patients were not more likely to have someone to confide in than men in general. Conclusions: The results indicate that a lack of emotional support may be a problem for many prostate cancer patients and that the traditional psychosocial support offered to most cancer patients in Sweden may not reach male patients. There may be a need for a gender-adapted approach to emotional support. [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.

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]

Abstract – Objective: To assess tobacco prevention in Swedish dental care and to identify barriers. Also, to investigate whether dentists and dental hygienists were familiar with recently published review of smoking cessation methods. Methods: A questionnaire was mailed to all 353 dental hygienists and 528 dentists in Stockholm County. Results: The overall response rate was 61% for the dentists and 67% for the dental hygienists. Nearly all considered smoking to be a major health issue, but one out of two was not convinced that smokeless tobacco use was a major health problem. A small minority was routinely engaged in cessation support. However, on the aggregate level, the active dentists and hygienists advised annually approximately 70 000 and 40 000 smokers, respectively. The main barrier to cessation counseling was lack of smoking cessation experts to refer to and was followed by a lack of reimbursement, a lack of knowledge, time constraints, and a feeling of inadequacy. Also, one out of two dentists and 3 out of 10 hygienists did not see it as a part of their job to help patients stop smoking. Approximately 10% in both groups made use of the review of smoking cessation methods. Fifty per cent of these had increased their cessation consultations by an average of 30% because of the guidelines. On the average, dentists and hygienists had spent approximately 1.4 and 2.9 h, respectively, during the previous month on all smoking cessation activities. Conclusions: Despite several barriers, there is an excellent potential for a more active role in tobacco cessation counseling in Swedish dental care. [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]

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]

Background Symptoms of terminal cancer have previously been reported as undertreated. The aim of this study was to assess the use of palliative medications before death from prostate cancer. Methods This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer. Results We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47–0.66 for >85 years versus <70 years) and (OR 0.78, 95% CI: 0.66–0.92 for unmarried without children versus married with children). Conclusion Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer. [ABSTRACT FROM AUTHOR]

Background A decreased risk of prostate cancer (PCa) has been suggested in men taking aspirin, statins and metformin, although the evidence has been conflicting. We estimated the association between prescribed medications, prostate specific antigen (PSA) levels and the risk of either any PCa or high-grade PCa. Methods This population-based cohort study included 185,667 men having a first recorded PSA test and 18,574 men having a first prostate biopsy in Stockholm County, Sweden for the period 2007–2012. Detailed clinical information including PSA levels, biopsy results, comorbidities and educational level were obtained from population-based registers. High-grade prostate cancer was defined as a Gleason score of seven or higher. Differences in PSA levels by medication status were estimated using linear regression on log PSA values. PCa risk was estimated using multivariate logistic regression. Results Compared with men who were not on medication, the PSA level at the first PSA test was lower among men using 75 mg/dose aspirin (−3.9% change in PSA concentration; 95% confidence interval (CI): −5.8 to −2.1), statin (−4.6%; 95% CI: −6.2 to −2.9), metformin (−14%; 95% CI: −17 to −12) and insulin (−16%; 95% CI: −18 to −14). Men using any statins had an increased risk of both high-grade PCa (odds ratio (OR) 1.25; 95% CI: 1.10–1.42) and PCa of any grade (OR 1.16; 95% CI 1.04–1.29). There were no significant associations between aspirin or any antidiabetic medication and the risk of PCa. Conclusion We found no protective effect of aspirin, statins or antidiabetics in terms of risk for any PCa or high-grade PCa. Use of any statins was associated with an elevated risk of being diagnosed with high-grade prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Register-based studies have shown large survival differences among prostate cancer patients in the Nordic countries. The aim of this study was to determine the background of such differences in Denmark, Iceland and Sweden. Material and methods: Patients with prostate cancer were identified through population-based cancer registers in the three countries. Clinical findings at diagnosis were retrieved from hospital records. In Sweden, clinical information was gathered from regional population-based prostate cancer registers. Country-specific incidence and excess mortality rates were compared, with adjustment for prognostic factors. Results: The relative survival in the cohorts was comparable to that in previous population-based studies. Significant differences in excess mortality rates were found across countries, which diminished or disappeared after adjustment for patient characteristics, i.e. metastatic status, clinical T stage and prostate-specific antigen level. A difference in the proportion of patients with metastatic disease was the main explanation of the differences in survival among countries, while the incidence rates of metastatic cancer were similar. Discussion: Register-based studies of the relative survival of prostate cancer patients are influenced by national differences in clinical presentation at diagnosis. Differences in the proportion of patients with metastatic spread explained most of the difference in relative survival among patients in Denmark, Iceland and Sweden. Future country comparisons of relative survival should include adjustment for differences in patient characteristics, such as stage, prostate-specific antigen level and screening intensity. [Copyright &y& Elsevier]

Abstract: Purpose: Risk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing. Patients and Methods: Relative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997–2009 to 528,658 matched prostate cancer-free men. Results: During the first 6months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0–10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000PY, RR 10 (95% CI 5.1–21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000PY and RR 5.2 (95% CI 2.3–12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000PY, RR 1.0 (95% CI 0.68–1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000PY, RR 1.8 (95% CI 1.1–2.9). Conclusion: Although the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness. [Copyright &y& Elsevier]

Abstract: Background: Prostate-specific antigen (PSA) testing has increased in several countries. There is incomplete knowledge of PSA testing patterns. Objective: Determine the prevalence of PSA testing and explore patterns of PSA retesting in Stockholm County, Sweden. Design, setting, and participants: A population-based study was performed. Through registry linkages, we collected population information, data on PSA tests, pathology reports, and clinical information. The study population comprised males living in Stockholm County in 2011 (n =1034129), of which 229 872 had a PSA test during the period 2003–2011. Outcome measurements and statistical analysis: We determined limited-duration-point prevalence of PSA testing and performed survival analysis on PSA retesting for men aged 40–89 yr. Results and limitations: The number of PSA tests increased from 54239 in 2003 to 124613 in 2011. During the 9-yr study period, 46%, 68%, and 77% of men without a prior prostate cancer (PCa) diagnosis and aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. During 2010 and 2011, 25%, 40%, and 46% of men aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. The prevalence of PSA testing increased from 2003 to 2011. The probability of retesting was PSA and age dependent, with a 26-mo cumulative incidence of 0.337 (95% confidence interval, 0.333–0.341) if the first PSA value was <1 ng/ml. The main limitations were (1) that PSA data prior to 2003 were not available and (2) that the study cohort was restricted to men who were alive in 2011. Conclusions: Although screening for PCa is not recommended in Sweden, PSA testing in Stockholm County was high across ages ranging from 40 to 89 yr and increased during the period 2003–2011. The probability of PSA retesting was high, regardless of the original PSA level. These results contrast with current clinical recommendations and raise calls for a change, either through structured PCa testing or more detailed guidelines on PSA testing. [Copyright &y& Elsevier]

Abstract: Background: Prostate cancer patients have an increased risk of fractures as a consequence of skeletal metastases and osteoporosis induced by endocrine treatment. Data on incidence of fractures and risks in subgroups of men with prostate cancer are sparse. Our aim with this study is to report the risk of fractures among men with prostate cancer in a nationwide population-based study. Patients and methods: We identified 76,600 Swedish men diagnosed with prostate cancer 1997–2006 in the Prostate Cancer Data Base (PCBaSe) Sweden and compared the occurrence of fractures requiring hospitalisation with the Swedish male population. Results: Only men treated with gonadotropin releasing-hormone (GnRH) agonists or orchiectomy had increased incidence and increased relative risk of fractures requiring hospitalisation. Men treated with GnRH agonists had 9.8 and 6.3/1000 person-years higher incidence of any fracture and hip fracture requiring hospitalisation than the general population. The corresponding increases in incidence for men treated with orchiectomy were 16 and 12/1000 person-years, respectively. Men treated with orchiectomy, GnRH agonists, and antiandrogen monotherapy, had SIR for hip fracture of 2.0 (95% Confidence Interval 1.8–2.2), 1.6 (95% CI 1.5–1.8) and 0.9 (95% CI 0.7–1.1), respectively. Men treated with a curative intent (radical prostatectomy or radiotherapy) or managed with surveillance had no increased risk of fractures. Older men had the highest incidence of fractures while younger men had the highest relative risk. Conclusion: Prostate cancer patients treated with GnRH agonists or orchiectomy have significantly increased risk of fractures requiring hospitalisation while patients treated with antiandrogen monotherapy had no increase in such fractures. In absolute terms the excess risk in men treated with GnRH agonists corresponded to almost 10 extra fractures leading to hospitalisation per 1000 patient-years. Effects on bone density should be considered for men on long-term endocrine treatment. Unwarranted use of orchiectomy and GnRH agonists should be avoided. [Copyright &y& Elsevier]

Abstract: Background: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events. Objective: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis. Design, setting, and participants: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden. Measurements: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events. Results and limitations: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28–1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated. Conclusions: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis. [Copyright &y& Elsevier]

Abstract: Background: Outcomes for many cancer forms are associated with socioeconomic status (SES).We investigated if SES was associated with management and mortality in men with high risk prostate cancer. Material and methods: A nation-wide population-based cohort in Prostate Cancer Data Base Sweden (PCBaSe), a merged database including data on incident prostate cancer identified in the National Prostate Cancer Register (NPCR) between 1997 and 2006. High risk PCa was defined as T3 tumour, and/or Gleason score 8–10 and/or PSA 20–50ng/mL. Use of bone scan, curative treatment, and mortality in relation to SES was assessed by logistic, Cox, and competing risk regression with hazard ratios (HR), sub-distributed HR and 95% confidence intervals (CI) adjusted for co-morbidity, age, calendar period and clinical subgroups. Results: Amongst 17,522 high risk prostate cancer patients, a bone scan was more often performed in higher white-collar than in blue-collar workers (OR 1.30; 95% CI 1.21–1.40). Amongst men without metastases, the likelihood of intention to treat was higher in higher white-collar workers (OR 1.43; 95% CI 1.28–1.57). In men who received curative treatment, the likelihood was higher to undergo radical prostatectomy for higher white-collar patients (OR 1.29; 95% CI 1.10–1.47). In men without metastases, not only overall mortality was lower amongst higher white-collar workers (HR, 0.76; 95% CI 0.60–0.97), but also prostate cancer-specific mortality (sHR 0.70; 95% CI, 0.49–0.99). Conclusions: We conclude that socioeconomic disparities in the management and mortality in men with high risk prostate cancer exist also within the setting of a National Health Care System aiming to provide care on equal terms to all residents. [Copyright &y& Elsevier]

Abstract: Aim: To explore whether the self-reported psychological distress among men with prostate cancer was to the extent that it required psychiatric treatment. Methods: PCBaSe Sweden, a merged database based on the National Prostate Cancer Register including 97% of all prostate cancers registered as well as age-matched controls. We calculated relative risks and 95% confidence intervals to compare risks of psychiatric treatment due to depression, anxiety, and post-traumatic stress disorder controlling for age and socio-economic factors. We used odds ratios to compare use or no use of antidepressants. Findings: In total 72,613 men with prostate cancer and 217,839 men without prostate cancer were included for analyses. Psychiatric hospitalisation due to depression, anxiety and post-traumatic stress disorder were significantly increased (RR 1.29, (95% CI 1.14–1.45), RR 1.42 (95% CI 1.12–1.80) and RR 1.61 (95% CI 1.16–2.24), respectively). However, hospitalisations due to anxiety were only increased in men with more advanced tumours RR 2.28 (95% CI 1.45–3.57). The use of antidepressants was increased for all men with prostate cancer RR 1.65 (95% CI 1.54–1.77) and treatment strategies RR 1.93 (95% CI 1.75–2.13). Interpretation: Men diagnosed with prostate cancer had increased risk of psychiatric treatment for depression, post-traumatic stress disorder and use of antidepressants regardless of risk group and treatment strategy compared to age-matched controls, whilst more advanced prostate cancer was associated with severe anxiety disorders. [Copyright &y& Elsevier]

Abstract: Purpose: To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30years. Material and methods: 72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976–2006 and followed prospectively. Radiation-related risk was studied by comparing women with left-sided and right-sided tumours. Results: 34,825 women (48%) received radiotherapy. Among unirradiated women tumour laterality had little relevance to heart disease. Among irradiated women mean dose to the whole heart was 6.3Gy for left-sided tumours and 2.7Gy for right-sided tumours. Mortality was similar in irradiated women with left-sided and right-sided tumours, but incidence ratios, left-sided versus right-sided, were raised: acute myocardial infarction 1.22 (95% CI 1.06–1.42), angina 1.25 (1.05–1.49), pericarditis 1.61 (1.06–2.43), valvular heart disease 1.54 (1.11–2.13). Incidence ratios for all heart disease were as high for women irradiated since 1990 (1.09 [1.00–1.19]) as for women irradiated during 1976–1989 (1.08 [0.99–1.17]), and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women (1.58 [1.19–2.10] versus 1.08 [1.01–1.15], p for difference=0.01). Conclusions: Breast cancer radiotherapy has, at least until recently, increased the risk of developing ischaemic heart disease, pericarditis and valvular disease. Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others. [Copyright &y& Elsevier]

Abstract: Our purpose was to investigate whether alcohol (ethanol) consumption could have an influence on the metabolism of acrylamide to glycidamide in humans exposed to acrylamide through food. We studied a subsample from a population-based case–control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol intake estimates was compared to the ratio of hemoglobin-adduct levels for acrylamide and glycidamide, used as a measure of individual differences in metabolism. Data from 161 non-smoking men were processed with regard to the influence of alcohol on the metabolism of acrylamide to glycidamide. A negative, linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with increasing alcohol intake was observed and the strongest association (p-value for trend=0.02) was obtained in the group of men with the lowest adduct levels (⩽47pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels. The observed trend is likely due to a competitive effect between ethanol and acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly indicating that ethanol influence metabolism of acrylamide to glycidamide, partly explain earlier observations of only low to moderate associations between questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels. [Copyright &y& Elsevier]

Abstract: Background: The risk of suicide is increased among cancer patients including men with prostate cancer (PCa). However, whether this increased risk applies to men diagnosed subsequent to prostate-specific antigen (PSA) testing is not known. Objective: To assess the risk of suicide among men diagnosed with PCa subsequent to PSA testing. Design, setting, and participants: The Prostate Cancer Base Sweden (PCBaSe Sweden) database, the Swedish Cause of Death Register, and the Swedish census database were used. The PCBaSe Sweden is a merged database that includes data from the Swedish National Prostate Cancer Register (NPCR) for cases diagnosed between January 1, 1997, and December 31, 2006. The number of suicides registered for cases in the PCBaSe cohort was compared with the expected number of suicides in an age-matched general male Swedish population. Measurements: Standardised mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated for different categories of cases. Results and limitations: There were 128 suicides among the 77 439 PCa cases in the NPCR compared with an expected number of 85 (SMR: 1.5; 95% CI, 1.3–1.8). The risk of suicide was not increased for the 22 405 men with PSA-detected T1c tumours (SMR: 1.0; 95% CI, 0.6–1.5), whereas the 22 929 men with locally advanced nonmetastatic tumours (SMR: 2.2; 95% CI, 1.6–2.9) and the 8350 men with distant metastases (SMR: 2.1; 95% CI, 1.2–3.6) had statistically significant increased SMRs for suicide. Potential effects of comorbid medical and psychiatric conditions could not be investigated. Conclusions: No increased risk of committing suicide was observed among men with PCa diagnosed subsequent to PSA testing, whereas the risk was twice as high among men with locally advanced or metastatic disease, compared with an age-matched male population. [Copyright &y& Elsevier]

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., (© 2022. The Author(s).)

Background: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM., Methods: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association., Results: There were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80), when we defined the worsening control of diabetes by combining all definitions above., Conclusion: Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH., (© 2021. The Author(s).)

Background: Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties., Methods: A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides., Results: Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings., Conclusion: PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.

Importance: Diabetic men appear to have a lower risk of prostate cancer. Whether antidiabetic medications are protective or potentially mask prostate cancer by lowering prostate-specific antigen (PSA) levels is unclear., Objective: To examine the associations of antidiabetic medication use with (1) PSA levels, (2) frequency of PSA testing, (3) receipt of biopsy following elevated PSA results, and (4) prostate cancer detection at biopsy., Design, Setting, and Participants: Population-based cohort study using data from the Stockholm PSA and Biopsy Register. Participants were all prostate cancer-free men aged 40 to 79 years residing in Stockholm County, Sweden, between January 1, 2006, and December 31, 2015. Data were analyzed from November 2018 to March 2019., Exposures: One or more prescription for metformin, sulfonylurea, or insulin, as recorded in Sweden's National Prescribed Drug Register., Main Outcomes and Measures: Levels of PSA following first exposure to antidiabetic medications were assessed using multivariable linear regression. Frequency of PSA testing was assessed via multivariable Poisson regression. Biopsy following elevated PSA (≥3.0 ng/mL) and prostate cancer detection at biopsy were assessed via multivariable logistic regression., Results: The cohort of 564 666 men (median [range] age, 65 [40-79] years) consisted of 4583 men initially exposed to metformin, 1104 exposed to sulfonylurea, and 978 exposed to insulin who were age matched with unexposed men (1:5). Exposed men had lower median (interquartile range) PSA levels before starting antidiabetic medications compared with unexposed men (1.2 [0.7-2.5] vs 1.6 [0.8-3.2] ng/mL). After accounting for baseline differences, PSA levels did not vary from those of unexposed men following exposure to antidiabetic medications. Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81). Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93). There were no differences in prostate cancer detection at biopsy, regardless of PSA levels that triggered the biopsy., Conclusions and Relevance: This study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer. They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes.

Background: Although prostate-specific antigen (PSA) testing is common, little is known about the pattern of retesting by either PSA values or subsequent prostate biopsies. Poor follow-up of high PSA values may lead to delayed diagnosis., Objective: To estimate the probabilities of follow-up (including retesting, prostate biopsies, diagnosis, and cause-specific death) for men undergoing prostate cancer testing at a population level., Design, Setting, and Participants: Cohort study design for men living in Stockholm with no previous diagnosis of prostate cancer between 2003 and 2015. Men were linked to the national health and population registries in Sweden. We report follow-up for men aged 50-79 yr at 2003 or at their index PSA test., Outcome Measurements and Statistical Analysis: State probabilities with 95% confidence intervals (CIs) were calculated using multistate Markov models., Results and Limitations: Among men not previously diagnosed with prostate cancer with an initial PSA value of ≥10ng/ml, the proportions at 1 yr with no subsequent testing or only elevated PSA test values >3ng/ml were 21.7% (95% CI: 19.5, 23.9), 25.2% (95% CI: 23.9, 26.6), and 47.7% (95% CI: 46.2, 49.1) for those aged 50-59, 60-69, and 70-79 yr, respectively. No significant changes were noticed when stratifying by comorbidities. Limitations include the lack of detail from patient medical charts. This detail would have allowed for more accurate assessment of appropriate clinical follow-up., Conclusions: Regardless of medical history, a large proportion of men with PSA≥10ng/ml were not followed appropriately at 1 yr after the index PSA test. This may partially explain why opportunistic testing is not as effective as screening within trials to reduce prostate cancer mortality., Patient Summary: For men aged 50-69 yr, who undertake a prostate-specific antigen (PSA) test, a PSA level of >10ng/ml should prompt further investigation. However, we found that one out of 10 of these men did not receive repeat testing within 1 yr of the initial test. This may partially explain why opportunistic prostate cancer testing is less effective than screening trials., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia., Methods: Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer-free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non-Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW., Results: A total of 25 967 men with prostate cancer and 121 018 prostate cancer-free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin-releasing hormone agonist treatment ( HR 1.15, 95% confidence interval [CI] 1.07-1.23) and orchiectomy (HR 1.60, 95% CI 1.32-1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer-free men; however, this increase in risk was only observed for non-Alzheimer's dementia and occurred from year 1-4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW., Conclusion: This population-based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non-Alzheimer's dementia., (© 2019 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk., Methods: Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007-2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose., Results: Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04-1.12) but not 'unfavourable' (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma > 5 years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05-1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24-1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p < 0.011)., Conclusion: Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.

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 5yr before through to 5yr 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., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: More specific diagnostic for prostate cancer is needed to decrease overdetection and number of diagnostic procedures., Objective: To assess the performance of combining a blood-based biomarker panel and magnetic resonance imaging (MRI)-targeted biopsies for prostate cancer detection., Design, Setting, and Participants: We used a prospective, multicenter, paired diagnostic study design. A total of 532 men aged 45-74 yr referred for prostate cancer workup were included during 2016-2017., Intervention: Participants underwent blood sampling for analysis of the Stockholm3 test including protein biomarkers, genetic polymorphisms, and clinical variables; 1.5 T MRI; systematic prostate biopsies; and MRI-targeted biopsies to lesions with Prostate Imaging Reporting and Data System version 2 ≥3., Outcome Measurements and Statistical Analysis: The main outcome was numbers of detected prostate cancer characterized by grade group (GG) and the number of performed biopsies using relative sensitivity (RS)., Results and Limitations: Median prostate-specific antigen was 6.3 ng/ml, and mean age was 63.9 yr. Targeted and systematic biopsies detected 170 and 162 GG ≥2 tumors, respectively (RS 1.05; 95% confidence interval [CI] 0.96-1.14). Compared with performing systematic biopsies on all men, performing targeted and systematic biopsies only on men with >10% risk of GG ≥2 cancer, as predicted by the Stockholm3 test, required 62% (95% CI 58-66) of the biopsy procedures and detected 58% (95% CI 48-70) of GG 1 disease, with increased sensitivity for GG ≥2 detection (RS 1.10; 95% CI 1.02-1.17). Performing only targeted biopsies in men with elevated Stockholm3 test altered these results only slightly. Compared with performing systematic and targeted biopsies on all men, performing this only for men with an elevated Stockholm3 test decreased detection of GG ≥2 cancer slightly (RS 0.92; 95% CI 0.88-0.95). Limitations include lacking knowledge of true disease prevalence., Conclusions: These findings provide evidence that strategies combining the blood-based Stockholm3 test and MRI-targeted biopsies can be used to inform biopsy decision making., Patient Summary: In this study, 532 men coming for prostate cancer workup underwent blood sampling, and both traditional and magnetic resonance imaging/fusion-guided prostate biopsies. We report that performing targeted biopsies only in men with an elevated risk as assessed by the Stockholm3 test saved biopsies, decreased overdetection, and maintained the number of detected high-grade cancers., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: In 2007, the Swedish National Board of Health and Welfare published the first Swedish guidelines on prostate cancer (PCa) to improve care and decrease geographical and social inequalities. The aim of this analysis was to assess how these guidelines affected PCa care., Materials and Methods: Work-up and treatment for men diagnosed with PCa between 1998 and 2014 were assessed by use of data in the Prostate Cancer data Base Sweden (PCBaSe) with information from the National Prostate Cancer Register (NPCR) and other healthcare registries and demographic databases., Results: Overall, there were modest improvements in the performance for 14 selected quality indicators, with some notable exceptions. There was a strong increase in the use of active surveillance for very low-risk PCa, up from 56% in 2009 to 92% in 2014, and use of bone imaging for high-risk PCa up from 50% in 2008 to 77% in 2014. There were large differences in work-up and treatment of PCa between healthcare providers with modest decreases over time. The differences between counties were larger than differences according to socioeconomic status with one exception: use of curative treatment for high-risk PCa was more common in men with high income, highest versus lowest tertile, OR 2.74 (95% CI, 1.85-4.06)., Conclusion: The modest improvements in PCa care after the publications of national guidelines indicate that if these are to make an impact on care, feedback to each point of care on their performance as well as local quality improvement programs implementing the guidelines are needed.

Background: There are no conclusive results from randomized trials on radiotherapy (RT) versus radical prostatectomy (RP) for prostate cancer. Numerous observational studies have suggested that RP is associated with a lower risk of prostate cancer death, but whether results have been biased due to limited adjustments for confounding factors is unknown., Objective: To compare the risk of prostate cancer death after RT versus RP., Design, Setting, and Participants: Nationwide population-based observational study of men in the Prostate Cancer data Base Sweden 3.0 who had undergone RT or RP between 1998 and 2012., Outcome Measurements and Statistical Analysis: Prostate cancer deaths were compared. Hazard ratios (HRs) were calculated in Cox regression models, including clinical T stage, M stage, Gleason grade group, serum levels of prostate-specific antigen, proportion of biopsy cores with cancer, mode of detection, comorbidity, age, educational level, and civil status. Period analysis with left truncation was performed., Results and Limitations: Primary treatment was RT or RP for 41 503 men. Treatment effect was associated with disease severity. In univariate analysis of RT versus RP, risk of prostate cancer death was higher after RT-low- and intermediate-risk cancer, HR 1.82 (95% confidence interval [CI]: 1.53-2.16), and high-risk cancer, HR 1.57 (95% CI: 1.33-1.85). After full adjustment in period analysis, this difference between the treatments was attenuated-low- and intermediate-risk cancer, HR 1.24 (95% CI: 0.97-1.58), and high-risk cancer, HR 1.03 (95% CI: 0.81-1.31). Confounding remained due to nonrandom allocation to treatment., Conclusions: In comparison with previous studies, the difference in prostate cancer mortality after RT and RP was much smaller., Patient Summary: The difference in prostate cancer mortality after contemporary radiotherapy and radical prostatectomy was small in contrast to previous studies, indicating that potential side effects should be more emphasized when selecting treatment., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)