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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]

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: In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories. Material and Methods: We emulated a trial using data from Prostate Cancer data Base Sweden 3.0. We specifically focused on men diagnosed in 2006-2012 with high-risk PCa who had no distant metastasis. They either received primary hormonal therapy with AA (n¼2078) or GnRH agonists (n¼4878) who were followed for a median time of 5 years. Risk of death from PCa and other causes was assessed using competing risk analyses and Cox proportional hazards regression analyses, including propensity score matching. Results: The cumulative 5-year PCa mortality was lower for men treated with AA (16% [95% confidence interval, CI, 15-18%]) than men treated with GnRH agonists (22% [95% CI 21-24%]). The 5-year other cause mortality was also lower for men on AA (17% [95% CI 15-19%] compared to men on GnRH agonists (27% [95% CI 25-28%]). In regression analyses, the risk of PCa death was similar, GnRH agonists versus AA (reference), hazard ratio (HR) 1.08 (95% CI 0.95-1.23), but the risk of death from all causes was higher for men on GnRH agonists, HR 1.23 (95% CI 1.13-1.34). Consistent results were seen in the propensity score-matched cohort. Conclusion: Our results indicate that the use of AA as primary hormonal therapy in men with highrisk non-metastatic PCa does not increase PCa-specific mortality compared to GnRH. Using AA instead of GnRH agonists may result in shorter time on/exposure to GnRH-treatment, which may reduce the risk of adverse events associated with this treatment. [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]

As epidemiological methods are used increasingly to evaluate the effects of cancer treatment, guidelines for the application of such methods in clinical research settings are necessary. Towards this end, we present a hierarchical step-model for causation of bias, which depicts a real-life study as departing from a perfect setting and proceeding step-wise towards a calculated, often adjusted, effect-parameter. Within this model, a specific error (which influences the effect-measure according to one of four sets of rules) is introduced on one (and only one) of the model's four steps. This hierarchical step-model for causation of bias identifies all sources of bias in a study, each of which depicts one or several errors which can be further categorized into one of the model's four steps. Acceptance of this model has implications for ascertaining the degree to which a study effectively evaluates the effects of cancer treatment (level of scientific evidence). [ABSTRACT FROM AUTHOR]

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.

Objective: The aim of this study was to determine whether educational length affects prostate-specific antigen (PSA) testing and the time to prostate biopsy for men with raised PSA values., Materials and Methods: Using register data on all men in Stockholm County in 2013 (n = 1,052,841), the limited-duration point prevalence of PSA testing and time between test and prostate biopsy or repeat testing were analysed. Patterns of follow-up were assessed using Kaplan-Meier product limit estimators and Cox proportional hazard models. Educational length was categorized as short (≤ 9 years), intermediate (10-12 years) or long (≥ 13 years)., Results: PSA testing increased with educational length in all age groups. Among men aged 50-69 years, 61% with long and 54% with short education had had a PSA test within the preceding 10 years (p < 0.001). In men with PSA 4-10 ng/ml, 40% [95% confidence interval (CI) 38-41] with long and 27% (95% CI 26-29) with short education underwent a prostate biopsy within 12 months. After adjusting for PSA level and age, educational length was still associated with the chance of having a prostate biopsy in men with PSA 4-10 ng/ml (hazard ratio 1.22, 95% CI 1.12-1.31), but not in men with higher PSA values., Conclusion: PSA testing increased with educational length. Men with long education were more likely to have a prostate biopsy after an increased PSA value below 10 ng/ml than men with short education. These differences may contribute to the worse prostate cancer outcomes observed among men with lower socioeconomic status.