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OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

Background: Studies identifying risk factors for death from breast cancer after ductal carcinoma in situ (DCIS) are rare. In this retrospective nested case-control study, clinicopathological factors in women treated for DCIS and who died from breast cancer were compared with those of patients with DCIS who were free from metastatic disease. Methods: The study included patients registered with DCIS without invasive carcinoma in Sweden between 1992 and 2012. This cohort was linked to the National Cause of Death Registry. Of 6964 women with DCIS, 96 were registered with breast cancer as cause of death (cases). For each case, up to four controls (318; women with DCIS, alive and without metastatic breast cancer at the time of death of the corresponding case) were selected randomly by incidence density sampling. Whole slides of tumour tissue were evaluated for DCIS grade, comedo necrosis, and intensity of periductal lymphocytic infiltrate. Composition of the immune cell infiltrate, expression of oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki-67 were scored on tissue microarrays. Clinical information was obtained from medical records. Information on date, site, and histological characteristics of local and distant recurrences was obtained from medical records for both cases and controls. Results: Tumour tissue was analysed from 65 cases and 195 controls. Intense periductal lymphocytic infiltrate around DCIS was associated with an increased risk of later dying from breast cancer (OR 2.21. 95% c.i. 1.01 to 4.84). Tumours with more intense lymphocytic infiltrate had a lower T cell/B cell ratio. None of the other biomarkers correlated with increased risk of breast cancer death. Conclusion: The immune response to DCIS may influence the risk of dying from breast cancer.

Importance: It is uncertain to what extent watchful waiting (WW) in men with nonmetastatic prostate cancer (PCa) and a life expectancy of less than 10 years is associated with adverse consequences. Objective: To report transitions to androgen deprivation therapy (ADT), castration-resistant prostate cancer (CRPC), death from PCa, or death from other causes in men treated with a WW strategy. Design, Setting, and Participants: This nationwide, population-based cohort study included men with nonmetastatic PCa diagnosed since 2007 and registered in the National Prostate Cancer Register of Sweden with WW as the primary treatment strategy and with life expectancy less than 10 years. Life expectancy was calculated based on age, the Charlson Comorbidity Index (CCI), and a drug comorbidity index. Observed state transition models complemented observed data to extend follow-up to more than 20 years. Analyses were performed between 2022 and 2023. Exposure: Nonmetastatic PCa. Main Outcomes and Measures: Transitions to ADT, CRPC, death from PCa, and death from other causes were measured using state transition modeling. Results: The sample included 5234 men (median [IQR] age at diagnosis, 81 [79-84] years). After 5 years, 954 men with low-risk PCa (66.2%) and 740 with high-risk PCa (36.1%) were still alive and not receiving ADT. At 10 years, the corresponding proportions were 25.5% (n = 367) and 10.4% (n = 213), respectively. After 10 years, 59 men with low-risk PCa (4.1%) and 221 with high-risk PCa (10.8%) had transitioned to CRPC. Ten years after diagnosis, 1330 deaths in the low-risk group (92.3%) and 1724 in the high-risk group (84.1%) were from causes other than PCa. Conclusions and Relevance: These findings suggest that the WW management strategy is appropriate for minimizing adverse consequences of PCa in men with a baseline life expectancy of less than 10 years.

Objectives: To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP). Material and Methods: Men diagnosed with HRLPC in 2006–2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow-up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event. Results: In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow-up was 6.2 (3.6–9.5) years. After RT, the 10-year risk of PCa-related death was 0.13 (95% confidence interval [CI] 0.12–0.14) and the risk of death from all causes was 0.32 (95% CI 0.31–0.34). After RP, the 10-year risk of PCa-related death was 0.09 (95% CI 0.08–0.10) and the risk of death from all causes was 0.19 (95% CI 0.18–0.21). The 10-year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41–0.44) and 0.21 (95% CI 0.20–0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa-related death at 10 years after initiation of ADT was 0.33 (95% CI 030–0.36) after RT and 0.27 (95% CI 0.24–0.30) after RP. Conclusion: Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted.

Background and objectives: Changes in work-up and histopathological assessment have caused stage and grade migration in men with prostate cancer (PCa). The aim of this study was to assess temporal trends in risk of PCa death for men with favourable-risk PCa managed with primary radical prostatectomy or observation. Methods and material: Men aged 75 or younger with Charlson Comorbidity index 0–1 diagnosed with favourable-risk PCa (T1–T2, prostate specific antigen [PSA] <20 ng/mL and Gleason score 6 or 7[3+4]) in the period 2000–2016 who were treated with primary radical prostatectomy or managed with observation in PCBaSe 4.0. Treatment groups were compared following propensity score matching, and risk of PCa death was estimated by use of Cox regression analyses. Results: A total of 9,666 men were selected for each treatment strategy. The 7-year cumulative incidence of PCa death decreased in all risk and treatment groups. For example, the incidence in men diagnosed with low-risk PCa and managed with observation was 1.2% in 2000–2005, which decreased to 0.4% in 2011–2016. Corresponding incidences for men with intermediate-risk PCa managed with observation were 2.0% and 0.7%. The relative risk of PCa death was lower in men with low-risk PCa managed with radical prostatectomy compared to observation: in 2000–2005 hazard ratio (HR) 0.20 (95% confidence interval [CI] 0.10–0.38) and in 2011–2016 HR 0.35 (95% CI 0.05–2.26). Corresponding risks for men with intermediate-risk PCa were HR 0.28 (95% CI 0.16–0.47) and HR 0.21 (95% CI 0.04–1.18). The absolute risk reduction of radical prostatectomy compared to observation for men with low-risk PCa was 1% in 2000–2005 and 0.4% in 2011–2016, and for men with intermediate-risk PCa 1.1% in 2000–2005 and 0.7% in 2011–2016. Conclusion: Men diagnosed in 2011–2016 with low-risk and favourable intermediate-risk PCa have a similar relative benefit but smaller absolute benefit of curative treatment compared to m, BACKGROUND AND OBJECTIVES: Changes in work-up and histopathological assessment have caused stage and grade migration in men with prostate cancer (PCa). The aim of this study was to assess temporal trends in risk of PCa death for men with favourable-risk PCa managed with primary radical prostatectomy or observation. METHODS AND MATERIAL: Men aged 75 or younger with Charlson Comorbidity index 0-1 diagnosed with favourable-risk PCa (T1-T2, prostate specific antigen [PSA] <20 ng/mL and Gleason score 6 or 7[3+4]) in the period 2000-2016 who were treated with primary radical prostatectomy or managed with observation in PCBaSe 4.0. Treatment groups were compared following propensity score matching, and risk of PCa death was estimated by use of Cox regression analyses. RESULTS: A total of 9,666 men were selected for each treatment strategy. The 7-year cumulative incidence of PCa death decreased in all risk and treatment groups. For example, the incidence in men diagnosed with low-risk PCa and managed with observation was 1.2% in 2000-2005, which decreased to 0.4% in 2011-2016. Corresponding incidences for men with intermediate-risk PCa managed with observation were 2.0% and 0.7%. The relative risk of PCa death was lower in men with low-risk PCa managed with radical prostatectomy compared to observation: in 2000-2005 hazard ratio (HR) 0.20 (95% confidence interval [CI] 0.10-0.38) and in 2011-2016 HR 0.35 (95% CI 0.05-2.26). Corresponding risks for men with intermediate-risk PCa were HR 0.28 (95% CI 0.16-0.47) and HR 0.21 (95% CI 0.04-1.18). The absolute risk reduction of radical prostatectomy compared to observation for men with low-risk PCa was 1% in 2000-2005 and 0.4% in 2011-2016, and for men with intermediate-risk PCa 1.1% in 2000-2005 and 0.7% in 2011-2016. CONCLUSION: Men diagnosed in 2011-2016 with low-risk and favourable intermediate-risk PCa have a similar relative benefit but smaller absolute benefit of curative treatment compared to men diagnosed in 2000-200

Assessment of comorbidity is crucial for confounding adjustment and prediction of mortality in register-based studies, but the commonly used Charlson comorbidity index is not sufficiently predictive. We aimed to develop a multidimensional diagnosis-based comorbidity index (MDCI) that captures comorbidity better than the Charlson Comorbidity index. The index was developed based on 286,688 men free of prostate cancer randomly selected from the Swedish general population, and validated in 54,539 men without and 68,357 men with prostate cancer. All ICD-10 codes from inpatient and outpatient discharges during 10 years prior to the index date were used to define variables indicating frequency of code occurrence, recency, and total duration of related hospital admissions. Penalized Cox regression was used to predict 10-year all-cause mortality. The MDCI predicted risk of death better than the Charlson comorbidity index, with a c-index of 0.756 (95% confidence interval [CI] = 0.751, 0.762) vs 0.688 (95% CI = 0.683, 0.693) in the validation cohort of men without prostate cancer. Men in the lowest vs highest MDCI quartile had distinctively different survival in the validation cohort of men with prostate cancer, with an overall hazard ratio [HR] of 5.08 (95% CI = 4.90, 5.26). This was also consistent within strata of age and Charlson comorbidity index, e.g. HR = 5.90 (95% CI = 4.65, 7.50) in men younger than 60 years with CCI 0. These results indicate that comorbidity assessment in register-based studies can be improved by use of all ICD-10 codes and taking related frequency, recency, and duration of hospital admissions into account.