Target trial emulation using new comorbidity indices provided risk estimates comparable to a randomized trial.

OBJECTIVES: To quantify the ability of two new comorbidity indices to adjust for confounding, by benchmarking a target trial emulation against the randomized controlled trial (RCT) result. STUDY DESIGN AND SETTING: Observational study including 18,316 men from Prostate Cancer data Base Sweden 5.0, diagnosed with prostate cancer between 2008 and 2019 and treated with primary radical prostatectomy (RP, n = 14,379) or radiotherapy (RT, n = 3,937). The effect on adjusted risk of death from any cause after adjustment for comorbidity by use of two new comorbidity indices, the multidimensional diagnosis-based comorbidity index and the drug comorbidity index, were compared to adjustment for the Charlson comorbidity index (CCI). RESULTS: Risk of death was higher after RT than RP (hazard ratio [HR] = 1.94; 95% confidence interval [CI]: 1.70-2.21). The difference decreased when adjusting for age, cancer characteristics, and CCI (HR = 1.32, 95% CI: 1.06-1.66). Adjustment for the two new comorbidity indices further attenuated the difference (HR 1.14, 95% CI 0.91-1.44). Emulation of a hypothetical pragmatic trial where also older men with any type of baseline comorbidity were included, largely confirmed these results (HR 1.10; 95% CI 0.95-1.26). CONCLUSION: Adjustment for comorbidity using two new indices provided comparable risk of death from any cause in line with results of a RCT. Similar results were seen in a broader study population, more representative of clinical practice.

Natural History of Nonmetastatic Prostate Cancer Managed With Watchful Waiting.

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.

Risk of prostate cancer death in men diagnosed with prostate cancer at cystoprostat-ectomy. A nationwide population-based study.

BACKGROUND AND AIMS: One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up. METHODS: Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register. RESULTS: Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death. CONCLUSIONS: For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.

Temporal trend in risk of prostate cancer death in men with favourable-risk prostate cancer.

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 2000-2005.

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

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.

Prognosis of Gleason score 8 prostatic adenocarcinoma in needle biopsies: a nationwide population-based study.

A 5-tier grouping of Gleason scores has recently been proposed. Studies have indicated prognostic heterogeneity within these groups. We assessed prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) for men diagnosed with Gleason score 3 + 5 = 8, 4 + 4 = 8 and 5 + 3 = 8 acinar adenocarcinoma on needle biopsy in a population-based national cohort. The Prostate Cancer data Base Sweden 5.0 was used for survival analysis with PCSM and ACM at 5 and 10 years as endpoints. Multivariable Cox regression models controlling for socioeconomic factors, stage and primary treatment type were used for PCSM and ACM. Among 199,620 men reported with prostate cancer in 2000-2020, 172,112 were diagnosed on needle biopsy. In 18,281 (11%), there was a Gleason score of 8 in needle biopsies, including a Gleason score of 3 + 5, 4 + 4 and 5 + 3 in 11%, 86% and 2.3%, respectively. The primary treatment was androgen deprivation therapy (55%), deferred treatment (8%), radical prostatectomy (16%) or radical radiotherapy (21%). PCSM in men with Gleason scores of 3 + 5, 4 + 4 and 5 + 3 at 5 years of follow-up was 0.10 (95% CI 0.09-0.12), 0.22 (0.22-0.23) and 0.32 (0.27-0.36), respectively, and at 10 years 0.19 (0.17-0.22), 0.34 (0.33-0.35) and 0.44 (0.39-0.49), respectively. There was a significantly higher PCSM after 5 and 10 years in men with Gleason score 5 + 3 cancers than in those with 4 + 4 and in Gleason score 4 + 4 cancers than in those with 3 + 5. Grouping of Gleason scores will eliminate the prognostic granularity of Gleason scoring, thus diminishing the prognostic significance of this proposed grading system.

Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 - a case-control study.

OBJECTIVE: To examine associations between objective signs of progression (triggers) and transition from active surveillance (AS) to radical treatment for prostate cancer (PC). PATIENTS AND METHODS: This case-control study included men with low- or favourable intermediate-risk PC in the region of Halland, with data from The National Prostate Cancer Register (NPCR), Sweden, starting AS between 2008 and 2020. Cases were men who transitioned to radical treatment. For each case, 10 controls who remained in AS were selected without further matching. Triggers for transition to treatment were histopathological progression, magnetic resonance imaging (MRI) progression and increases in prostate-specific antigen (PSA) levels. We compared the probabilities for triggers between cases and controls, in 2008-2014 and 2015-2020, using logistic regression. RESULTS: Amongst 846 men, we identified 98 cases in 2008-2014 and 172 cases in 2015-2020. Histopathological progression was associated with transition, most strongly in the later period (2008-2014: odds ratios [OR] 6.88, 95% confidence interval [CI] 3.69-12.80; and 2015-2020: OR 75.29, 95% CI 39.60-143.17). MRI progression was associated with transition in 2015-2020 (OR 6.38, 95% CI 2.70-15.06), whereas an increase in PSA was weakly associated with transition in the early period. The absence of triggers was associated with no transition (2008-2014: OR 0.24, 95% CI 0.15-0.40, and 2015-2020: OR 0.09, 95% CI 0.06-0.14). The probability of no trigger was 27% in cases 2015-2020. CONCLUSION: The increase in association between histopathological trigger and transition to treatment indicates increased quality of AS. Still, amongst men treated from 2015 to 2020, 27% transitioned without any trigger.

Immune cell infiltrate in ductal carcinoma in situ and the risk of dying from breast cancer: case-control study.

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.

Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

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.

Patient-reported Side Effects 1 Year After Radical Prostatectomy or Radiotherapy for Prostate Cancer: A Register-based Nationwide Study.

BACKGROUND: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, population-based cohorts. OBJECTIVE: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot-assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient-reported outcome measures in the Swedish prostate cancer database. DESIGN, SETTING, AND PARTICIPANTS: This was a nationwide, population-based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics. RESULTS AND LIMITATIONS: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19-0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61). CONCLUSIONS: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP. PATIENT SUMMARY: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects.

Development and validation of a multi-dimensional diagnosis-based comorbidity index that improves prediction of death in men with prostate cancer: Nationwide, population-based register study.

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.

Association of clinicopathologic variables and patient preference with the choice of surgical treatment for early-stage breast cancer: A registry-based study.

INTRODUCTION: Observational studies suggest that breast conserving surgery (BCS) and radiotherapy (RT) offers superior survival compared to mastectomy. The aim was to compare patient and tumour characteristics in women with invasive breast cancer ≤30 mm treated with either BCS or mastectomy, and to explore the underlying reason for choosing mastectomy. METHODS: Women registered with breast cancer ≤30 mm and ≤4 positive axillary lymph nodes in the Swedish National Breast Cancer Register 2013-2016 were included. Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy vs. BCS. RESULTS: Of 1860 breast cancers in 1825 women, 1346 were treated by BCS and 514 by mastectomy. Adjuvant RT was given to 1309 women (97.1 %) after BCS and 146 (27.6 %) after mastectomy. Variables associated with receiving a mastectomy vs. BCS included clinical detection (Odds Ratio (OR) 4.15 (95 % Confidence Interval (CI) 3.35-5.14)) and clinical stage (T2 vs. T1 (OR 3.68 (95 % CI 2.90-4.68)), N1 vs. N0 (OR 2.02 (95 % CI 1.38-2.96)). Women receiving mastectomy more often had oestrogen receptor negative, HER2 positive tumours of higher histological grade. The most common reported reason for mastectomy was large or multifocal tumours (53.5 %), followed by patient preference (34.5 %). CONCLUSION: Choice of surgery is strongly associated with key prognostic factors among women undergoing BCS with RT compared to mastectomy. Failure to control for all relevant confounders may bias results in outcome studies in favour of BCS.

Prognosis of Gleason Score 9-10 Prostatic Adenocarcinoma in Needle Biopsies: A Nationwide Population-based Study.

BACKGROUND: Since 2014, prostate cancer is reported using five-tier grouping of Gleason scores. Studies have suggested prognostic heterogeneity within the groups. OBJECTIVE: We assessed the risk of prostate cancer death for men diagnosed with Gleason scores 4 + 5, 5 + 4, and 5 + 5 on needle biopsy in a population-based cohort. DESIGN, SETTING, AND PARTICIPANTS: We used the data from Prostate Cancer data Base Sweden (PCBaSe) 4.0 for a survival analysis. Among 199 620 men reported to have prostate cancer in 2000-2020, 172 112 were diagnosed on needle biopsy. The primary treatment was classified as androgen deprivation therapy (66%), deferred treatment (5%), radical prostatectomy (7%), or radical radiotherapy (21%). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The risks of death from prostate cancer in men with Gleason score 9-10 at 5 and 10 yr were used as endpoints. Multivariable Cox regression models controlling for socioeconomic factors and primary treatment were used for time-to-event analyses of death from prostate cancer and death from any causes. RESULTS AND LIMITATIONS: A total of 20 419 (12%) men had a Gleason score of 9-10, including Gleason scores of 4 + 5, 5 + 4, and 5 + 5 in 14 333 (70%), 4223 (21%), and 1863 (9%) men, respectively. The risks of prostate cancer death for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr of follow-up were 0.45 (confidence interval [CI] 0.44-0.46), 0.56 (0.55-0.58), and 0.66 (0.63-0.68), respectively. The risks of death of any cause for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr were 0.73 (CI 0.72-0.74), 0.81 (0.80-0.83), and 0.87 (0.85-0.89), respectively. CONCLUSIONS: We demonstrate in the largest and most complete cohort analyzed to date that collapsing the Gleason scores by grouping results in loss of prognostic information in men with Gleason score 9-10 cancer. PATIENT SUMMARY: Survival of prostate cancer patients with the highest tumor grades varies depending on grade composition.

Uptake of doublet therapy for de novo metastatic castration sensitive prostate cancer: a population-based drug utilisation study in Sweden.

BACKGROUND: Randomised controlled trials have demonstrated prolonged survival with new upfront treatments in addition to standard androgen deprivation therapy (ADT) in men with de novo metastatic castration-sensitive prostate cancer. We describe patient characteristics, time trends and regional differences in uptake of these new treatment strategies in clinical practice. MATERIAL AND METHODS: This descriptive study consisted of men registered in the National Prostate Cancer Register of Sweden from 1 January 2018 to 31 March 2022 with de novo metastatic castration-sensitive prostate cancer defined by the presence of metastases on imaging at the time of diagnosis. Life expectancy was calculated based on age, Charlson Comorbidity Index and a Drug Comorbidity Index. RESULTS: Within 6 months from diagnosis, 57% (1,677/2,959) of men with de novo metastatic castration-sensitive prostate cancer and more than 3 years of life expectancy had received docetaxel, abiraterone, enzalutamide, apalutamide and/or radiotherapy. Over time, there was a 2-fold increase in uptake of any added treatment, mainly driven by a 6-fold increase in use of abiraterone, enzalutamide or apalutamide, with little change in use of other treatments. CONCLUSIONS: Slightly more than half of men diagnosed with de novo metastatic castration-sensitive prostate cancer and a life expectancy of at least 3 years received additions to standard ADT as recommended by national guidelines in 2019-2022 in Sweden. There was a 2-fold increase in use of these treatments during the study period; however, efforts to further increase adherence to guidelines are warranted.

Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists.

BACKGROUND: Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT. MATERIALS AND METHODS: Data for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan-Meier plots and Cox proportional hazard models adjusted for putative confounders. RESULTS: Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50-1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65-2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37-1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42-3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26-1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88-8.77) vs the reference. CONCLUSION: In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT.

Survival Trend in Individuals With De Novo Metastatic Prostate Cancer After the Introduction of Doublet Therapy.

Importance: Recently, life-prolonging treatments for patients with advanced prostate cancer have been introduced in clinical practice. Objective: To investigate if the introduction of doublet therapy is associated with changes in survival on a population-basis. Design, Setting, and Participants: This nationwide population-based cohort study used data from the Prostate Cancer data Base Sweden from 2008 to 2020. Men registered with de novo metastatic castration-sensitive prostate cancer (mCSPC) were included. Exposure: The proportion of men with mCSPC who received doublet therapy, ie, androgen deprivation therapy plus androgen receptor pathway inhibitor drugs or chemotherapy was assessed. Main Outcomes and Measures: Standardized overall survival, taking age, comorbidity, and cancer characteristics into consideration, was estimated by use of a parametric survival model. Results: A total of 11 382 men were included in this study (median [IQR] age, 74.0 [68-81] years). There was a shift toward less advanced prostate cancer during the study period with a decrease in median (IQR) prostate-specific antigen at diagnosis in men with mCSPC from 145 (39-571) ng/mL to 107 (27-426) ng/mL. Upfront treatment with doublet therapy in these men simultaneously increased from 1% (7 of 991) in 2016 to 44% (402 of 922) in 2020. The adjusted 5-year overall survival increased from 26% (95% CI, 25%-28%) from 2008 to 2012 to 35% (95% CI, 31%-40%) from 2017 to 2020. During the first 5 years after diagnosis, there was an increase in mean survival of 6 months, from 2.7 (95% CI, 2.6-2.8) years from 2008 to 2012 to 3.2 (95% CI, 3.1-3.1) years from 2017 to 2020. Conclusions and Relevance: In parallel with improvements in treatment of advanced prostate cancer, a clinically meaningful increase in mean survival was observed in men with de novo mCSPC in Sweden between 2008 and 2020 in this study.

Angiosarcoma in the breast: a population-based cohort from Sweden.

BACKGROUND: Breast angiosarcoma is a rare disease mostly observed in breast cancer (BC) patients who have previously received radiotherapy (RT). Little is known about angiosarcoma aetiology, management, and outcome. The study aim was to estimate risk and to characterize breast angiosarcoma in a Swedish population-based cohort. METHODS: The Swedish Cancer Registry was searched for breast angiosarcoma between 1992 and 2018 in three Swedish healthcare regions (population 5.5 million). Information on previous BC, RT, management, and outcome were retrieved from medical records. RESULTS: Overall, 49 angiosarcomas located in the breast, chest wall, or axilla were identified, 8 primary and 41 secondary to BC treatment. Median age was 51 and 73 years, respectively. The minimum latency period of secondary angiosarcoma after a BC diagnosis was 4 years (range 4-21 years). The cumulative incidence of angiosarcoma after breast RT increased continuously, reaching 1.4‰ after 20 years. Among 44 women with angiosarcoma treated by surgery, 29 developed subsequent local recurrence. Median recurrence-free survival was 3.4 and 1.8 years for primary and secondary angiosarcoma, respectively. The 5-year overall survival probability for the whole cohort was 50 per cent (95 per cent c.i., 21 per cent-100 per cent) for primary breast angiosarcoma and 35 per cent (95 per cent c.i., 23 per cent-54 per cent) for secondary angiosarcoma. CONCLUSION: Breast angiosarcoma is a rare disease strongly associated with a history of previous BC RT. Overall survival is poor with high rates of local recurrences and distant metastasis.

Frequency of Biopsy and Tumor Grade Before vs After Introduction of Prostate Magnetic Resonance Imaging.

Importance: In randomized clinical trials (RCTs), magnetic resonance imaging (MRI) before prostate biopsy has been associated with fewer biopsies, decreased detection of Gleason score 6 cancers, and increased detection of Gleason score 7 or higher cancers. Objective: To study whether MRI of the prostate before the decision to biopsy is associated with biopsy frequency and distribution of Gleason score in clinical practice. Design, Setting, and Participants: This is a retrospective, population-based cohort study of men in Jönköping Region, Sweden. Men with prostate-specific antigen (PSA) level measured between November 2011 and 2020 were monitored until January 31, 2021. Men with known prostate cancer were excluded. Data analysis was performed from July to December 2022. Exposures: Data on repeated PSA measures, prostate biopsies, and MRI prostate were extracted from health care records, and cancer characteristics were obtained from The National Prostate Cancer Register. Main Outcomes and Measures: The proportions of men who underwent prostate biopsy and risk of Gleason score 6 or Gleason score 7 or higher cancer and negative biopsy before and after introduction of MRI were calculated. Results: In this cohort study of 23 802 men (mean [SD] age, 60.8 [13.6] years) who underwent PSA testing, when the use of MRI increased, fewer biopsies were performed (adjusted odds ratio [OR], 0.84; 95% CI, 0.72-0.97) and the odds of detecting Gleason score 6 cancer decreased (OR, 0.47; 95% CI, 0.33-0.64), whereas the odds of detecting Gleason score 7 or higher cancer increased (OR, 1.24; 95% CI, 1.02-1.50). Conclusions and Relevance: In this study, the introduction of MRI to clinical practice was associated with a decreased proportion of men who underwent a biopsy and decreased detection of Gleason score 6 cancer but increased detection of Gleason score 7 or higher cancer. These clinical data support the use of prostate MRI before biopsy in an effort to avoid unnecessary biopsies.

Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes.

Background: Regional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies. Objective: To examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death. Design setting and participants: A Swedish population-based cohort study was conducted including men in the National Prostate Cancer Register in Sweden with low-risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019. Intervention: Regional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysis: Probabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed. Results and limitations: We included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0-7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI -0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting. Conclusions: A regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment. Patient summary: There are considerable regional differences in active surveillance (AS) uptake for prostate cancer. This study compared the outcomes of AS in different regions and found no association between AS uptake and failure of AS; it suggests that a low AS uptake indicates overtreatment.