Objective
To assess the strength of the evidence indicative of prostate cancer (PCa) progression as the adjudicated cause of death, according to age at death and PCa risk category.
Patients and ...Methods
Using data from the Prostate Cancer data Base Sweden, we identified a study frame of 5543 men with PCa registered as the cause of death according to the Cause of Death Register. We assessed the evidence of PCa progression through a review of healthcare records for a stratified sample of 495/5543. We extracted data on prostate‐specific antigen levels, presence of metastases on imaging, and PCa treatments, and quantified the evidence of disease progression using a points system.
Results
Both no evidence and moderate evidence for PCa progression was more common in men aged >85 years at death than those aged <85 years (29% vs 14%). Among the latter, the proportion with no evidence or moderate evidence for PCa progression was 21% for low‐risk, 14% for intermediate‐risk, 8% for high‐risk, and 0% for metastatic PCa. In contrast, in men aged >85 years, there was little difference in the proportion with no evidence or moderate evidence of PCa progression between PCa risk categories; 31% for low‐risk, 29% for intermediate‐risk, 29% for high‐risk, and 21% for metastatic PCa. Of the 5543 men who died from PCa, 13% (95% confidence interval 5–19%) were estimated to have either no evidence or moderate evidence of PCa progression.
Conclusions
Weak evidence for PCa progression as cause of death was more common in older men with PCa and in those with low‐risk PCa. This has implications for interpretation of mortality statistics especially when assessing screening and early treatment of PCa because the beneficial effect of earlier diagnosis could be masked by erroneous adjudication of PCa as cause of death in older men, particular those with localised disease at diagnosis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract
Net survival, estimated in a relative survival (RS) or cause-specific survival (CSS) framework, is a key measure of the effectiveness of cancer management. We compared RS and CSS in men with ...prostate cancer (PCa) according to age and risk category, using Prostate Cancer data Base Sweden, including 168,793 men younger than age 90 years, diagnosed 1998–2016 with PCa. RS and CSS were compared according to age and risk category based on TNM (tumor, nodes, and metastases) stage, Gleason score, and prostate-specific antigen level. Each framework requires assumptions that are unlikely to be appropriate for PCa. Ten-year RS was substantially higher than CSS in men aged 80–89 with low-risk PCa: 125% (95% confidence interval: 113, 138) versus 85% (95% confidence interval: 82, 88). In contrast, RS and CSS were similar for men under age 70 and for all men with regional or distant metastases. Both RS and CSS produce biased estimates of net survival for men with low- and intermediate-risk PCa, in particular for men over 80. Due to biases, net survival is overestimated in analysis of RS but underestimated in analysis of CSS. These results highlight the importance of evaluating the underlying assumptions for each method, because the “true” net survival is expected to lie between the limits of RS and CSS.
The main aim of the study was to determine the impact of diagnostic activity and life expectancy on the lifetime risk of a prostate cancer diagnosis. We used a state transition simulation model based ...on Swedish population-based data to simulate life trajectories for 2,000,000 men from age 40 to 100 in order to estimate the lifetime risk of a prostate cancer diagnosis. Risk estimates were determined by the level of diagnostic activity and estimated life expectancy. Higher exposure to diagnostic activity resulted in more prostate cancer diagnoses. This was especially true for men diagnosed with low or intermediate grade disease. Men exposed to high diagnostic compared to low diagnostic activity had a five-fold increased lifetime risk (22% vs. 5%) of being diagnosed with a low or intermediate-risk prostate cancer and half the risk of being diagnosed with a high-risk prostate cancer (6% vs. 13%). Men with a long life expectancy had a higher lifetime risk of a prostate cancer diagnosis both overall (21% vs. 15%) and in all risk categories when compared to men with a short life expectancy. The lifetime risk of a prostate cancer diagnosis is strongly influenced by diagnostic activity and to a lesser degree by life expectancy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
The main aim of the study was to determine the impact of diagnostic activity and life expectancy on the lifetime risk of a prostate cancer diagnosis. We used a state transition simulation model based ...on Swedish population-based data to simulate life trajectories for 2,000,000 men from age 40 to 100 in order to estimate the lifetime risk of a prostate cancer diagnosis. Risk estimates were determined by the level of diagnostic activity and estimated life expectancy. Higher exposure to diagnostic activity resulted in more prostate cancer diagnoses. This was especially true for men diagnosed with low or intermediate grade disease. Men exposed to high diagnostic compared to low diagnostic activity had a five-fold increased lifetime risk (22% vs. 5%) of being diagnosed with a low or intermediate-risk prostate cancer and half the risk of being diagnosed with a high-risk prostate cancer (6% vs. 13%). Men with a long life expectancy had a higher lifetime risk of a prostate cancer diagnosis both overall (21% vs. 15%) and in all risk categories when compared to men with a short life expectancy. The lifetime risk of a prostate cancer diagnosis is strongly influenced by diagnostic activity and to a lesser degree by life expectancy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To evaluate whether the effects of radical treatment in men with locally advanced prostate cancer (PCa) on PCa mortality observed in randomised clinical trials are applicable on a ...population basis.
Patients and methods
We conducted a population‐based cohort study using the Prostate Cancer data Base Sweden of 20 350 men diagnosed between 2000 and 2016 with locally advanced PCa, defined as clinical local stage T3/T4, M0, Mx and a prostate‐specific antigen level of <100 ng/mL. Cumulative PCa mortality was examined using competing risk analysis of all men with locally advanced PCa, and also including men who did not undergo radical treatment. Multivariate regression analysis, including prognostic factors, was used to calculate hazard ratios (HRs) for all‐cause and PCa‐specific death.
Results
The proportion of men treated with primary radical radiotherapy (n = 4174) or prostatectomy (n = 1210) increased from 15% in 2000–2003, 25% in 2004–2007, 33% in 2008–2011 to 43% in 2012–2016. The corresponding 5‐year PCa mortality decreased from 19%, 18%, 17%, to 15% for all men, with the steepest decrease in men aged 65–74 years, from 16% to 8%. The risk of PCa mortality in men aged <80 years was lower in the last period compared to the first period, with a HR of 0.65 (95% confidence interval 0.56–0.76) in multivariate analysis.
Conclusions
The threefold increase in use of radical treatment was accompanied by a modest decrease in PCa mortality in all men with newly diagnosed locally advanced PCa. For men aged 65–74 years, there was a 50% decrease in the relative risk of PCa death. This indicates that the benefits previously observed in randomised trials can also be achieved in a real‐life setting.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES: Deep sternal wound infection (DSWI) is a serious complication after open-heart surgery. We investigated the association between DSWI and short- and long-term all-cause mortality in a ...large well-defined nationwide population. METHODS: A retrospective, nationwide cohort study, which included 114676 consecutive patients who underwent coronary artery bypass grafting (CABG) and/or valve surgery from 1997 to 2015 in Sweden. Short- and long-term mortality was compared between DSWI patients and non-DSWI patients using propensity score inverse probability weighting adjustment based on patient characteristics and comorbidities. Median follow-up was 8.0 years (range 0-18.9). RESULTS: Altogether, 1516 patients (1.3%) developed DSWI, most commonly in patients undergoing combined CABG and valve surgery (2.1%). DSWI patients were older and had more disease burden than non-DSWI patients. The unadjusted cumulative mortality was higher in the DSWI group compared with the non-DSWI group at 90 days (7.9% vs 3.0%, P < 0.001) and at 1 year (12.8% vs 4.5%, P < 0.001). The adjusted absolute difference in risk of death was 2.3% 95% confidence interval (CI): 0.8-3.9 at 90 days and 4.7% (95% CI: 2.6-6.7) at 1 year. DSWI was independently associated with 90-day adjusted relative risk (aRR) 1.89 (95% CI: 1.38-2.59), 1-year aRR 2.13 (95% CI: 1.68-2.71) and long-term all-cause mortality adjusted hazard ratio 1.56 (95% CI: 1.30-1.88). CONCLUSIONS: Both short- and long-term mortality risks are higher in DSWI patients compared to non-DSWI patients. These results stress the importance of preventing these infections and careful postoperative monitoring of DSWI patients.
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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