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.

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.

Evidence of cancer progression as the cause of death in men with prostate cancer in Sweden.

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.

Diagnostic activity impacts lifetime risk of prostate cancer diagnosis more strongly than life expectancy.

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.

Comparison of Relative Survival and Cause-Specific Survival in Men With Prostate Cancer According to Age and Risk Category: A Nationwide, Population-Based Study.

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.

Short- and long-term mortality after deep sternal wound infection following cardiac surgery: experiences from SWEDEHEART.

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.

Changes in treatment and mortality in men with locally advanced prostate cancer between 2000 and 2016: a nationwide, population-based study in Sweden.

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.

Long-term outcomes after coronary artery bypass surgery in patients with diabetes.

OBJECTIVES: Our aim was to investigate the outcome of patients with diabetes undergoing coronary artery bypass grafting (CABG) surgery in a whole population with main focus on long-term mortality and complications. METHODS: This was a nationwide retrospective analysis of all patients who underwent isolated primary CABG in Iceland between 2001 and 2016. Overall survival together with the composite end point of major adverse cardiac and cerebrovascular events was compared between patients with diabetes and patients without diabetes during a median follow-up of 8.5 years. Multivariable regression analyses were used to evaluate the impact of diabetes on both short- and long-term outcomes. RESULTS: Of a total of 2060 patients, 356 (17%) patients had diabetes. Patients with diabetes had a higher body mass index (29.9 vs 27.9 kg/m2) and more often had hypertension (83% vs 62%) and chronic kidney disease (estimated glomerular filtration rate ≤60 ml/min/1.73 m2, 21% vs 14%). Patients with diabetes had an increased risk of operative mortality [odds ratio 2.52, 95% confidence interval (CI) 1.27-4.80] when adjusted for confounders. 5-Year overall survival (85% vs 91%, P < 0.001) and 5-year freedom from major adverse cardiac and cerebrovascular events were also inferior for patients with diabetes (77% vs 82%, P < 0.001). Cox regression analysis adjusting for potential confounders showed that the diagnosis of diabetes significantly predicted all-cause mortality [hazard ratio (HR) 1.87, 95% CI 1.53-2.29] and increased risk of major adverse cardiac and cerebrovascular events (HR 1.47, 95% CI 1.23-1.75). CONCLUSIONS: Patients with diabetes have significantly lower survival after CABG, both within 30 days and during long-term follow-up.

Improved long-term survival following pulmonary resections for non-small cell lung cancer: results of a nationwide study from Iceland.

BACKGROUND: We studied the outcome of pulmonary resection with curative intent for non-small cell lung cancer (NSCLC) in a nationwide study covering a 24-year period, focusing on survival. METHODS: All patients who underwent pulmonary resection for NSCLC in Iceland in the period 1991-2014 were reviewed for demographics, TNM stage and survival. Median length of follow-up was 45 months. Three 8-year periods were compared, overall survival was estimated, and prognostic factors for survival were identified. RESULTS: Altogether, 652 surgical resections were performed on 644 individuals (52% females): 492 lobectomies (75%), 77 pneumonectomies (12%), and 83 sublobar resections (13%). Mean age increased from 65 to 68 yrs during the study period (P=0.002). The number of cases operated at stage IA increased substantially between the first and last periods (29% vs. 37%; P<0.001). Survival improved from 75% to 88% at 1 year and from 38% to 53% at 5 years (P<0.001). Independent prognostic factors for mortality were advanced TNM stage (HR =2.68 for stage IIIA vs. I), age (HR =1.04), ischaemic heart disease (HR =1.26), any minor complication (HR =1.26), and sublobar resection (HR =1.33), but surgical margins free from tumour growth (HR =0.59) and treatment during the latter two eight-year periods were predictors of lower mortality. The best survival was seen between 2007 and 2014 (HR =0.61, 95% CI: 0.48-0.78; P<0.001). CONCLUSIONS: Survival of patients who have undergone pulmonary resection for NSCLC has improved significantly in Iceland. This may be explained by the increased number of patients diagnosed at lower stages and improved preoperative staging, with fewer understaged patients.

Resection rate and operability of elderly patients with non-small cell lung cancer: Nationwide study from 1991 to 2014.

OBJECTIVES: An increasing number of elderly patients are diagnosed with non-small cell lung cancer (NSCLC). We compared the surgical resection rate, operability and survival in this age group (≥75 years) to younger patients using centralized databases in Iceland. METHODS: The study population comprised all patients diagnosed with NSCLC in Iceland from 1991 to 2014. A total of 140 elderly patients (≥75 years) with NSCLC underwent pulmonary resection and were compared with 550 surgically resected patients less than 75 years, with respect to resection rate, short and long-term survival and complications of surgery. Reasons for exclusion from surgery were registered for elderly surgical candidates (stages IA-IIB). RESULTS: Surgical resection rate in the elderly group was 18% compared to 32% in the younger age group ( P < 0.001). The most frequent reasons for not operating on elderly patients in stages IA-IIB were poor pulmonary function (58%), heart disease (17%) or multiple comorbidities (17%). The rate of major complications following surgery was comparable in the elderly versus the younger age group, 13 vs 11%, respectively ( P = 0.578). The same was true for 30 day mortality (2 vs 1%, P = 0.397). Five-year overall survival was 40% vs 44% ( P = 0.019) and cancer-specific survival 51% vs 50% ( P = 0.802). CONCLUSIONS: Elderly patients with resectable NSCLC according to stage are frequently excluded from surgery due to comorbid conditions. Although the operated patients may represent a selected group, their favourable 30-day and long-term survival indicate that more elderly patients with NSCLC could be operated on.