Rolf Gedeborg

Background and purpose: We aimed to describe temporal changes in diagnostic work-up, treatment, and prostate cancer (PCa) mortality in locally advanced PCa in 2016–2024 in Sweden. Patient/material and methods: Men registered in the National Prostate Cancer Register of Sweden in 2016–2024 with locally advanced PCa; clinical T stage 3–4, no distant metastases, and prostate-specific antigen < 100 ng/ml were included. We computed the proportion of use of prostate magnetic resonance imaging (MRI) before biopsy, radical prostatectomy, radical radiotherapy, androgen deprivation therapy, and abiraterone, and described the trend in PCa mortality across three calendar periods.Results: During the 9-year study period 7,484 men with locally advanced PCa were identified. Use of MRI before biopsy increased from 3% in 2016 to 73% in 2024. Concomitantly, radical treatment increased from 35% to 48%, entirely due to increased use of radiotherapy. Abiraterone was not used before 2022 but 31% received this treatment in 2024. The 3-year PCa mortality decreased from 8% (95% confidence interval [CI]: 7–9) in 2016–2018 to 6% (95% CI: 4–8) in 2022–2024. Interpretation: In this nationwide, population-based study of men with locally advanced PCa, the use of MRI before biopsy, radical radiotherapy, and treatment with abiraterone increased over time. These changes coincided with a modest decrease in 3-year PCa mortality.

Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is commonly used in cancer trials to select a study population with good performance, but ECOG-PS is rarely available in health-care registers. We assessed if patient age and comorbidity indices can substitute ECOG-PS when selecting men in register-based studies of advanced prostate cancer. ECOG-PS data for 3966 men on androgen deprivation therapy for prostate cancer were retrieved from Prostate Cancer data Base Sweden. Logistic regression models were used to discriminate between ECOG-PS 0–1 versus 2–4 based on age, Charlson comorbidity index (CCI), a novel Multidimensional Diagnosis-based Comorbidity Index (MDCI) based on ICD codes, and a Drug Comorbidity Index (DCI) based on filled prescriptions. The model based on age, MDCI, and DCI provided the best discrimination (AUC = 0.82; 95% CI 0.81–0.84). In a hypothetical cohort of 1000 men where 750 men had ECOG-PS 0–1, 600 men would be included when excluding those with high risk of ECOG-PS 2–4 using this model and 60 of these would have ECOG 2–4 instead of 250 men if all 1000 men had been included. Age and two new comorbidity indices can with reasonable precision substitute ECOG-PS and help identify subsets of study populations likely to have favourable ECOG-PS.

The Charlson Comorbidity Index (CCI) is widely used to control confounding factors in epidemiological studies. There is a need to characterize the performance of CCI in a contemporary general population. This study assessed the discriminative ability of CCI for long-term mortality in relation to age, sex, data source, length of look-back period, and calendar time. Open cohort study of all adults residing in Sweden for at least one year between 2003 and 2022. Multiple versions of the CCI were calculated based on 1–10 years of lookback in the Swedish National Patient Register. Discrimination was determined using the concordance index (C-index). Kaplan-Meier curves were used to describe 10-year survival. About 10395689 unique individuals had a median follow-up for mortality of 10 years. The C-index of CCI increased with the length of the look-back period, from 0.694 (95% confidence interval [CI], 0.694–0.694) at 1 year, to 0.784 (95% CI, 0.783–0.784) at 5 years, and to 0.808 (95% CI, 0.807–0.808) at 10 years. Discrimination was highest in subjects aged 60 years, for whom the discrimination of CCI_10years was higher in women (C-index, 0.794 [95% CI, 0.788–0.799]) than in men (C-index, 0.730 [95% CI, 0.725–0.735]). Within age strata above 70 years, the risk of death was much lower in subjects with CCI = 0 vs 1, 2 vs 3, and 3 vs ≥4, but not in those with CCI = 1 vs 2. The CCI discriminated risk of death best using a look-back period of at least 5 years and performed better in women than in men in most age groups. Our findings offer insights into both the practical utility of the CCI and the interpretation of studies in which it has been applied.

A family history of prostate cancer in first‐degree relatives is an established risk factor for prostate cancer, but the specific associations between prostate cancer characteristics in fathers and the risk of high‐risk prostate cancer in their sons remain unclear. We identified men in Prostate Cancer data Base Sweden whose fathers had been diagnosed with prostate cancer in 1998–2005. We compared the observed number of prostate cancer diagnoses in these men with the expected number in the Swedish male population, estimating standardized incidence ratios (SIR). The median age of the 25,287 included sons of men with prostate cancer was 52 years (interquartile range 47–57 years) at end of follow‐up. Their overall risk of a prostate cancer diagnosis was higher if the father had been diagnosed at less than 65 years old (SIR, 4.3, 95% confidence interval [CI], 3.8–5.0), compared with having a father diagnosed when 70 years old or older (SIR, 2.3; 95% CI 1.9–2.8). Sons of fathers diagnosed at less than 65 had a higher risk of Gleason score ≥8 cancers (SIR, 2.3; 95% CI 1.1–4.1) than sons of fathers diagnosed at 70 years old or older (SIR, 1.2; 95% CI 0.4–2.6). Having a father with a Gleason ≥8 cancer was associated with an increased risk for a Gleason ≥8 cancer (SIR, 2.6; 95% CI 1.1–5.1). These population‐based results suggest that the father's prostate cancer characteristics should be considered when counseling men on prostate‐specific antigen testing and diagnostic strategies.

Background:A family history (FH) of prostate cancer increases the risk of prostate cancer, but its association with prostate cancer mortality remains unclear.Methods:FH was defined as having a first-degree relative who was diagnosed before age 60 or died from prostate cancer. We used Cox regression to estimate associations between FH and prostate cancer characteristics at diagnosis, radical treatment, and prostate cancer death in men born after 1932 and diagnosed with prostate cancer between 1998 and 2020 in Sweden.Results:Among 125,272 men with prostate cancer, 13,193 had an FH of early onset or lethal prostate cancer. At diagnosis, men with FH had 1.4 years lower median age, 0.87 ng/mL lower serum PSA, lower proportion of Gleason score 8 to 10 cancer (14.8% vs. 17.6%), lower odds for metastatic disease [OR, 0.79; 95% confidence interval (CI), 0.73–0.86], and higher odds for radical treatment (OR, 1.25; 95% CI, 1.18–1.32). With a median follow-up of 6.9 years and 12,773 prostate cancer deaths, mortality was lower (crude HR, 0.77; 95% CI, 0.73–0.82) in men with FH. Adjustment for prostate cancer characteristics attenuated this association (adjusted HR, 0.94; 95% CI, 0.88–1.00).Conclusions:Men with prostate cancer and an FH of early onset or lethal prostate cancer had more favorable cancer characteristics, a higher likelihood of radical treatment, and similar prostate cancer mortality compared with men without an FH.Impact:In men with prostate cancer, the risk of prostate cancer death seems unaffected by an FH of early onset or lethal prostate cancer after controlling for clinical characteristics. More research is needed on the potential role of screening.

Results of sensitivity analysis where exposure was handled as a time-varying covariate, i.e., handle the situation if father or a brother was diagnosed with PCa after the man in the study was diagnosed with PCa.

Results of sensitivity analysis restricted to men diagnosed before January 1, 2010.

The table describes details of family history in the study population, comparing men with and without early onset (age <60 years) or lethal prostate cancer in at least one first-degree relative.

A Directed Acyclic Graph (DAG) describing a hypothesized causal structure between family history of prostate cancer and prostate cancer death