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Background It is unknown if a period of active surveillance before prostatectomy for prostate cancer (PCa) worsens functional outcomes. The aim of this study was to compare functional outcomes after primary vs delayed robot-assisted radical prostatectomy.Methods We included men registered in the National Prostate Cancer Register of Sweden with low and favorable intermediate-risk PCa who underwent robot-assisted prostatectomy in 2018-2020 and had filled a questionnaire on patient-reported outcome measures. Multivariable logistic regression analysis was used to compare the functional outcomes of primary and delayed prostatectomy.Results 2571 men underwent primary, and 921 men underwent delayed prostatectomy. Delayed prostatectomy was not associated with reduced overall quality of life (adjusted Odds Ratio [OR] 1.04; 95% confidence interval [CI] 0.71-1.55) or erectile dysfunction (adjusted OR 0.90, 95% CI 0.69-1.22). Urinary incontinence was slightly more common after delayed prostatectomy (15% vs 11%; adjusted OR 1.38, 95% CI 0.91-2.01). There were weak associations between time to prostatectomy and urinary symptoms and bother, with a 3% annual increase in the risk for urinary incontinence (adjusted OR 1.03; 95% CI 0.94-1.13).Conclusion These results suggest that a period on active surveillance before robot-assisted radical prostatectomy has little detrimental effect on functional outcomes. Since only around half of men on active surveillance will transit to prostatectomy, these outcomes represent a worst-case scenario for men who start active surveillance. These results support the use of active surveillance for men with low-risk and favorable intermediate-risk PCa.

Prostate cancer grade is currently often reported both by Gleason scores and by grouping of the scores into five socalled International Society of Urological Pathology (ISUP) grades (also known as grade groups). Using population-based registry data from 172,112 men diagnosed with prostate cancer on needle biopsy, we recently investigated the outcome of Gleason score 8-10 prostate cancer with death due to prostate cancer and death from any cause as endpoints. There was a prognostic heterogeneity between Gleason scores 3+5, 4+4 and 5+3 (ISUP grade 4) and between Gleason scores 4+5, 5+4 and 5+5 (ISUP grade 5). This heterogeneity was lost when the grades collapsed into ISUP grades 4 and 5, respectively. On the other hand, there was also a prognostic overlap between these ISUP grades. The outcome of Gleason score 5+3 and 4+5 cancers was very similar. The prostatespecific mortality of Gleason scores 5+3 and 4+5 was 0.32 (95% confidence interval 0.27-0.36) and 0.30 (0.29-0.31), respectively, after 5 years and 0.44 (0.39-0.49) and 0.45 (0.44-0.46), respectively, after 10 years. The findings emphasise the importance of reporting the Gleason grades and scores for more accurate prognostic information of highly heterogeneous high-grade prostate cancers. It also questions the clinical value of the current recommendations of grouping of Gleason scores into ISUP grades or grade groups.

Background: Inequity in prostate cancer detection can be assessed by relating the diagnostic intensity to the incidence rate of advanced disease in different population groups, according to factors such as socioeconomic status or ethnicity.

Methods: We used nationwide Swedish register data from Prostate Cancer data Base Sweden 5.0 and Statistics Sweden, which enabled us to estimate incidence rates of low-risk prostate cancer (a proxy for diagnostic activity) and advanced disease (locally advanced and/or metastatic) across population groups according to household income, country of birth, and neighborhood-level characteristics.

Results: We found a gradient in the age-standardized incidence of low-risk prostate cancer across income groups, from 60 per 100,000/year in men with high to 34 per 100,000/year in men with low household income: adjusted incidence rate ratio (IRR) 0.65 (95% confidence interval [CI] 0.59–0.71). The gradient in the incidence of advanced disease had the opposite direction, from 44 to 60 per 100,000/year, IRR 1.43 (95% CI 1.31–1.56). Immigrants from a non-Nordic country (nearly 40% from Asia) had lower incidence rates of both low-risk (IRR 0.47, 95% CI 0.42–0.53) and advanced disease (IRR 0.65, 95% CI 0.58–0.73) than men born in a Nordic country. Neighborhood-level analysis considering economic standard, share of immigrants, and degree of urbanization did not clearly differentiate the incidence of advanced disease.

Interpretation: Our results suggest that measures to facilitate early detection of prostate cancer should be targeted to men with a low income. A low diagnostic activity for prostate cancer among immigrants from countries with low background risk may not imply unjustified social disparity.

Background Obesity, assessed by body mass index (BMI), is an established risk factor for 13 cancers. We aimed toidentify further potential obesity-related cancers and to quantify their association with BMI relative to that ofestablished obesity-related cancers.

Methods Using Cox regression models on 4,142,349 individuals in Sweden (mean age 27.1 years at weight mea-surement), we calculated hazard ratios (HRs) for the association between BMI and the risk of 122 cancers and cancersubtypes, grouped by topography and morphology. Cancers with a positive association (i.e., HR >1) at an alpha-level of0.05 for obesity (BMI >= 30 kg/m(2)) vs. normal weight (BMI 18.5-24.9 kg/m(2)) or per 5 kg/m2higher BMI, for whichobesity is not an established risk factor, were considered potentially obesity related.

Findings After 100.2 million person-years of follow-up, 332,501 incident cancer cases were recorded. We identified 15cancers in men and 16 in women as potentially obesity related. These were cancers of the head and neck,gastrointestinal tract, malignant melanoma, genital organs, endocrine organs, connective tissue, andhaematological malignancies. Among these, there was evidence of differential associations with BMI betweensubtypes of gastric cancer, small intestine cancer, cervical cancer, and lymphoid neoplasms (P values forheterogeneity in HRs <0.05). The HR (95% confidence interval) per 5 kg/m(2)higher BMI was 1.17 (1.15-1.20) in men and 1.13 (1.11-1.15) in women for potential obesity-related cancers (51,690 cases), and 1.24 (1.22-1.26) in menand 1.12 (1.11-1.13) in women for established obesity-related cancers (84,384 cases).

Interpretation This study suggests a large number of potential obesity-related cancers could be added to alreadyestablished ones. Importantly, the magnitudes of the associations were largely comparable to those of the alreadyestablished obesity-related cancers. We also provide evidence of specific cancer subtypes driving some associationswith BMI. Studies accounting for cancer-specific confounders are needed to confirm thesefindings.

BACKGROUND: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited.

METHODS: We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index.

RESULTS: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death.

CONCLUSIONS: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.

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.