Umeå University's logo

The International Bladder Cancer Group (IBCG) has proposed a prognostic model for intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) for clinical decision-making. We applied the IBCG IR model in a population-based Swedish setting in patients with primary IR NMIBC diagnosed 2013-2014 in BladderBaSe 2.0. Patients were stratified into low-risk (unifocal and tumour size < 3 cm) and intermediate-risk (multiple and/or tumour size ≥ 3 cm) for estimation of 1- and 3-year recurrence-free survival (RFS). Among 710 patients with IR NMIBC, 329 (46%) and 381 (54%) were categorized as low- and intermediate-risk, respectively. Probabilities of disease recurrence or death at 1 and 3 years in low-risk patients were 19% (95% confidence interval [CI]: 15-23) and 41% (95% CI: 35-46), versus 27% (95% CI: 22-31) and 45% (95% CI: 40-50) in the intermediate-risk group. In a sensitivity analysis including only patients receiving serial adjuvant instillations (n = 152) the corresponding probabilities at 1 and 3 years were 19% (95% CI: 10-28) and 33% (95% CI: 22-43) versus 15% (95% CI: 7-23) and 31% (95% CI: 20-41), respectively. Thus, no clinically meaningful difference in recurrence-free survival was observed between International Bladder Cancer Group low- and intermediate-risk groups in this population-based primary non-muscle invasive bladder cancer setting.

Purpose. To quantify the risk of clinically overt venous thromboembolism (VTE) and major bleeding (MB) during the first year following surgery for lumbar spinal stenosis (LSS) relative to a matched population cohort.

Methods: This nationwide, retrospective cohort study utilized data from the Swedish National Spine Register (Swespine), including 77,145 patients who underwent surgical treatment for LSS between 2003 and 2023. These patients were matched 1:5 to 385,388 referents from the general population. Outcomes (VTE and MB) were identified through cross-linkage with the National Patient Register (NPR) and the Swedish Stroke Register (Riksstroke). Adjusted Cox piecewise regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE and MB across prespecified postoperative intervals.

Results: Within the first 30 days after inclusion, patients exhibited substantially higher incidence rates of venous thromboembolism (VTE) and major bleeding (MB) compared with referents. The incidence rate of VTE was 30.39 per 1,000 person-years among patients versus 8.14 among referents, while the corresponding rates for MB were 88.78 and 31.87 per 1,000 person-years, respectively. Compared with referents, patients had a HR of 3.68 (95% CI, 3.05-4.44) for VTE and a HR of 2.52 (95% CI 2.27-2.80) for MB within the first 30 days after inclusion. The risk for VTE remained elevated through the 31–60-day interval (HR 2.09; 95% CI, 1.63-2.69), whereas the risk for MB declined sharply after the first month (HR 1.02; 95% CI 0.87-1.21).

Conclusion: Patients undergoing surgery for LSS face a significantly higher risk for VTE and MB compared to a matched population. This hazard was most acute during the first 30 postoperative days. While these risks decline sharply thereafter, the risk of VTE remains significantly elevated during the first 2 months following LSS surgery.

This nationwide register-based cohort study examined the association between castration status and postoperative survival in men who had undergone surgery for spinal metastases from prostate cancer. Bone metastases are common in prostate cancer, with the spine being the most frequent site. Using data from the Swedish Spine Register (Swespine) and Prostate Cancer Database Sweden (PCBaSe), 306 men with prostate cancer who underwent spinal surgery were identified. In total, 81 were categorized as castration-sensitive and 225 as castration-resistant disease at the time of spinal surgery. Postoperative survival was estimated using Kaplan-Meier analysis and compared with the log-rank test. Multivariable Cox regression was used to adjust for potential confounders. Median survival after surgery was significantly longer in men with castration-sensitive prostate cancer (33 months, IQR 15-55) compared to those with castration-resistant disease (8 months, IQR 5-31; p < 0.001). Castration-sensitive status was independently associated with a lower risk of death (hazard ratio 0.29, 95% CI: 0.20-0.41). These findings indicate that castration sensitivity is a strong prognostic factor for survival after surgery for spinal metastases from prostate cancer and should be considered in surgical decision-making.

Background: Longitudinal data on weight change, its timing, and the age of obesity onset in relation to cause-specific mortality are limited.

Methods: From ODDS, a nationwide pooled cohort study in Sweden, we included 258,269 men and 361,784 women with at least three weight assessments between ages 17 and 60, collected in 1963–2015. We applied linear mixed-effects models to estimate weight trajectories, age of obesity onset, and age-specific weight changes between ages 17 and 60. Outcomes were all-cause and cause-specific mortality, assessed from 5 years after the last weight assessment until death, emigration, or 31 December 2020. Associations with mortality were calculated using multivariable Cox regression models.

Findings: Over a median follow-up of 23.3 years in men and 11.7 years in women, 86,673 men and 29,076 women died. The median weight change between ages 17 and 60 was 0.42 kg/year in both sexes. A steep weight gain trajectory over this period, early obesity onset, and high weight gain between ages 17 and 29 were associated with higher all-cause mortality and with 13 of 23 specific causes of death investigated in men and 12 of 19 in women. Affected causes included cardiovascular diseases (including most subtypes), cancer (including specific types), type 2 diabetes, and digestive and genitourinary diseases. Hazard ratios (95% confidence intervals) of all-cause mortality associated with obesity onset at ages 17–29 vs. never by age 60 were 1.69 (1.60–1.79) in men and 1.71 (1.55–1.88) in women; and per 0.5 kg/year weight change at ages 17–29, 1.18 (1.17–1.19) and 1.16 (1.14–1.18), respectively. Weight gain later in adulthood generally showed weaker associations, except for cancer mortality in women, where the association was similar to that observed with earlier weight gain.

Interpretation: Weight gain in adulthood, especially in young adulthood, and obesity onset before age 30 are strong risk factors for mortality from multiple non-communicable diseases, underscoring the importance of early obesity prevention. Future studies should incorporate richer confounding data and, ideally, measures of changes in central adiposity and muscle mass. 

Background: Obesity assessed at a single time point in adulthood has shown no consistent association with prostate cancer (PCa) incidence but has been positively associated with PCa death. We investigated the association of total and age-specific adult weight trajectories with PCa aggressiveness and death.

Methods: We analyzed data from 258,494 men in Sweden with at least 3 weight observations between ages 17 and 60. Individual weight trajectories were estimated using linear mixed-effects models with natural cubic and linear splines for age, incorporating random intercepts and slopes. These estimates were included in multivariable-adjusted Cox proportional hazards models.

Results: Over a median follow-up of 25 years, 22 055 men were diagnosed with PCa and 4547 died from the disease. Steep weight gain was inversely associated with PCa diagnosed during the PSA testing era (1997 onwards) and via asymptomatic PSA testing, but not with aggressive PCa. Among men with PCa, steep weight gain was associated with increased risk of PCa death (HR quintile 5 vs. 1 = 1.23, 95% CI = 1.08 to 1.40), primarily driven by weight gain between ages 45 and 60 (HR per 1 kg/year = 1.31, 95% CI = 1.10 to 1.57).

Conclusions: The associations observed for incident PCa appear to be influenced by PSA testing uptake; however, the extent to which detection bias contributes remains uncertain. Conversely, late midlife weight gain was associated with an elevated risk of PCa death, underscoring the importance of weight management during this period as a potentially modifiable factor for reducing PCa death.

The European Association of Urology (EAU) 2021 prognostic model for non–muscle-invasive bladder cancer (NMIBC) is based on the World Health Organization (WHO) 1973 and/or WHO 2004/2022 grading systems for patients who did not receive bacillus Calmette-Guérin (BCG) instillations and is widely used to assess the risk of progression. The estimated risk of progression affects the type of adjuvant intravesical instillation (chemotherapy or BCG), with primary radical cystectomy recommended for patients with the highest risk of progression. We applied the EAU 2021 prognostic model in a population-based setting for 3392 patients with primary NMIBC diagnosed in 2013–2014 according to the BladderBaSe 2.0 database. We assessed the model calibration by comparing the 5-yr progression probability observed in our cohort with the predicted progression probability assigned for the risk groups in the original EAU study, and evaluated the discrimination according to Harrell's C index. At 5-yr follow-up, 394 patients had experienced disease progression. The progression probability observed was 4.9% (95% confidence interval [CI] 3.5–6.3%), 8.6% (95% CI 6.9–10%), 25% (95% CI 22–28%), and 23% (95% CI 14–30%) for the low-, intermediate-, high-, and very high-risk groups, respectively. The discrimination at 5 yr was 0.72 (95% CI 0.69–0.78) for the overall cohort and 0.74 (95% CI 0.70–0.80) in the group excluding the 811 patients who received BCG instillations. Showing moderate predictive ability, the EAU 2021 prognostic model has clinical utility in population-based settings despite underestimation of the observed progression risk in the low- and high-risk groups in the current study. Patient summary: We looked at how well a model predicted the risk of progression of non–muscle-invasive bladder cancer using results for a group of Swedish patients. Approximately one in four patients in the high-risk category progress to more advanced disease within 5 yr. Doctors and patients need to consider the probability of progression in the high-risk category when making shared decisions on which treatment is best for an individual patient.

Prostate cancer (PCa) incidence has steadily increased in Sweden, more steeply in the mid-1990s caused by increased opportunistic prostate-specific antigen (PSA) testing. Tallness, normal weight, and non-smoking are associated with more PSA testing, which increases detection of low-risk and localised PCa. We investigated time trends of height, body mass index (BMI), and smoking with PCa risk in 171,889 men in Sweden aged 50–64 years at baseline, who were linked to nationwide cancer registers during follow-up. Cox regression determined the association of these factors assessed before 1980, 1980–1994, and 1995–2004 with PCa risk. During 15 follow-up years, 8,049 men were diagnosed with PCa. The association of height with PCa was weakly positive across all calendar periods. For obesity (BMI ≥30 kg/m2) vs. normal weight (BMI 18.5–24.9 kg/m2) and current vs. never smoking, the associations changed from null before 1980 (HR 1.03, 95% CI 0.86–1.23, and 1.11, 95% CI 0.97–1.27) to negative in 1995–2004 (HR 0.83, 95% CI 0.74–0.93, and 0.86, 95% CI 0.79–0.93; pinteraction between periods = 0.05 and 0.001). In men with clinical characteristics available, height was positively associated with both aggressive and non-aggressive PCa whilst obesity and smoking showed negative associations only with non-aggressive PCa. These findings likely reflect differences in PSA testing by BMI and smoking habits and contribute important knowledge for etiological studies of PCa.

Introduction: 

For the 3-5% of patients diagnosed with urinary bladder cancer presenting with distant metastases, the five-year survival probability remains below 10% (1–3).

Since the late 1980s, platinum-based combination chemotherapy has been the cornerstone of treatment for metastatic urinary bladder cancer (mUBC) (4, 5). For cisplatin-ineligible patients, carboplatin-gemcitabine was established as an alternative in 2011 (6, 7), and is currently used as first-line chemotherapy in approximately half of the patients treated systemically for mUBC (8). However, platinum-based regimens are associated with a high incidence of serious adverse events (5, 7). Consequently, a substantial proportion of patients with mUBC do not receive any systemic chemotherapy (9). Vinflunine was approved in Europe in 2009 as second-line chemotherapy, though with limited clinical benefit (10, 11).

A new era in the systemic treatment of mUBC was marked by the approval of immune checkpoint inhibitors (ICI) 2017 (12, 13). ICIs demonstrated not only an improved overall survival but also a more favorable toxicity profile. Recent population-based studies have reported improved survival among systemically treated patients with mUBC following the introduction of ICI (14).

Given the historically low uptake of systemic therapy in the real-world setting of mUBC, it remains unclear whether the introduction of immune checkpoint inhibitors (ICI) has translated into improved survival at the population level. As the treatment landscape for mUBC continues to evolve rapidly, benchmarking treatment patterns and survival outcomes in real-world populations is essential to guide clinical practice and policy.

We used the Bladder Cancer Data Base Sweden (BladderBase) 2.0 (15) to investigate survival trends among patients diagnosed with synchronous mUBC between 1997 and 2019 across calendar periods defined by the introduction of novel systemic therapies. We hypothesized that survival in the overall mUBC population improved after the introduction of ICI (2017–2019), due to both the availably of a novel treatment option and an increased proportion of patients eligible for systemic treatment due to ICIs favorable toxicity profile.

Background: Collider bias is often considered a potential explanation when the association between obesity and disease diagnosis differs from that with disease outcome, as seen in the “obesity paradox.” For prostate cancer (PCa), in particular localized PCa, an “inverse” obesity paradox has been observed, where body mass index (BMI) is negatively associated with diagnosis (hazard ratio [HR] ~0.9 per 5-kg/m2 increase), but positively associated with PCa-specific death (HR ~ 1.2). However, collider bias in this context remains unexplored.

Methods: We simulated binary disease diagnosis and outcome data, including the typically unmeasured/unknown background variable (U) that could introduce collider bias. We calculated U-unadjusted (biased) and U-adjusted (true) marginal odds ratios (OR) from a case-only analysis, and determined the bias percentage using (Formula presented.). Similar simulations were performed for classical confounding.

Results: Across a broad range of plausible parameter values for the PCa context, collider bias did not distort the OR of BMI on PCa death by more than 4%, equivalent to a ± 0.04 distortion in the OR estimate for continuous BMI. In comparison, classical confounding showed a higher potential for distorting BMI and PCa death associations than collider bias.

Conclusions: Collider bias alone is unlikely to explain the inverse obesity paradox in (localized) PCa, reinforcing some mechanistic evidence that the observed positive relationship between BMI and PCa death is real, and not a statistical artifact. This finding emphasizes the importance of exploring alternative mechanisms beyond collider bias to better understand the underlying factors driving this paradox.

Background: General adiposity, assessed by body mass index (BMI), is a well-established cancer risk factor. This study compared waist circumference (WC), a measure of abdominal adiposity, with BMI as a risk factor for obesity-related cancers, and assessed whether WC provides additional information beyond BMI.

Methods: We analyzed data from 339 190 individuals in a pooled Swedish cohort with baseline BMI and WC assessments from 1981 to 2019 (61% objectively measured, mean age 51.4 years). Cancer diagnoses were obtained from the Swedish Cancer Register. Hazard ratios (HRs) for WC and BMI were calculated using multivariable-adjusted Cox regression. To account for WC's greater variability, we corrected HRs using regression dilution ratios. To assess WC's additional contribution beyond BMI, we analyzed WC residuals in multivariable, BMI-adjusted models.

Results: During a median follow-up of 13.9 years (interquartile range: 8.0-22.5), 18 185 IARC-established obesity-related cancers were recorded. In men, a 1-standard deviation (SD) increase in WC was associated with a 25% higher risk of obesity-related cancers (HR1-SD = 1.25, 95% CI = 1.21 to 1.30), compared to a 19% increase for BMI (HR1-SD = 1.19, 95% CI = 1.15 to 1.23, P = 0.014 for heterogeneity). Among women, associations were weaker and similar for both WC (HR1-SD = 1.13, 95% CI = 1.11 to 1.16) and BMI (HR1-SD = 1.13, 95% CI = 1.11 to 1.15, P = 0.357 for heterogeneity). Waist circumference residuals were more strongly associated with obesity-related cancer risk in men (HR1-SD = 1.09, 95% CI = 1.06 to 1.12) than in women (HR1-SD = 1.03, 95% CI = 1.02 to 1.05). Including an additional 6893 potential obesity-related cancers yielded similar patterns of associations.

Conclusion(s): Waist circumference is a stronger risk factor than BMI for obesity-related cancer in men, conveying additional risk information, whereas this is less evident in women.