Breast cancer recurrence in relation to mode of detection: implications on personalized surveillance.

PURPOSE: The effectiveness of current follow-up guidelines after breast cancer treatment is uncertain. Tailored surveillance based on patient age and tumor characteristics may be more adequate. This study aimed to analyze the frequency of ipsilateral locoregional recurrences (LR) and second primary breast cancers (SP) detected outside of scheduled surveillance and to analyze risk factors associated with these events. METHODS: Patients with surgically treated early-stage breast cancer from the Malmö Diet and Cancer Study (MDCS), 1991-2014 (n = 1080), and the Västernorrland region, 2009-2018 (n = 1648), were included. Clinical and pathological information on the primary tumor and recurrences was retrieved from medical records. The mode of recurrence detection was defined as detection within (planned) or outside (symptomatic) of scheduled surveillance. RESULTS: The median follow-up was 6.5 years. Overall, 461 patients experienced a recurrence. The most common initial event was distant metastasis (47%), followed by locoregional recurrence (LR) (22%) and second primary (SP) (18%). 56% of LR and 28% of SP were identified outside of scheduled surveillance. Logistic regression analysis revealed that younger age (under 50 years) (OR 2.57, 95% CI 1.04-6.88), lymph node-positive breast cancer (OR 2.10, 95% CI 1.03-4.39) and breast cancer of the HER2 positive subtype (OR 5.24, 95% CI 1.40-25.90) were correlated with higher odds of detecting a recurrence outside of planned surveillance. CONCLUSION: Most recurrent events were detected outside of scheduled surveillance, particularly for locoregional recurrences. Risk-based surveillance, which takes into account patient and tumor characteristics, might be more suitable for specific patient subsets.

Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

Impact of era of diagnosis on cause-specific late mortality among 77 423 five-year European survivors of childhood and adolescent cancer: The PanCareSurFup consortium.

Late mortality of European 5-year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause-specific mortality among older European survivors. PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries from 77 423 five-year survivors of cancer diagnosed before age 21 between 1940 and 2008 followed for an average age of 21 years and a total of 1.27 million person-years to determine their risk of death using cumulative mortality, standardized mortality ratios (SMR), absolute excess risks (AER), and multivariable proportional hazards regression analyses. At the end of follow-up 9166 survivors (11.8%) had died compared to 927 expected (SMR 9.89, 95% confidence interval [95% CI] 9.69-10.09), AER 6.47 per 1000 person-years, (95% CI 6.32-6.62). At 60 to 68 years of attained age all-cause mortality was still higher than expected (SMR = 2.41, 95% CI 1.90-3.02). Overall cumulative mortality at 25 years from diagnosis dropped from 18.4% (95% CI 16.5-20.4) to 7.3% (95% CI 6.7-8.0) over the observation period. Compared to the diagnosis period 1960 to 1969, the mortality hazard ratio declined for first neoplasms (P for trend <.0001) and for infections (P < .0001); declines in relative mortality from second neoplasms and cardiovascular causes were less pronounced (P = .1105 and P = .0829, respectively). PanCareSurFup is the largest study with the longest follow-up of late mortality among European childhood and adolescent cancer 5-year survivors, and documents significant mortality declines among European survivors into modern eras. However, continuing excess mortality highlights survivors' long-term care needs.

Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe).

OBJECTIVE: To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis. PATIENTS AND METHODS: Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC. RESULTS: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis. CONCLUSIONS: OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study.

OBJECTIVE: To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of <3 months. PATIENTS AND METHODS: We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at ≥25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually. RESULTS: PSMAV in the highest tertile (≥25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis. CONCLUSIONS: The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

Primary surgery with or without postoperative radiotherapy in early stage squamous cell carcinoma in the anal canal and anal margin.

BACKGROUND: Standard treatment of localized squamous cell carcinoma of the anus (SCCA) is radiotherapy (RT) combined with chemotherapy, that is, chemoradiation (CRT). Primary surgery has a limited role, but is a recommended treatment for small well differentiated SCCA localized in the anal margin, with re-excision or postoperative RT/CRT in case of involved surgical margins. The evidence supporting these strategies is limited. AIM: To study the recurrence patterns and survival outcomes in patients treated with surgery alone compared with surgery followed by postoperative RT/CRT. MATERIAL AND METHODS: From a large Nordic database we identified 93 patients with stage TxT1-2N0M0 SCCA treated with surgery alone (n = 59) or surgery followed by RT/CRT (n = 34). Surgery consisted of local excision in 86 patients and abdominoperineal resection in seven patients, all of them in the surgery alone group. In 38 (41%) of the patients, the tumor was localized merely in the anal margin and in all remaining cases the anal canal was involved. Median RT dose to the tumor bed was 54 (range 46-66) Gy. Adjuvant RT to lymph nodes was given in 75% of the patients. Half of the patients received concomitant chemotherapy, usually 5-fluorouracil and mitomycin C. RESULTS: The locoregional recurrence (LRR) rate was significantly higher after surgery alone compared to surgery followed by adjuvant RT/CRT (36% vs. 9%, p = .006). The 3-year recurrence free survival (RFS) and overall survival (OS) were significantly better in patients who received postoperative RT/CRT than in patients who did not (3-year RFS 84.2% vs. 52.7%, p < .001 and 3-year OS 87.2% vs. 70%, p = .026). CONCLUSIONS: Surgery alone of SCCA was associated with a high LRR rate and poor survival. The addition of postoperative RT/CRT lead to significantly improved locoregional control and survival.

The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: a cohort from 12 European countries.

Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.

Benefits, barriers and opinions on multidisciplinary team meetings: a survey in Swedish cancer care.

BACKGROUND: Case review and discussion at multidisciplinary team meetings (MDTMs) have evolved into standard practice in cancer care with the aim to provide evidence-based treatment recommendations. As a basis for work to optimize the MDTMs, we investigated participants' views on the meeting function, including perceived benefits and barriers. METHODS: In a cross-sectional study design, 244 health professionals from south Sweden rated MDTM meeting structure and function, benefits from these meetings and barriers to reach a treatment recommendation. RESULTS: The top-ranked advantages from MDTMs were support for patient management and competence development. Low ratings applied to monitoring patients for clinical trial inclusion and structured work to improve the MDTM. Nurses and cancer care coordinators did less often than physicians report involvement in the case discussions. Major benefits from MDTM were reported to be more accurate treatment recommendations, multidisciplinary evaluation and adherence to clinical guidelines. Major barriers to a joint treatment recommendation were reported to be need for supplementary investigations and insufficient pathology reports. CONCLUSIONS: Health professionals' report multiple benefits from MDTMs, but also define areas for improvement, e.g. access to complete information and clarified roles for the different health professions. The emerging picture suggests that structures for regular MDTM evaluations and increased focus on patient-related perspectives should be developed and implemented.

Fast-track access to urologic care for patients with macroscopic haematuria is efficient and cost-effective: results from a prospective intervention study.

BACKGROUND: The delay between onset of macroscopic haematuria and diagnosis of bladder cancer is often long. METHODS: We evaluated timely diagnosis and health-care costs for patients with macroscopic haematuria given fast-track access to diagnostics. During a 15-month period, a telephone hotline for fast-track diagnostics was provided in nine Swedish municipalities for patients aged ⩾50 years with macroscopic haematuria. The control group comprised 101 patients diagnosed with bladder cancer in the same catchment area with macroscopic haematuria who underwent regular diagnostic process. RESULTS: In all 275 patients who called 'the Red Phone' hotline were investigated, and 47 of them (17%) were diagnosed with cancer and 36 of those had bladder cancer. Median time from patient-reported haematuria to diagnosis was 29 (interquartile range (IQR) 14-104) days and 50 (IQR 27-165) days in the intervention and the control group, respectively (P=0.03). The median health-care costs were lower in the intervention group (655 (IQR 655-655) EUR) than in the control group (767 (IQR 490-1096) EUR) (P=0.002). CONCLUSIONS: Direct access to urologic expertise and fast-track diagnostics is motivated for patients with macroscopic haematuria to reduce diagnostic intervals and lower health-care expenditures.

A randomized comparison between league tables and funnel plots to inform health care decision-making.

OBJECTIVE: Comparison of provider performance is commonly used to inform health care decision-making. Little attention has been paid to how data presentations influence decisions. This study analyzes differences in suggested actions by decision-makers informed by league tables or funnel plots. DESIGN: Decision-makers were invited to a survey and randomized to compare hospital performance using either league tables or funnel plots for four different measures within the area of cancer care. For each measure, decision-makers were asked to suggest actions towards 12-16 hospitals (no action, ask for more information, intervene) and provide feedback related to whether the information provided had been useful. SETTING: Swedish health care. PARTICIPANTS: Two hundred and twenty-one decision-makers at administrative and clinical levels. INTERVENTION: Data presentations in the form of league tables or funnel plots. MAIN OUTCOME MEASURES: Number of actions suggested by participants. Proportion of appropriate actions. RESULTS: For all four measures, decision-makers tended to suggest more actions based on the information provided in league tables compared to funnel plots (44% vs. 21%, P < 0.001). Actions were on average more appropriate for funnel plots. However, when using funnel plots, decision-makers more often missed to react even when appropriate. CONCLUSIONS: The form of data presentation had an influence on decision-making. With league tables, decision-makers tended to suggest more actions compared to funnel plots. A difference in sensitivity and specificity conditioned by the form of presentation could also be identified, with different implications depending on the purpose of comparisons. Explanations and visualization aids are needed to support appropriate actions.

The impact of age on survival of diffuse large B-cell lymphoma - a population-based study.

BACKGROUND: For Diffuse large B-cell lymphoma (DLBCL), the International Prognostic Index is the major tool for prognostication and considers an age above 60 years as a risk factor. However, there are several indications that increasing age is associated with more biological complexity, resulting in differences in DLBCL biology depending on age. METHODS: We conducted a registry-based retrospective cohort study of all Swedish DLBCL patients diagnosed 2000-2013, to evaluate the importance of age at diagnosis for survival of DLBCL patients. RESULTS: In total, 7166 patients were included for further analysis. Survival declined for every 10-year age group and every age group above the age of 39 had a statistically decreased survival compared to the reference group of 20-29 years. In an analysis of relative survival, and in a multifactorial model adjusted for stage, ECOG performance status, serum lactate dehydrogenase and involvement of extranodal sites, each age group above age 39 had a significantly higher risk ratio (p=0.01) compared to the reference group. CONCLUSION: This is one of the largest population-based studies of DLBCL published to date. In this study, age persisted as a significant adverse risk factor for patients as young as 40 years, even after adjustment for other risk factors.

Acute myeloid leukemia in the real world: why population-based registries are needed.

Population-based registries may provide data complementary to that from basic science and clinical intervention studies, all of which are essential for establishing recommendations for the management of patients in the real world. The same quality criteria apply for the evidence-based label, and both high representation and good data quality are crucial in registry studies. Registries with high coverage of the target population reduce the impact of selection on outcome and the subsequent problem with extrapolating data to nonstudied populations. Thus, data useful for clinical decision in situations not well covered by clinical studies can be provided. The potential clinical impact of data from population-based studies is exemplified with analyses from the Swedish Acute Leukemia Registry containing more than 3300 acute myeloid leukemia (AML) patients diagnosed between 1997 and 2006 with a median follow-up of 6.2 years on (1) the role of intensive combination chemotherapy for older patients with AML, (2) the impact of allogeneic stem cell transplantation on survival of younger patients with AML, and (3) the continuing problem with early deaths in acute promyelocytic leukemia. We also present the first Web-based dynamic graph showing the complex interaction between age, performance status, the proportion of patients given intensive treatment, early death rate, complete remission rate, use of allogeneic transplants, and overall survival in AML (non-AML).

[Radical cystectomy for bladder cancer is a complex procedure]. / Cystektomi för blåscancer ­ har utfallet förbättrats?

Radical cystectomy (RC) for bladder cancer is a complex procedure with an inherent risk of complications and even postoperative mortality. Historically, RC was performed in 44 hospitals in Sweden, which gradually decreased over time, and since a formal regional centralisation of these operations in 2017, cystectomy care is currently provided by nine hospitals. In the Swedish national urinary bladder cancer register (SNRUBC), complications after RC has been registered with high coverage since 2012, with data presented in an interactive online data resource (RODRET). Over time, an increased median age and proportion of patients with significant comorbidity (ASA 3 or 4) were observed between 2012 and 2022. A simultaneous decrease in 90-day mortality from 7 percent to 2 percent was noted, as well as a decreased need for reoperations within 90 days of RC from 11 percent to 7 percent. It is likely that the regionalization of the cystectomy care in Sweden has contributed to these improved outcomes.

Cystectomy for bladder cancer in Sweden - short-term outcomes after centralization.

OBJECTIVE: Radical cystectomy (RC) for bladder cancer is associated with an inherent risk of complications and even postoperative mortality. The number of hospitals performing RC has decreased in Sweden over time, and since a formal regional centralization in 2017 cystectomy care is currently provided by nine hospitals. MATERIAL AND METHODS: In the Swedish National Urinary Bladder Cancer Register (SNRUBC) 90-day complications after RC have been registered with high coverage since 2012. Descriptive data and short-term outcomes were compared in relation to centralization of the cystectomy care by stratifying data before (2012-2016) and after (2017-2023). RESULTS: Out of all 4,638 cystectomies, 2,738 (59%) were performed after the centralization in 2017 and onwards. The median age at RC increased from 71 (Inter Quartile Range [IQR] 65-76) to 73 (IQR 67-77) years, and the proportion of patients with comorbidity (American Society of Anesthesiologists [ASA] 3 or 4) increased from 32% to 37% after the centralization (p < 0.001). The number of patients suffering from high-grade complications within 90 days of surgery corresponding to Clavien grade three were 345 (18%) and 407 (15%), and corresponding to Clavien grade four 61 (3%) and 64 (2%) before and after centralization, respectively. Reoperations within 90 days of RC decreased from 234/1,900 (12%) to 208/2,738 (8%) (p < 0.001), and 90-day mortality decreased from 84/1,900 (4%) to 85/2,738 (3%) (p = 0.023) before and after centralization, respectively. CONCLUSION: After the centralization of the cystectomy-care in Sweden, older patients and individuals with more extensive comorbidity were offered RC whereas 90-day mortality and the proportion of patients subjected to reoperations within 90 days of surgery decreased without increasing waiting times.

Diagnostic pathways and treatment strategies in upper tract urothelial carcinoma in Sweden between 2015 and 2021: a population-based survey.

OBJECTIVE: To report national data on diagnostics and treatment of upper tract urothelial carcinoma (UTUC) from the Swedish National Registry of Urinary Bladder Cancer (SNRUBC). PATIENTS AND METHODS: Data from 2015 to 2021 were retrieved, and descriptive analyses were performed regarding incidence, diagnostic modalities, preoperative tumor staging, quality indicators for treatment including the use of standardized care pathways (SCP) and multidisciplinary tumor boards (MDTB). Time trends were explored for the study period. RESULTS: Registrations included 1,213 patients with renal pelvic cancer and 911 patients with ureteric cancer with a median age of 74 (interquartile range [IQR] 70-77) and 75 (IQR 71-78) years, respectively. Incidence rates of UTUC were stable, as were proportions of curative treatment intent. Median number of days from referral to treatment was 76 (IQR 57-99) and 90 (IQR 72-118) days, respectively, for tumors of the renal pelvis and ureter, which remained unchanged after introduction of SCP in 2016. Noticeable trends included stable use of kidney-sparing surgery and increased use of MDTB. For radical nephroureterectomy (RNU), robot-assisted technique usage increased even for non-organ-confined tumors (cT3-4) and in one out of three patients undergoing RNU a bladder cuff excision was not registered. CONCLUSIONS: The population-based SNRUBC with high coverage contributes to the knowledge about UTUC with granular and generalizable data. The present study reveals a high proportion of patients not subjected to curatively intended treatment and suggests unmet needs to shorten lead times to treatment and use of bladder cuff excision when performing radical surgery for UTUC in Sweden.

Treatment Related to Urinary Tract Infections Is Associated with Delayed Diagnosis of Urinary Bladder Cancer: A Nationwide Population-based Study.

BACKGROUND AND OBJECTIVE: It has been suggested that urinary tract infections (UTIs) are associated with delayed diagnosis of bladder cancer (BC). Our aim was to investigate prediagnostic treatments related to UTI and the relation to BC diagnostic delay, reflected by advanced disease at diagnosis. METHODS: We used data from the BladderBaSe 2.0 with data of treatments related to UTI up to 3 yr before BC diagnosis (2008-2019) for BC patients in comparison to a matched reference population. We investigated the association between UTI treatments and more advanced disease at diagnosis in the BC cohort. We used generalized ordered logistic regression to calculate odds ratios (ORs) for more advanced disease as an ordered outcome: non-muscle-invasive BC (NMIBC), muscle-invasive BC (MIBC), and metastatic BC (MBC). KEY FINDINGS AND LIMITATIONS: The study population included 29 921 BC patients and 149 467 matched reference subjects. The proportions of individuals receiving UTI treatment were higher in the patient groups than in the corresponding reference groups, with the greatest differences observed for the MIBC and MBC subgroups. The OR for the risk of more advanced disease (MIBC or MBC) with at least one UTI treatment versus none was 1.28 (95% confidence interval [CI] 1.19-1.37) for men and 1.42 (95 % CI 1.27-1.58) for women. The association to risk of more advanced disease increased with the number of UTI treatments for both sexes. CONCLUSIONS AND CLINICAL IMPLICATIONS: Further studies on the effects of treatments related to UTI in combination with other factors are needed to identify reasons for possible delays in the BC diagnostic pathway. PATIENT SUMMARY: We found that for patients with bladder cancer, previous antibiotic treatment for a urinary tract infection was linked to more advanced disease at diagnosis. Further studies are needed to identify reasons for possible delays in the diagnosis of bladder cancer.

The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non-muscle-invasive Bladder Cancer.

Grade is an important determinant of progression in non-muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers.

The association between BCG treatment in patients with bladder cancer and subsequent risk of developing Alzheimer and other dementia.-A Swedish nationwide cohort study from 1997 to 2019.

BACKGROUND: Alzheimer's disease (AD) affects 50 million people worldwide. The immune system plays a major role in the pathogenesis of AD. Several retrospective analyses have reported a decreased risk of AD and other dementias in bladder cancer patients treated with immunotherapy in the form of Bacillus Calmette-Guerin (BCG) bladder instillations. We tested this hypothesis in a Swedish population-based prospective cohort of patients with non-muscle invasive bladder cancer (NMIBC). METHODS AND FINDINGS: We utilized the BladderBaSe 2.0 database, which contains tumor-specific, health-related, and socio-demographic information for patients diagnosed with NMIBC between 1997 and 2019. The database also includes a matched comparison cohort sampled from the general population, consisting of individuals free from urinary tract cancer at the time of the index case's diagnosis. Five controls were randomly selected for each index case without replacement on the date of the index case's diagnosis. Our inclusion criteria identified participants diagnosed with NMIBC who had received BCG as primary treatment, along with their corresponding comparison cohort. We excluded those diagnosed with dementia before or within 6 months of NMIBC diagnosis. To compare the NMIBC cohort with their matched comparison cohort, we used a stratified Cox model, treating each case with its controls as a stratum. We identified 38,934 patients in the NMIBC cohort, with 6,496 receiving BCG after primary diagnosis (cases). AD/dementia was diagnosed during follow-up in 6.1% of cases and 7.4% of controls. Cases had a slightly lower risk of dementia than controls, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI] 0.780-0.991), and a HR of 0.89 (CI 0.703-1.119) for AD. Subgroup analysis for dementia showed that age over 75 years had an HR of 0.73 (CI 0.616-0.863), and female gender had an HR of 0.73 (CI 0.552-0.971). The associations were similar for AD specifically, but not statistically significant. Similar to previous studies, we analyzed bladder cancer patients treated with and without BCG therapy. Multivariate Cox analysis indicated that those treated with BCG had a lower risk of dementia (HR 0.81, 95% CI 0.71-0.92), and an HR of 0.98 (95% CI 0.75-1.27) for AD specifically. High age was a significant risk modifier; the HR was 3.8 (CI 3.44-4.11) for dementia and 3.1 (CI 2.59-3.73) for AD. Even patients not receiving BCG had a significantly lower risk for AD than controls (HR 0.86, CI 0.77-0.96). CONCLUSIONS: This study observed a marginally decreased risk of developing AD/dementia associated with earlier intravesical BCG treatment in NMIBC patients. This small benefit was most pronounced in those with high age and female gender. The disparity from previous highly positive studies underscores the importance of using an appropriate control cohort.

FDG-PET/CT for lymph node staging prior to radical cystectomy.

BACKGROUND: 18F-Fluorodeoxyglucose positron emission combined with computed tomography (FDG-PET/CT) has been proposed to improve preoperative staging in patients with bladder cancer subjected to radical cystectomy (RC). OBJECTIVE: Our aim was to assess the accuracy of FDG-PET/CT for lymph node staging ascertained at the multidisciplinary tumour board compared to lymph node status in the surgical lymphadenectomy specimen obtained at RC, and to explore potential factors associated with false-positive FDG-PET/CT results. DESIGN, SETTING AND PARTICIPANTS: Consecutive patients with bladder cancer undergoing RC with extended lymph node dissection between 2011 and 2019 without preoperative chemotherapy in a tertial referral cystectomy unit were included in the study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Potential factors investigated for association with false-positive FDG-PET/CT were; bacteriuria within four weeks prior to FDG-PET/CT, Bacillus Calmette-Guerin (BCG) treatment within 12 months prior to FDG-PET/CT and transurethral resection of bladder tumour (TURB) within four weeks prior to FDG-PET/CT. RESULTS: Among 157 patients included for analysis, 44 (28%) were clinically node positive according to FDG-PET/CT. The sensitivity and specificity for detection of lymph node metastasis were 50% and 84%, respectively, and the corresponding positive predictive and negative predictive values were 61% and 76%. Positive and negative likelihood ratios were 3.0 and 0.6, respectively. No association was found between bacteriuria, previous BCG treatment or TURB within 28 days and false-positive FDG-PET/CT results. CONCLUSIONS: Preoperative FDG-PET/CT prior to RC had a clinically meaningful high specificity (84%) but lower sensitivity (50%) for detection of lymph node metastases compared to lymph node status in an extended pelvic lymphadenectomy template. We could not identify any factors associated with false-positive FDG-PET/CT outcomes.