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Objective: To overview and summarise the Swedish National Guidelines on Urothelial Carcinoma 2024.

Methods: A narrative review of the updated guidelines was performed, highlighting new treatment recommendations for advanced and metastasized disease.

Results: Compared to the previous guideline version, the current update includes recommendations for standardised radiological reporting when urothelial carcinomas are detected at CT-urography (CTU), to early identify locally advanced patients and accelerate the care pathway for these patients. The Swedish guidelines apply a more structured and liberal recommendation for the use of18F-fluorodeoxyglucose-positron emission tomography/computed tomography in patients with locally advanced urothelial carcinomas compared to the EAU-guidelines and recommend such examinations prior to transurethral resection. Improved outcomes for radical cystectomy in Sweden after centralised cystectomy care have led to a recommendation for performing more than six nephroureterectomies (NUs) per year for upper tract urothelial carcinomas (UTUC)-based associations with decreased use of invasive diagnostic modalities and better survival outcomes. Additionally, updated recommendations regarding adjuvant systemic therapies for muscle-invasive disease have been included. Whilst awaiting national regulatory approval for enfortumab vedotin/pembrolizumab, the present guideline version aligns with EAU-guidelines by endorsing cisplatin-gemcitabine-nivolumab as a new first-line treatment option in cisplatin-fit patients with unresectable or metastatic urothelial carcinoma.

Conclusions: The current version of the Swedish national guidelines on urothelial carcinoma introduces standardised reporting at CTU to facilitate early identification of advanced disease, includes recommendations for centralisation of NU for UTUC and updated recommendations for adjuvant systemic treatment of muscle-invasive disease and endorses cisplatin-gemcitabine-nivolumab as a new first-line treatment option for non-resectable locally advanced and metastatic disease.

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.

BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.

MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.

RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.

INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.

Background: Should early response imaging predict tumor response to therapy, personalized treatment adaptations could be feasible to improve outcome or reduce the risk of adverse events. This prospective single-center observational study on 2-fluorine-18-fluoro-deoxy-glucose (2-[18F]FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) features aims to investigate the association between semantic 2-[18F]FDG-PET/MRI imaging parameters and outcome prediction in uterine cervical squamous cell carcinoma (CSCC) treated with radiotherapy.

Results: Eleven study participants with previously untreated CSCC were examined with 2-[18F]FDG-PET/MRI at baseline and approximately one week after start of curative radiotherapy. All study participants had at least 24 months clinical follow-up. Two patients relapsed during the follow-up period. Reduced tumor size according to visual assessment was present in 9/11 participants (median change in sum of largest diameters (SLD) − 10.4%; range − 2.5 to − 24.6%). The size reduction was less pronounced in the relapse group compared to the no relapse group, with median change in SLD − 4.9%, versus − 10.4%. None of the reductions qualified as significantly reduced or increased in size according to RECIST 1.1., hence all participants were at this stage classified as non-responders/stable disease. Median baseline functional tumor volume (FTV) for the relapse group was 126 cm3, while for the no relapse group 9.3 cm3. Median delta FTV in the relapse group was 50.7 cm3, representing an actual increase in metabolically active volume, while median delta FTV in the no relapse group was − 2.0 cm3. Median delta apparent diffusion coefficient (ADC) was lower in the relapse group versus the no relapse group (− 3.5 mm2/s vs. 71 mm2/s).

Conclusions: Early response assessment with 2-[18F]FDG-PET/MRI identified potentially predictive functional imaging biomarkers for prediction of radiotherapy outcome in CSCC, that could not be recognized with tumor measurements according to RECIST 1.1. These biomarkers (delta FTV and delta ADC) should be further evaluated.

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.

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.

Background and purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions.

Material and methods: The study participants were examined with [68Ga]PSMA-PET/mpMRI prior to radical prostatectomy. Four radiation oncologists delineated GTVs in 15 study participants, on four different image types; T2-weighted (T2w), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and PSMA-PET scans separately. The simultaneous truth and performance level estimation (STAPLE) algorithm was used to generate combined GTVs. GTVs were subsequently compared to histopathology. We analysed how Dice similarity coefficient (DSC) and lesion coverage are affected by using single versus multiple image types as well as by adding a clinical target volume (CTV) margin.

Results: Median DSC (STAPLE) for different GTVs varied between 0.33 and 0.52. GTVPSMA-PET/mpMRI generated the highest median lesion coverage at 0.66. Combining different image types achieved similar lesion coverage as adding a CTV margin to contours from a single image type, while reducing non-malignant tissue inclusion within the target volume.

Conclusion: The combined use of mpMRI or PSMA-PET/mpMRI shows promise, achieving higher DSC and lesion coverage while minimizing non-malignant tissue inclusion, in comparison to the use of a single image type with an added CTV margin.

Manual segmentations are considered the gold standard for ground truth in machine learning applications. Such tasks are tedious and time-consuming, albeit necessary to train reliable models. In this work, we present a dataset with expert segmentations of the prostatic zones and urethra for 200 randomly selected patients from the PROSTATEx dataset. Notably, independent duplicate segmentations were performed for 40 patients, providing inter-reader variability data. This results in a total of 240 segmentations. This dataset can be used to train machine learning models or serve as an external test set for evaluating models trained on private data, thereby addressing a current gap in the field. The delineated structures and terminology adhere to the latest Prostate Imaging Reporting and Data Systems v2.1 guidelines, ensuring consistency.

Introduction: Real-life data on vismodegib in advanced basal cell carcinoma (aBCC) are limited. Optimal treatment duration is left to the discretion of the physician.

Objectives: To assess the effectiveness, safety and treatment pattern for vismodegib in aBCC in clinical practice.

Methods: In this multicenter, non-interventional, prospective study, 49 Swedish patients planned for vismodegib treatment were included. The treatment pattern observed was treatment until remission, allowing unlimited discontinuations/pauses.

Results: The majority of patients (93.8%), discontinued at least once during the study. Compared to earlier studies there was a decrease of more than 2 months with actual drug intake, reducing the patients burden and costs, at the same time as a high number of responses were seen (87.8%). Median progression-free-survival was 16.7 months, and 90% of the patients were alive at 13.3 months. Ten patients were re-challenged with vismodegib at recurrence or progression, resulting in five partial remissions and three complete remissions.

Conclusions: Clinical response rates with vismodegib for aBCC were comparable to those of similar trials despite a shorter and more intermittent treatment duration. The majority of re-challenges lead to partial or complete remissions.

Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [⁶⁸Ga]PSMA-11-PET (PSMA)-PET, [¹¹C] Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility.

Methods: During 2016–2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement.

Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance (P = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET.

Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach.