| 1. |
- Ahlberg, Mats Steinholtz, et al.
(författare)
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Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes
- 2023
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 52, s. 166-173
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Tidskriftsartikel (refereegranskat)abstract
- Background: Regional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies.Objective: To examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death.Design, setting, and participants: A Swedish population-based cohort study was con-ducted including men in the National Prostate Cancer Register in Sweden with low -risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019.Intervention: Regional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysis:Probabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed.Results and limitations: We included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0-7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI -0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting.Conclusions:A regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment.
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| 2. |
- Almdalal, T., et al.
(författare)
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Clinical T1a Renal Cell Carcinoma, Not Always a Harmless Disease-A National Register Study
- 2022
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 39, s. 22-28
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Tidskriftsartikel (refereegranskat)abstract
- Background: T1a renal cell carcinoma (RCC) is typically considered a curable dis-ease, irrespective of the choice of local treatment modality.& nbsp;Objective: To identify factors associated with the risk of local and distant recur-rence, and overall survival (OS) in patients with primary nonmetastatic clinical T1a RCC.& nbsp;Design, setting, and participants: A population-based nationwide register study of all 1935 patients with cT1a RCC, diagnosed during 2005-2012, identified through The National Swedish Kidney Cancer Register, was conducted.& nbsp;Outcome measurements and statistical analysis: Outcome variables were recur-rence (local or distant) and OS. Possible explanatory variables included tumor size, RCC type, T stage, surgical technique, age, and gender. Associations with disease recurrence and OS were evaluated by multivariable regression and Cox multivari-ate analyses, respectively.& nbsp;& nbsp;Results and limitations: Among 1935 patients, 938 were treated with radical nephrectomy, 738 with partial nephrectomy, and 169 with ablative treatments, while 90 patients had no surgery. Seventy-eight (4%) patients were upstaged to pT3. Local or metastatic recurrences occurred in 145 (7.5%) patients, significantly more often after ablation (17.8%). The risk of recurrence was associated with tumor size, upstaging, and ablation. Larger tumor size, disease recurrence, and older age adversely affected OS, whereas partial nephrectomy and chromophobe RCC (chRCC) were associated with improved survival. Limitations include register design and a lack of comorbidity or performance status data.& nbsp;Conclusions: Upstaging and recurrence occurred, respectively, in 4.0% and 7.5% of patients with nonmetastatic RCCs <= 4 cm. Tumor size upstaging and ablation were associated with the risk for recurrence, while tumor size and recurrence were associated with decreased OS. Patients with chRCC and partial nephrectomy had prolonged OS in a real-world setting.& nbsp;Patient summary: We studied factors that may influence the risk of disease recurrence and overall survival, in a large nationwide patient cohort having non metastatic renal cell carcinoma < 4 cm. Tumor size, tumor type, and treatment were associated with the risk of recurrence and overall death. Partial nephrectomy prolonged overall survival. (C)2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
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| 3. |
- Axén, Elin, et al.
(författare)
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Degree of Preservation of Neurovascular Bundles in Radical Prostatectomy and Recurrence of Prostate Cancer
- 2021
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 30, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reports on possible benefits for continence with nerve-sparing (NS) radical prostatectomy have expanded the indications beyond preservation of erectile function. It is unclear whether NS surgery affects oncological outcomes. Objective: To determine whether the degree of NS during radical prostatectomy influences oncological outcomes. Design, setting, and participants: Of 4003 patients enrolled in a prospective, controlled trial comparing open and robotic radical prostatectomy during 2008–2011, we evaluated 2401 patients who received robotic radical prostatectomy at seven Swedish centres. Patients were followed for 8 yr. Outcome measurements and statistical analysis: Data for recurrence and positive surgical margin status were assessed using validated patient questionnaires, patient interviews, and clinical record forms before and at 3, 12, and 24 mo and 6 and 8 yr after surgery. Cox and logistic regressions were used to model the effect on recurrence and positive surgical margins (PSM), respectively. Results and limitations: A total of 481 men had PSM and 467 experienced recurrence during follow-up. Median follow-up for men without recurrence was 6.6 yr. There were no statistically significant differences in recurrence rate between degrees of NS. The PSM rate was significantly higher with a higher degree of NS: interfascial NS, odds ratio (OR) 2.32 (95% confidence interval [CI] 1.69–3.16); intrafascial NS, OR 3.23 (95% CI 2.17–4.80). Recurrence rates were higher for patients with pT2 disease and PSM (hazard ratio [HR] 3.32, 95% CI 2.43–4.53) than for patients with pT3 disease without PSM (HR 2.08, 95% CI 1.66–2.62). The lack of central review of pathological specimens is a limitation. Conclusions: A higher degree of NS significantly increased the risk of PSM but did not significantly increase the risk of cancer recurrence. Combined with the known functional benefits of NS surgery, these results underscore the need to identify an individualised balance. Patient summary: In this report we looked at the effect of a nerve-sparing approach during removal of the prostate on cancer outcomes for patients having robot-assisted surgery at seven Swedish hospitals. We found that a high degree of nerve-sparing increased the rate of cancer positivity at the margins of surgical specimens and that positive surgical margins increased the risk of recurrence of prostate cancer. © 2021 The Authors
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| 4. |
- Bergengren, Oskar, et al.
(författare)
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Satisfaction with Nurse-led Follow-up in Prostate Cancer Patients-A Nationwide Population-based Study
- 2022
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 38, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Satisfaction with nurse-led follow-up among men with prostate can-cer is high. However, it is unclear whether all men are satisfied or whether there are men who would benefit from being followed by a urologist or a nurse.Objective: To investigate the follow-up distribution between urologists and nurses, and whether the high self-reported satisfaction with nurse-led follow-up is inde-pendent of other factors such as age or comorbidity.Design, setting, and participants: All Swedish men, <= 70 yr of age, with a low-risk prostate cancer diagnosis in 2008, answered a questionnaire 7 yr after diagnosis. The extensive questionnaire included a question on satisfaction with care, answered on a seven-point scale. Participants were divided based on whether they were followed up by a nurse, a urologist, or both.Outcome measurements and statistical analysis: Factors that could influence the level of satisfaction were identified as age, edu-cation, comorbidity, treatment, disease progression, urinary bother, level of infor-mation, and participation in treatment decision. Likelihood ratio tests from ordinal regression were used to test the null hypothesis of similar satisfaction between groups.Results and limitations: Out of 1288 men, 1137 (88%) answered both the question on who performed the follow-up and the question regarding satisfaction. In all, 350 men reported that they were followed up by nurses (31%), 598 (52%) by urologists, and 189 (17%) by both. No differences in satisfaction where seen between the groups. Approximately 50% were satisfied completely, regardless of who performed the follow-up. Results were not affected by age, educational level, comorbidity, treatment, disease progression, urinary bother, information, or participation in treatment decision. Limitations include the nonrandomized, retrospective design and a potential recall bias.Conclusions: Satisfaction with nurse-led follow-up is high, regardless of factors such as age, level of education, comorbidity, and treatment.Patient summary: Men with prostate cancer can be offered nurse-led follow-up on a regular basis and still maintain their satisfaction with health care.
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| 5. |
- Beyer, Katharina, et al.
(författare)
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A Systematic Review of Heterogeneity in Outcome Definition and Reporting in Localised Renal Cancer
- 2023
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 48, s. 1-11
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Forskningsöversikt (refereegranskat)abstract
- Context: Outcomes in renal cell carcinoma (RCC) are reported inconsistently, with variability in definitions and measurement. Hence, it is difficult to compare intervention effectiveness and synthesise outcomes for systematic reviews and to create clinical practice guidelines. This uncertainty in the evidence makes it difficult to guide patient-clinician decision-making. One solution is a core outcome set (COS): an agreed minimum set of outcomes. Objective: To describe outcome reporting, definitions, and measurement heterogeneity as the first stage in co-creating a COS for localised renal cancer. Evidence acquisition: We systematically reviewed outcome reporting heterogeneity in effectiveness trials and observational studies in localised RCC. In total, 2822 studies (randomised controlled trials, cohort studies, case-control studies, systematic reviews) up to June 2020 meeting our inclusion criteria were identified. Abstracts and full texts were screened independently by two reviewers; in cases of disagreement, a third reviewer arbitrated. Data extractions were double-checked. Evidence synthesis: We included 149 studies and found that there was inconsistency in which outcomes were reported across studies and variability in the definitions used for outcomes that were conceptually the same. We structured our analysis using the outcome classification taxonomy proposed by Dodd et al. Outcomes linked to adverse events (eg, bleeding, outcomes linked to surgery) and renal injury outcomes (reduced renal function) were reported most commonly. Outcomes related to deaths from any cause and from cancer were reported in 44% and 25% of studies, respectively, although the time point for measurement and the analysis methods were inconsistent. Outcomes linked to life impact (eg, global quality of life) were reported least often. Clinician-reported outcomes are more frequently reported than patient-reported outcomes in the renal cancer literature. Conclusions: This systematic review underscores the heterogeneity of outcome reporting, definitions, and measurement in research on localised renal cancer. It catalogues the variety of outcomes and serves as a first step towards the development of a COS for localised renal cancer. Patient summary: We reviewed studies on localised kidney cancer and found that multiple terms and definitions have been used to describe outcomes. These are not defined consistently, and often not defined at all. Our review is the first phase in developing a core outcome set to allow better comparisons of studies to improve medical care.
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| 6. |
- Bjartell, Anders, et al.
(författare)
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Real-world Treatment Sequencing in Patients with Metastatic Castration-resistant Prostate Cancer: Results from the Prospective, International, Observational Prostate Cancer Registry
- 2022
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 45, s. 12-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer has a multifaceted treatment pattern. Evidence is lacking for optimal treatment sequences for metastatic castration-resistant prostate cancer (mCRPC).Objective: To increase the understanding of real-world treatment pathways and outcomes in patients with mCRPC.Design, setting, and participants: A prospective, noninterventional, real-world analysis of 3003 patients with mCRPC in the Prostate Cancer Registry (PCR; NCT02236637) from June 14, 2013 to July 9, 2018 was conducted.Intervention: Patients received first- and second-line hormonal treatment and chemotherapy as follows: abiraterone acetate plus prednisone (abiraterone)-docetaxel (ABI-DOCE), abiraterone-enzalutamide (ABI-ENZA), abiraterone–radium-223 (ABI-RAD), docetaxel-abiraterone (DOCE-ABI), docetaxel-cabazitaxel (DOCE-CABA), docetaxel-enzalutamide (DOCE-ENZA), and enzalutamide-docetaxel (ENZA-DOCE).Outcome measurements and statistical analysis: Baseline patient characteristics, quality of life, mCRPC treatments, and efficacy outcomes (progression and survival) were presented descriptively.Results and limitations: Data from 727 patients were eligible for the analysis (ABI-DOCE n = 178, ABI-ENZA n = 99, ABI-RAD n = 27, DOCE-ABI n = 191, DOCE-CABA n = 74, DOCE-ENZA n = 116, and ENZA-DOCE n = 42). Demographics and disease characteristics among patients between different sequences varied greatly. Most patients who started on abiraterone or enzalutamide stopped therapy because of disease progression. No randomisation to allow treatment/sequence comparisons limited this observational study.Conclusions: The real-world PCR data complement clinical trial data, reflecting more highly selected patient populations than seen in routine clinical practice. Baseline characteristics play a role in mCRPC first-line treatment selection, but other factors, such as treatment availability, have an impact. Efficacy observations are limited and should be interpreted with caution.Patient summary: Baseline characteristics appear to have a role in the first-line treatment selection of metastatic castration-resistant prostate cancer in the real-world setting. First-line abiraterone acetate plus prednisone seems to be the preferred treatment option for older patients and those with lower Gleason scores, first-line docetaxel for younger patients and those with more advanced disease, and first-line enzalutamide for patients with fewer metastases and more favourable performance status. The benefit to patients from these observations remains unknown.
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| 7. |
- Bobjer, Johannes, et al.
(författare)
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Location of retroperitoneal lymph node metastases in upper tract urothelial carcinoma : results from a prospective lymph node mapping study
- 2023
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 57, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC).Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND).Design, setting, and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node–positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates.Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used.Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates.Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited.Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.
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| 8. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma
- 2020
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 20, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells (Tregs) and M2 macrophages have been hypothesized to contribute to tumor progression. We found that M2 macrophages and Tregs are associated with more aggressive renal cell carcinoma, and that they have a synergistic effect on clinical outcome. Background: It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity. Objective: To investigate the association between infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs with clinical outcomes in renal cell carcinoma patients. Design, setting, and participants: A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163+ M2 macrophage and CD4+FOXP3+ Treg infiltration by immunohistochemistry. Outcome measurements and statistical analysis: Associations between clinicopathological features and infiltration of CD163+ M2 macrophages and/or CD4+FOXP3+ Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. Results and limitations: We found that infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163+ M2 macrophages and CD4+FOXP3+ Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation. Conclusions: Infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome. Patient summary: The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes.
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| 9. |
- Ekerhult, Teresa, et al.
(författare)
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Ectopic Germinal Centres with B and T Cells and Follicular Dendritic Cell Networks in Urethral Stricture Tissue: Possible Avenue for Immunological Treatments
- 2021
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 27, s. 88-93
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Tidskriftsartikel (refereegranskat)abstract
- Background: The underlying cause of a urethral stricture can sometimes be obscure. It is possible that an injury to the urethra induces an immunological cascade that generates scar tissue and fibrosis, eventually resulting in a stricture. If such immuno-logical reactions could be better elucidated, immunological therapies could possibly emerge. Objective: To evaluate if ectopic germinal centres exist in urethral stricture disease. Design, setting, and participants: Resected stricture specimens from 45 patients undergoing open bulbar urethroplasty with excision and anastomosis were assessed. Histopathological characteristics, such as fibrosis (grade I & ndash;III), inflammation, and scle-rosis, were evaluated using immunostaining for CD3 (T cells), CD20 (B cells), and CD21 (follicular dendritic cells). Outcome measurements and statistical analysis: The primary outcome measure was the presence or absence of a germinal centre. The secondary outcome was evaluation of any correlation between the degree of fibrosis and germinal centres. Fisher & rsquo;s exact test was used for univariate analysis. Results and limitations: In six patients, ectopic germinal centres were found. In ten patients, there was no inflammation at all. There was no correlation found between the degree of fibrosis and the abundance of immunohistochemically detected immune cells. Conclusions: Ectopic germinal centres, with B and T cells as well as follicular dendritic cell networks, do exist in urethral stricture disease. This finding may open up for novel research avenues on the possibility of adopting immunological treatments for urethral stricture disease. Patient summary: In patients with a narrowing of the urethra due to any kind of trauma, we looked for the presence of centres of immunological reaction in urethral tissue. We identified these immunological centres (also called germinal centres) in some patients. This intriguing finding suggests that immunological treatments may have potential for men with scar tissue in a narrowed urethra. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creati-vecommons.org/licenses/by-nc-nd/4.0/).
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| 10. |
- Gatto, Francesco, 1987, et al.
(författare)
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Plasma and Urine Free Glycosaminoglycans as Monitoring Biomarkers in Nonmetastatic Renal Cell Carcinoma—A Prospective Cohort Study
- 2022
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1683 .- 2666-1691. ; 42, s. 30-39
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Tidskriftsartikel (refereegranskat)abstract
- Background: No liquid biomarkers are approved in renal cell carcinoma (RCC), making early detection of recurrence in surgically treated nonmetastatic (M0) patients dependent on radiological imaging. Urine- and plasma free glycosaminoglycan profiles—or free GAGomes—are promising biomarkers reflective of RCC metabolism. Objective: To explore whether free GAGomes could detect M0 RCC recurrence noninvasively. Design, setting, and participants: Between June 2016 and February 2021, we enrolled a prospective consecutive series of patients elected for (1) partial or radical nephrectomy for clinical M0 RCC (cohort 1) or (2) first-line therapy following RCC metachronous metastatic recurrence (cohort 2) at Sahlgrenska University Hospital, Gothenburg, Sweden. The study population included M0 RCC patients with recurrent disease (RD) versus no evidence of disease (NED) in at least one follow-up visit. Plasma and urine free GAGomes—consisting of 40 chondroitin sulfate (CS), heparan sulfate, and hyaluronic acid (HA) features—were measured in a blinded central laboratory preoperatively and at each postoperative follow-up visit until recurrence or end of follow-up in cohort 1, or before treatment start in cohort 2. Outcome measurements and statistical analysis: We used Bayesian logistic regression to correlate GAGome features with RD versus NED and with various histopathological variables. We developed three recurrence scores (plasma, urine, and combined) proportional to the predicted probability of RD. We internally validated the area under the curve (AUC) using bootstrap resampling. We performed a decision curve analysis to select a cutoff and report the corresponding net benefit, sensitivity, and specificity of each score. We used univariable analyses to correlate each preoperative score with recurrence-free survival (RFS). Results and limitations: Of 127 enrolled patients in total, 62 M0 RCC patients were in the study population (median age: 63 year, 35% female, and 82% clear cell). The median follow-up time was 3 months, totaling 72 postoperative visits —17 RD and 55 NED cases. RD was compatible with alterations in 14 (52%) of the detectable GAGome features, mostly free CS. Eleven (79%) of these correlated with at least one histopathological variable. We developed a plasma, a urine, and a combined free CS RCC recurrence score to diagnose RD versus NED with AUCs 0.91, 0.93, and 0.94, respectively. At a cutoff equivalent to ≥30% predicted probability of RD, the sensitivity and specificity were, respectively, 69% and 84% in plasma, 81% and 80% in urine, and 80% and 82% when combined, and the net benefit was equivalent to finding an extra ten, 13, and 12 cases of RD per hundred patients without any unnecessary imaging for plasma, urine, and combined, respectively. The combined score was prognostic of RFS in univariable analysis (hazard ratio = 1.90, p = 0.02). Limitations include a lack of external validation. Conclusions: Free CS scores detected postsurgical recurrence noninvasively in M0 RCC with substantial net benefit. External validity is required before wider clinical implementation. Patient summary: In this study, we examined a new noninvasive blood and urine test to detect whether renal cell carcinoma recurred after surgery.
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