| 1. |
- Abu-Ghanem, Yasmin, et al.
(författare)
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Should patients with low-risk renal cell carcinoma be followed differently after nephron-sparing surgery vs radical nephrectomy?
- 2021
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Ingår i: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 128:3, s. 386-394
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether pT1 renal cell carcinoma (RCC) should be followed differently after partial (PN) or radical nephrectomy (RN) based on a retrospective analysis of a multicentre database (RECUR).Subjects: A retrospective study was conducted in 3380 patients treated for nonmetastatic RCC between January 2006 and December 2011 across 15 centres from 10 countries, as part of the RECUR database project. For patients with pT1 clear-cell RCC, patterns of recurrence were compared between RN and PN according to recurrence site. Univariate and multivariate models were used to evaluate the association between surgical approach and recurrence-free survival (RFS) and cancer-specific mortality (CSM).Results: From the database 1995 patients were identified as low-risk patients (pT1, pN0, pNx), of whom 1055 (52.9%) underwent PN. On multivariate analysis, features associated with worse RFS included tumour size (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14–1.39; P < 0.001), nuclear grade (HR 2.31, 95% CI 1.73–3.08; P < 0.001), tumour necrosis (HR 1.5, 95% CI 1.03–2.3; P = 0.037), vascular invasion (HR 2.4, 95% CI 1.3–4.4; P = 0.005) and positive surgical margins (HR 4.4, 95% CI 2.3–8.5; P < 0.001). Kaplan–Meier analysis of CSM revealed that the survival of patients with recurrence after PN was significantly better than those with recurrence after RN (P = 0.02). While the above-mentioned risk factors were associated with prognosis, type of surgery alone was not an independent prognostic variable for RFS nor CSM. Limitations include the retrospective nature of the study.Conclusion: Our results showed that follow-up protocols should not rely solely on stage and type of primary surgery. An optimized regimen should also include validated risk factors rather than type of surgery alone to select the best imaging method and to avoid unnecessary imaging. A follow-up of more than 3 years should be considered in patients with pT1 tumours after RN. A novel follow-up strategy is proposed.
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| 2. |
- Abu-Ghanem, Yasmin, et al.
(författare)
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The Impact of Histological Subtype on the Incidence, Timing, and Patterns of Recurrence in Patients with Renal Cell Carcinoma After Surgery : Results from RECUR Consortium
- 2021
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 4:3, s. 473-482
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current follow-up strategies for patients with renal cell carcinoma (RCC) after curative surgery rely mainly on risk models and the treatment delivered, regardless of the histological subtype.Objective: To determine the impact of RCC histological subtype on recurrence and to examine the incidence, pattern, and timing of recurrences to improve follow-up recommendations.Design, setting, and participants: This study included consecutive patients treated surgically with curative intention (ie, radical and partial nephrectomy) for nonmetastatic RCC (cT1–4, M0) between January 2006 and December 2011 across 15 centres from 10 countries, as part of the euRopEan association of urology renal cell carcinoma guidelines panel Collaborative multicenter consortium for the studies of follow-Up and recurrence patterns in Radically treated renal cell carcinoma patients (RECUR) database project.Outcome measurements and statistical analysis: The impact of histological subtype (ie, clear cell RCC [ccRCC], papillary RCC [pRCC], and chromophobe RCC [chRCC]) on recurrence-free survival (RFS) was assessed via univariate and multivariate analyses, adjusting for potential interactions with important variables (stage, grade, risk score, etc.) Patterns of recurrence for all histological subtypes were compared according to recurrence site and risk criteria.Results and limitations: Of the 3331 patients, 62.2% underwent radical nephrectomy and 37.8% partial nephrectomy. A total of 2565 patients (77.0%) had ccRCC, 535 (16.1%) had pRCC, and 231 (6.9%) had chRCC. The median postoperative follow-up period was 61.7 (interquartile range: 47–83) mo. Patients with ccRCC had significantly poorer 5-yr RFS than patients with pRCC and chRCC (78% vs 86% vs 91%, p = 0.001). The most common sites of recurrence for ccRCC were the lung and bone. Intermediate-/high-risk pRCC patients had an increased rate of lymphatic recurrence, both mediastinal and retroperitoneal, while recurrence in chRCC was rare (8.2%), associated with higher stage and positive margins, and predominantly in the liver and bone. Limitations include the retrospective nature of the study.Conclusions: The main histological subtypes of RCC exhibit a distinct pattern and dynamics of recurrence. Results suggest that intermediate- to high-risk pRCC may benefit from cross-sectional abdominal imaging every 6 mo until 2 yr after surgery, while routine imaging might be abandoned for chRCC except for abdominal computed tomography in patients with advanced tumour stage or positive margins.Patient summary: In this analysis of a large database from 15 countries around Europe, we found that the main histological subtypes of renal cell carcinoma have a distinct pattern and dynamics of recurrence. Patients should be followed differently according to subtype and risk score.
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| 3. |
- Bedke, Jens, et al.
(författare)
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2021 Updated European Association of Urology Guidelines on the Use of Adjuvant Pembrolizumab for Renal Cell Carcinoma
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:2, s. 134-137
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy.Patient summary: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.
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| 4. |
- Bedke, Jens, et al.
(författare)
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The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma : Immune Checkpoint Inhibitor–based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care
- 2021
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 80:4, s. 393-397
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. Patient summary: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
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| 5. |
- Bedke, Jens, et al.
(författare)
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The 2022 updated European association of urology guidelines on the use of adjuvant immune checkpoint inhibitor therapy for renal cell carcinoma
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:1, s. 10-14
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Tidskriftsartikel (refereegranskat)abstract
- In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient.Patient summary: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.
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| 6. |
- Bedke, Jens, et al.
(författare)
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Updated European Association of Urology Guidelines on Renal Cell Carcinoma : Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment-naïve Metastatic Clear-Cell Renal Cell Carcinoma
- 2021
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 79:3, s. 339-342
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Tidskriftsartikel (refereegranskat)abstract
- Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
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| 7. |
- Capitanio, Umberto, et al.
(författare)
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A renewal of the tnm staging system for patients with renal cancer to comply with current decision-making : Proposal from the European Association of Urology guidelines panel
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:1, s. 3-5
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Tidskriftsartikel (refereegranskat)abstract
- Risk classification for patients with renal cell carcinoma (RCC) is critical for clinical decision-making and ultimately for patient outcomes [1]. Staging is the single most informative piece of information for risk assessment in patients with cancer. Currently, the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM scheme is the most universally accepted staging system [2]. Since its first publication in 1977, the UICC/AJCC TNM staging system has changed while still retaining its characteristics of simplicity, reproducibility, and user-friendliness.
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| 8. |
- Capitanio, Umberto, et al.
(författare)
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Reply to Yaxiong Tang, Xu Hu, Kan Wu, Yanxiang Shao, and Xiang Li’s Letter to the Editor re: Umberto Capitanio, Jens Bedke, Laurence Albiges, et al. A Renewal of the TNM Staging System for Patients with Renal Cancer To Comply with Current Decision-making: Proposal from the European Association of Urology Guidelines Panel. Eur Urol. 2022;83:3–5
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:3, s. e74-e75
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Fallara, Giuseppe, et al.
(författare)
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Recurrence pattern in localized RCC : results from a European multicenter database (RECUR)
- 2022
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 40:11, s. 494.e11-494.e17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern.Material and methods: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed.Results: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18–3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01–1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64–1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study.Conclusions: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS.
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| 10. |
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