Robot-assisted partial nephrectomy (RAPN) is used more and more in present days as a therapy option for surgical treatment of cT1 renal masses. Current guidelines equally recommend open (OPN), laparoscopic (LPN), or robotic partial nephrectomy (PN). The aim of this review was to analyze the most representative RAPN series in terms of reported oncological outcomes. (2) Methods: A systematic search of Webofscience, PUBMED, Clinicaltrials.gov was performed on 1 August 2022. Studies were considered eligible if they: included patients with renal cell carcinoma (RCC) stage T1, were prospective, used randomized clinical trials (RCT) or retrospective studies, had patients undergo RAPN with a minimum follow-up of 48 months. (3) Results: Reported positive surgical margin rates were from 0 to 10.5%. Local recurrence occurred in up to 3.6% of patients. Distant metastases were reported in up to 6.4% of patients. 5-year cancer free survival (CFS) estimates rates ranged from 86.4% to 98.4%. 5-year cancer specific survival (CSS) estimates rates ranged from 90.1% to 100%, and 5-year overall survival (OS) estimates rated ranged from 82.6% to 97.9%. (4) Conclusions: Data coming from retrospective and prospective series shows very good oncologic outcomes after RAPN. Up to now, 10-year survival outcomes were not reported. Taken together, RAPN deliver similar oncologic performance to OPN and LPN.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Therapies combining either two immune check-point inhibitors (ICIs) or an ICI and a tyrosine kinase inhibitor (TKI) have been shown to improve overall survival (OS), progression-free survival (PFS) and objective response rates (ORR) in metastatic renal cell carcinoma (mRCC); moreover, unprecedented rates of complete remission (CR) have been reported. AREAS COVERED: Among six randomized trials of ICI combinations, four have outperformed the TKI sunitinib in terms of OS. The CheckMate 214 trial investigated the combination of nivolumab (a programmed cell death protein 1 [PD-1] inhibitor) and ipilimumab (a cytotoxic T-lymphocyte antigen-4 [CTLA-4)] inhibitor). Three other trials evaluated combinations of an ICI and a TKI. These combinations are: 1) pembrolizumab (PD-1 inhibitor) plus axitinib, 2) nivolumab plus cabozantinib, and 3) pembrolizumab plus lenvatinib. This short review addresses the findings of these trials, comparing outcomes and discussing the challenges of decision-making in clinical practice. EXPERT OPINION: Not all patients benefit from ICI combinations. Predictive biomarkers and new therapeutic approaches are urgently needed to overcome treatment failures. A growing understanding of immune escape mechanisms and the interplay between the immune response and the gut microbiota may offer additional rescue strategies beyond ICIs and TKIs.
Patients with upper tract urothelial carcinoma (UTUC) often have a delayed diagnosis and by then, present with advanced disease which has been shown to be associated with lymphovascular invasion (LVI). It has been suggested to be involved in the metastatic cascade of the disease. In this review, we provide an extensive up-to-date summary of the current knowledge about the prognostic impact of LVI in patients undergoing radical nephroureterectomy (RNU). A systematic search of PubMed/MEDLINE, Scopus, EMBASE, and Web of Science for all reports published from 2010 through 2021 was performed. We performed pooled analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of series that evaluated LVI as a prognostic factor in adults with UTUC who underwent RNU. The assessed oncological outcomes were disease recurrence, cancer-specific and overall survival. A meta-regression analysis was used to explore potential heterogeneity. A total of 58 series met the eligibility criteria for qualitative and quantitative synthesis. We included 29,829 patients, ranging from 101 to 2492 per study. All series were retrospective. LVI was present in 7,818 patients (26.2%). The median age of the patients was 69 years and the median follow-up was 40 months. In 40 of 58 studies (68.9%), adjuvant chemotherapy was given. The pooled HRs show that LVI predicts a greater risk of recurrence of the disease (pooled HR 1.43, 95% CI: 1.31-1.55, P = 0.000; I2 = 76.3%), and decreases cancer-specific survival (pooled HR 1.53, 95% CI: 1.41-1.66, P = 0.000; I2 = 72.3%) and overall survival (HR 1.56, 95% CI 1.45-1.69, P = 0.000; I2 = 62.9%). It can be concluded that LVI is a common histologic pattern in surgical specimen in patients undergoing RNU for UTUC. LVI predicts a greater risk of recurrence and mortality, thus it should be carefully assessed in clinical practice to determine prognosis, and for optimal decision-making within the concept of personalized therapies.
- MeSH
- karcinom z přechodných buněk * patologie MeSH
- lidé MeSH
- lokální recidiva nádoru chirurgie MeSH
- nádory močového měchýře * chirurgie MeSH
- nádory močovodu * patologie MeSH
- nefroureterektomie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
PURPOSE OF REVIEW: To perform indirect comparisons of efficacy and safety of first-line immune checkpoint inhibitor (ICI)-based combination therapies for renal cell carcinoma with sarcomatoid features (sRCC). RECENT FINDINGS: Five trials were included in our network meta-analyses comprising 568 patients. The combinations nivolumab plus ipilimumab and nivolumab plus cabozantinib achieved significant improvement of progression-free survival (PFS), overall survival (OS), and objective response rates (ORR). Nivolumab plus ipilimumab was associated with the highest likelihood of achieving a complete response. All the included combinations significantly improved PFS and ORR. The combinations of pembrolizumab plus axitinib did not show a statistically significant association with OS. Nivolumab plus cabozantinib had the highest likelihood of improving PFS and OS. SUMMARY: Our network meta-analysis demonstrates that sRCC are responsive to immune-based combinations. The dual ICI with nivolumab plus ipilimumab improved all efficacy outcomes and achieved the highest complete response rates (CRR). Although the association of nivolumab plus cabozantinib with CRR was not statistically significant, this combination demonstrated the highest likelihood of PFS and OS improvements.
- MeSH
- imunoterapie škodlivé účinky MeSH
- ipilimumab terapeutické užití MeSH
- karcinom z renálních buněk * MeSH
- lidé MeSH
- nádory ledvin * MeSH
- nádory měkkých tkání * MeSH
- nivolumab terapeutické užití MeSH
- sarkom * MeSH
- síťová metaanalýza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
CONTEXT: Immune-checkpoint inhibitors (ICIs) are a mainstay treatment of metastatic renal cell carcinoma (mRCC). As not all patients benefit from ICIs, a biomarker-driven clinical decision-making strategy is desirable. OBJECTIVE: To assess the predictive value of programmed death ligand 1 (PD-L1) in mRCC patients treated with ICIs. EVIDENCE ACQUISITION: Multiple databases were searched for articles published up to April 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies comparing objective response rate (ORR), complete response rate (CRR), progressive disease rate (PDR), or progression-free survival (PFS) based on tumor PD-L1 status in mRCC patients were eligible. EVIDENCE SYNTHESIS: Six studies matched our eligibility criteria. Treatment with ICIs was associated with significantly higher ORRs and CRRs, and lower PDRs in patients with PD-L1-positive tumors than in those with PD-L1-negative status (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.48-2.28; OR 3.11, 95% CI 2.04-4.75; and OR 0.43, 95% CI 0.31-0.60, respectively). ICI treatment was associated with significantly better PFS in PD-L1-positive patients than in sunitinib-treated patients (hazard ratio 0.65, 95% CI 0.57-0.74), whereas this was not found in patients with PD-L1-negative tumors. Compared with sunitinib, ICI combination therapy improved ORRs and PFS significantly in PD-L1-positive patients of all examined ICIs. Nivolumab plus ipilimumab had the highest likelihood of providing the highest ORR and longest PFS in PD-L1-positive patients. CONCLUSIONS: PD-L1 positivity of the tumor is associated with improved ORRs and prolonged PFS in mRCC patients receiving ICI treatment and thus helps identify mRCC patients most likely to benefit from ICI treatment. PATIENT SUMMARY: The use of an immune-checkpoint inhibitor for the treatment of metastatic renal cell carcinoma (mRCC) improved oncological outcomes, and the status of programmed death ligand 1 could contribute to guiding patients and clinicians when determining personalized treatment strategies for mRCC.
OBJECTIVE: To identify the available evidence on aerosol viral transmission risk during minimally invasive surgery (MIS) and evaluate its impact on guidelines development and clinical activity worldwide during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We performed a scoping review on PubMed, Cochrane, the Excerpta Medica dataBASE (EMBASE), Clinical Trial Register, and the Grey Literature Repository databases, to identify reports on viral transmission via surgical smoke or aerosolisation. A systematic review of all available national and international guidelines was also performed to report their recommendations. Additionally, a worldwide transdisciplinary survey was performed to capture the actual compliance to dedicated guidelines and their impact on MIS activity. RESULTS: Based on a selection of 17 studies, there was no evidence to support the concerns of an intraoperative viral transmission via pneumoperitoneum aerosolisation. Most national surgical and urological societies either did address this topic or referred to international guidelines. The guidelines of the American College of Surgery, the Royal College of Surgeons, and the European Association of Urology Robotic Urology Section, recommended an avoidance of MIS due to an increased risk of intraoperative aerosol-enhanced transmission. The results of the survey completed by 334 respondents, from different surgical abdominal specialties, suggested a lack of compliance with the guidelines. CONCLUSION: There seems to be a dissonance between contemporary guidelines and ongoing surgical activity, possibly due to the perceived lack of evidence. Recommendations regarding changes in clinical practice should be based on the best available research evidence and experience. A scoping review of the evidence and an assessment of the benefits and harms together with a survey showed that laparoscopic procedures do not seem to increase the risk of viral transmission. Nevertheless, the few publications and low quality of existing evidence limits the validity of the review.
- MeSH
- aerosoly * MeSH
- COVID-19 epidemiologie přenos MeSH
- dodržování směrnic * MeSH
- kontrola infekce * MeSH
- lékařská praxe - způsoby provádění MeSH
- lidé MeSH
- miniinvazivní chirurgické výkony škodlivé účinky MeSH
- pandemie MeSH
- peroperační doba MeSH
- přenos infekce z pacienta na zdravotnického pracovníka prevence a kontrola MeSH
- rizikové faktory MeSH
- SARS-CoV-2 MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE OF REVIEW: The purpose of this review is to evaluate the risk of intraoperative aerosol viral transmission and the impact of updated COVID-19 guidelines on minimally invasive surgery (MIS) in Austria. RECENT FINDINGS: The current literature does not support the risk of intraoperative viral transmission nor does it suggest a harm of minimally invasive procedures in the context of the COVID-19 pandemic. However, medical societies mostly adopted a precautionary approach with a focus on protective measures. Austrian surgeons considered MIS safe during the pandemic and Austria managed to keep the initial outbreak in control. Yet, MIS programs were still affected due to the postponements of elective procedures and switches to other methods by some surgeons. SUMMARY: The postponement and cancellation of MIS caused complexities in health-care delivery in Austria, whilst the evidence to substantiate this precautionary approach is missing. It must be noted, both the guidelines and our review are limited by the scarcity of evidence. In further consequence, regional factors should be considered while taking precautions. Specific studies on the severe acute respiratory syndrome coronavirus type 2 transmission risk during MIS are urgently needed.
- MeSH
- aerosoly MeSH
- COVID-19 * MeSH
- lidé MeSH
- miniinvazivní chirurgické výkony MeSH
- pandemie * MeSH
- SARS-CoV-2 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Rakousko MeSH
PURPOSE OF REVIEW: To compare the safety profiles of systemic immune checkpoint inhibitor-based combination therapies that were evaluated in the first-line setting of the management of patients with advanced or metastatic renal cell carcinoma (mRCC). RECENT FINDINGS: Six phase III randomized control trials comparing first-line immune-based combination therapies to sunitinib in previously untreated patients with mRCC. Network meta-analyses were conducted to compare treatment-related adverse events (TRAEs), treatment discontinuation, and treatment-related mortality. SUMMARY: Lenvatinib plus pembrolizumab was associated with the highest likelihood of grade ≥3 TRAEs, and treatment discontinuation rates. Nivolumab plus ipilimumab was associated with the lowest rates of grade ≥3 TRAEs. However, it was associated with a higher likelihood of endocrine-related adverse events (AEs). A higher likelihood of high-grade diarrhea was associated with pembrolizumab plus axitinib and avelumab plus axitinib. All combinations showed low rates of hematological AEs.
- MeSH
- axitinib MeSH
- karcinom z renálních buněk * farmakoterapie MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie MeSH
- síťová metaanalýza MeSH
- sunitinib MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
PURPOSE OF REVIEW: To discuss treatment decisions in the first-line setting of metastatic renal cell carcinoma (mRCC). RECENT FINDINGS: Immune check point inhibitor (ICI) combinations have replaced sunitinib as the standard of care in the first-line treatment of mRCC. Dual ICI treatment with nivolumab and ipilimumab was shown to significantly improve overall survival and objective response rates. Similarly, the ICI-tyrosine kinase inhibitor combinations pembrolizumab and axitinib and nivolumab and cabozantinib have demonstrated superiority in terms of overall survival, objective response rates and progression-free survival versus sunitinib. The lack of both comparative trials and predictive markers impedes individualized treatment decisions. Clinicians are left to make treatment choices based on clinical and biological factors. These factors may include differences in toxicity profiles, the rate of complete remission, a clinical situation that requires urgent tumor shrinkage, the presence of inflammation, histological or immune-histochemical features and others. SUMMARY: In the absence of comparative trials, clinical and biological factors may facilitate the choice between various treatment options in the first-line setting of mRCC. In addition, both the experience of the physician with a specific treatment together with patient's preferences and expectations of systemic therapy may be part of the decision-making process.
- MeSH
- axitinib škodlivé účinky MeSH
- inhibitory proteinkinas škodlivé účinky MeSH
- karcinom z renálních buněk * farmakoterapie MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
CONTEXT: There have been substantial changes in the management of patients with metastatic renal cell carcinoma (mRCC) over the past decade, with upfront immunotherapy-based combinations replacing targeted therapies. A broad range of combinations have been approved, and comparisons of their efficacy and safety are needed to guide the optimal choice of first-line therapy. OBJECTIVE: To perform indirect comparisons of efficacy and safety of first-line immune checkpoint inhibitor (ICI)-based combination therapies for mRCC. EVIDENCE ACQUISITION: We searched multiple databases and abstracts of major scientific meetings up to February 2021 to identify phase III randomized controlled trials of patients receiving first-line ICI-based combination therapies for mRCC. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included complete response rates (CRRs), objective response rates (ORRs), grade ≥3 treatment-related adverse events (TRAEs), and rates of treatment discontinuation due to adverse events (AEs). Subgroup network meta-analyses were performed based on patients' risk group categories and programmed death ligand 1 (PD-L1) expression status. EVIDENCE SYNTHESIS: Six trials were included in our network meta-analyses comprising 5121 patients. Nivolumab plus cabozantinib had the highest likelihood of providing the maximal OS (P score: 0.7573). Lenvatinib plus pembrolizumab demonstrated the highest likelihood of PFS (P score: 0.9906) and ORR (P score: 0.9564). CRRs were more likely to be associated with nivolumab plus ipilimumab (P score: 0.8682). In patients with ≥1% PD-L1 expression, the highest likelihood of better PFS was associated with lenvatinib plus pembrolizumab and nivolumab plus ipilimumab. Nivolumab plus ipilimumab was also associated with the lowest rates of grade ≥3 TRAEs; while the highest likelihood of AE-related treatment discontinuation was associated with lenvatinib plus pembrolizumab and nivolumab plus ipilimumab. CONCLUSIONS: Our network meta-analysis suggests that combinations of ICIs and tyrosine kinase inhibitors (TKIs) provide superior PFS, ORR, and OS to ICI-ICI combinations, regardless of the on International mRCC Database Consortium risk group. However, an ICI-ICI combination could be the optimal treatment for tumors with increased PD-L1 expression. The newly introduced ICI-TKI combinations, nivolumab plus cabozantinib and lenvatinib plus pembrolizumab, showed promising activity and are likely to have an important role in the mRCC treatment strategy. PATIENT SUMMARY: The use of immune checkpoint inhibitor (ICI)-based combinations (ICI plus tyrosine kinase inhibitor and ICI-ICI) improved oncological outcomes of metastatic renal cell carcinoma. Programmed death ligand 1 (PD-L1) expression status could help guide physicians and patients to select the appropriate treatment strategy.
