Current Opinion in Urology最新文献

Purpose of review: An update on the latest advances in the management of upper tract urothelial carcinoma (UTUC), with an emphasis on strategies to optimize oncologic outcomes while minimizing overtreatment.

Recent findings: Recent high-quality trials have changed the landscape of UTUC treatment. Emerging tools including 3D histology and measurement of cell free tumor DNA may improve diagnostic accuracy of disease grading and staging, and be used in monitoring treatment response. Novel therapies show promise of reducing low-grade UTUC disease recurrence at the cost of significant side-effects. Platinum-based neoadjuvant chemotherapy in high-grade/muscle-invasive disease showed complete pathological response in a subset of patients, but difficult to predict responders. Adjuvant platinum-based chemotherapy exhibited a clear survival benefit, but immunotherapy did not, suggesting possible overtreatment with these agents. Molecularly-targeted therapies in metastatic UTUC have shown the greatest recent oncologic advances, but exhibit a high adverse event-rate.

Summary: Low-grade UTUC has the potential for overtreatment, as it exhibits low metastatic-potential and excellent survival. For high-grade and advanced-stage UTUC, these carry high mortality rates and require more aggressive treatment, but studies are limited by inaccurate grading and staging which can lead to overtreatment especially in the neoadjuvant setting. Emerging technologies will help improve diagnostic accuracy and noninvasive monitoring of treatment response.

Purpose of review: Management of upper tract urothelial cancer (UTUC) has been largely extrapolated from bladder cancer due to its rarity; however, unique biological and clinical differences between UTUC and bladder cancer have been uncovered. The purpose of this review is to present the current therapeutic landscape of UTUC with an emphasis on biologically driven rationale.

Recent findings: Prospective trials for patients with high-risk localized UTUC have shown improved outcomes with adjuvant and neoadjuvant platinum-based chemotherapy. However, the timing of therapy relative to nephroureterectomy may impact platinum eligibility due to renal functional decline following surgery. In recent years, emerging therapeutic classes including immune checkpoint inhibition, antibody drug conjugates, and targeted therapies have emerged as tolerable alternatives to platinum-based chemotherapy in treating metastatic disease. Biomarker-selected therapies, including those targeting HER2 and FGFR3, have shown encouraging results and are relevant to UTUC based on increased expressions of these targets; however, no prospective study to date has been powered to assess the effect of these modern treatments on patients with UTUC specifically.

Summary: Unique biological insights into UTUC pathogenesis and risk factors have expanded the therapeutic landscape for these patients beyond conventional platinum-based chemotherapeutic approaches. Novel therapeutic classes have emerged to guide more precise approaches in treating patients with urothelial cancer, with a need for further trials powered specifically to the UTUC population.

Purpose of review: To provide a comprehensive overview of existing and future paradigms for perioperative systemic therapy in the treatment of upper tract urothelial carcinoma.

Recent findings: Contemporary treatment paradigms for the management of upper tract urothelial carcinoma focus on use of neoadjuvant cisplatin based chemotherapy for high grade disease primarily based on two small single arm phase II clinical trials. More robust evidence from a phase III randomized clinical trial exists for the use of adjuvant platinum based chemotherapy for invasive disease after radical nephroureterectomy, but there are significant concerns about renal function and platinum eligibility after nephroureterectomy. There are currently ongoing clinical trials for nonplatinum based perioperative systemic therapies including checkpoint inhibitors/immunotherapy as well as antibody-drug conjugates, but currently no recommendation can be made for these approaches.

Summary: Current evidence supports neoadjuvant cisplatin chemotherapy in the setting of high grade disease or concern for significant renal dysfunction after radical nephroureterectomy or platinum based adjuvant chemotherapy in eligible patients with advanced disease after surgery. While there is no established role for nonplatinum based therapies yet, multiple ongoing trials exploring use of immunotherapies and antibody-drug conjugates as monotherapy or combination may provide new therapeutic options in this population.

Purpose of review: In recent years, intraluminal therapies have become a valid alternative for low grade upper tract urothelial carcinoma (UTUC) patients, as overall survival and cancer-specific survival rates were shown to be comparable to those achieved with radical nephroureterectomy for selected cases. Nonetheless, endoscopic treatment has its limitations. As technology progresses and the demand for endoscopic treatments increases, intraluminal chemotherapy and immunotherapy instillations within the upper tract have increasingly become the subject areas of research.

Recent findings: The main intraluminal therapies and relevant instillation approaches are reviewed in this study, including recent publications and their main outcomes. The recurrence rates demonstrated in the literature strengthen the notion that patients with UTUC following current intraluminal treatments have a better prognosis than in the past. Updated relevant guidelines regarding surveillance among this population are also reviewed and summarized.

Summary: The treatment of upper tract urothelial carcinoma is clinically challenging. Developments in recent years show promising results in this field and ongoing research with new developments is emerging. Further studies are required to better understand the contribution of intraluminal therapies to the management of this disease.

Purpose of review: This review provides an overview of the recent publications on kidney-sparing-surgery (KSS) for upper tract urothelial carcinoma (UTUC), an alternative to radical nephroureterectomy (RNU) for an increasing number of indications.

Recent findings: Recent studies highlight comparable survival outcomes between KSS [ureterorenoscopy with tumour ablation (URS) or segmental ureteral resection (SUR)] and RNU, even in high-risk UTUC patients. KSS has shown to preserve renal function without significantly compromising oncologic control in appropriately selected patients. Included literature also researched surgical complications, surveillance strategies, such as second-look ureteroscopy, and comparative cost analyses.

Summary: Over the past two and a half years, studies have emphasized the growing usage of URS and SUR in treating selected UTUC patients. Recent literature has remarkably included relatively large numbers of typically high-risk patients with features such as high-grade tumours, stage >Ta, multifocality, and hydronephrosis with acceptable results. Further research should expand on the different indications for KSS, its postoperative surveillance and comparative economic analyses.

Purpose of review: Bladder cancer is a substantial burden for public health worldwide. A risk-adapted treatment strategy is required for non muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). To date, treatment includes surgery with or without peri-operative local or systemic treatment. The aim of this review was to explore novel intravesical therapies and delivery systems emerging in NMIBC and MIBC.

Recent findings: Several novel intravesical therapies and delivery systems for NMIBC and MIBC treatment recently emerged. Hyperthermic intravesical chemotherapy (HIVEC) allows a reasonable cancer control in selected high-risk NMIBC. Novel intravesical drugs such as nadofaragene firadenovec, Oncofid-P-B or Nogapendekin alfa-inbakicept seem to be safe and well tolerated. However, their efficacy in high-risk NMIBC should be further investigated. Hydrogels appear to be safe, well tolerated and potentially efficient in primary chemoablation in selected cases of low-grade intermediate-risk NMIBC tumors. Drug-releasing intravesical systems (drug-RIS) such as TAR-200 are safe and well tolerated, providing high partial and complete response rate in both NMIBC and MIBC patients.

Summary: The armamentarium for the treatment of bladder cancer patients is expanding, notably with HIVEC, hydrogels, drug-RIS and novel therapies. However, accurate patients' selection is key to prevent disease progression in any bladder-sparing strategy, and radical cystectomy remains the gold-standard to date.

Purpose of review: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for metastatic renal cell carcinoma (mRCC), significantly improving overall survival and achieving durable responses. This review is timely due to the increasing number of ICI-based regimens now considered standard care for RCC. There is an urgent need to identify reliable biomarkers that can predict therapeutic responses and resistance, a key challenge in current research.

Recent findings: While tumor-specific factors such as pathological characteristics, genomic mutations, and transcriptional profiles have been extensively studied, no definitive predictive biomarker has yet emerged. Additionally, advanced technologies are being explored to address tumor heterogeneity. Recent research has focused on novel areas such as the microbiome, radiomics, and spatial transcriptomics, which show promise as potential biomarkers.

Summary: The translation of these emerging biomarker findings into clinical practice is essential to improving personalized treatment strategies for RCC. Until reliable biomarkers are clinically available, clinical factors may play a pivotal role in guiding individualized treatment decisions to optimize patient outcomes.

Purpose of review: Renal cell carcinoma (RCC) is resistant to chemotherapy. Adjuvant interferon and tyrosine kinase inhibitors were ineffective. Immune checkpoint inhibitors (ICIs), however, have shed new hope in this setting. In the current review, updated evidence of adjuvant therapy in RCC is summarized.

Recent findings: KEYNOTE-564 demonstrated survival benefits of adjuvant Pembrolizumab in RCC. EAU guidelines now recommend adjuvant pembrolizumab to ccRCC patients at an increased risk of recurrence, as defined in the study. At a median follow-up of 24 months, the disease-free survival (DFS) was significantly longer for the Pembrolizumab group than placebo group [DFS 77.3 vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval (95% CI), 0.53-0.87; P  = 0.002]. From its updated analysis, at median follow up of 57.2 months, overall survival (OS) benefit of Pembrolizumab was demonstrated (hazard ratio for death, 0.62; 95% CI, 0.44-0.87; P  = 0.005). A number of other adjuvant ICI trials have though been negative.

Summary: Pembrolizumab is currently the only adjuvant therapy for RCC showing survival benefits, amid a number of negative trials on adjuvant immunotherapy. Currently, there is no role for adjuvant tyrosine-kinase inhibitors and radiotherapy for RCC. Meanwhile, a multidisciplinary approach and shared decision-making should be adopted.