European urology focus最新文献

Background and objective: Belzutifan, a hypoxia-inducible factor 2 alpha inhibitor, was approved initially for patients with von Hippel-Lindau disease and more recently for sporadic, metastatic clear cell renal cell carcinoma (ccRCC) based on the results of LITESPARK-005. There is a paucity of data regarding real-world experience with belzutifan in patients with sporadic, metastatic ccRCC. This study aims to describe clinical outcomes with belzutifan in patients with sporadic, metastatic ccRCC.

Methods: A retrospective study of 22 patients who received belzutifan at MD Anderson Cancer Center prior to the Food and Drug Administration approval was conducted. Progression-free survival (PFS) and objective response rate (ORR) were assessed by a blinded radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. PFS and overall survival (OS) were measured from belzutifan initiation.

Key findings and limitations: The median follow-up time was 14.9 mo. Most patients had International Metastatic RCC Database Consortium intermediate-risk disease, more than three metastatic sites, and a median of five prior lines of treatment at initiation of belzutifan; all patients received prior immune checkpoint therapy (ICT) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). The median PFS was 8.51 mo (95% confidence interval [CI] 0-18.4) and ORR was 36.4%. The median OS was 14.72 mo (95% CI 7.34-22.10). Of 22 patients, four (18.2%) patients required dose reductions and three (13.6%) patients discontinued belzutifan because of adverse drug events (ADEs). The most common ADEs were anemia (77.3%; 17/22) and hypoxia (36.4%; 8/22). There were no treatment-related deaths.

Conclusions and clinical implications: In a heavily pretreated cohort of patients with sporadic, metastatic ccRCC, belzutifan had meaningful clinical activity and was well tolerated. These real-world results add to the results of LITESPARK-005 and support the use of belzutifan after progression on ICT and VEGFR-TKIs.

Patient summary: Belzutifan is a new medicine used to treat a type of clear cell kidney cancer that has spread to other parts of the body (metastasized). A study at MD Anderson Cancer Center followed 22 patients who were treated with belzutifan, and found that it worked to control the cancer for almost 9 mo and caused the cancer to shrink in 36% of patients. This study confirms that belzutifan can be effective and safe, even after other treatments have not worked.

Background and objective: It is unclear whether cytoreductive nephrectomy (CN) practices have changed in the USA after the publication of the Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) trial in 2018. Our primary objective is to determine the effect of the CARMENA trial on CN rates in the USA.

Methods: Patients were identified in the National Cancer Database from 2004 to 2020. A quasiexperimental difference-in-differences analysis was used to test the primary outcome, as follows: the change in CN rate was assessed among metastatic clear cell renal cell carcinoma (ccRCC) patients diagnosed before versus after 2018, while using the localized nephrectomy (LN) rate performed in the setting of nonmetastatic ccRCC as a control group.

Key findings and limitations: The difference-in-differences analysis identified a statistically significant decrease in CN rate after CARMENA (β-coefficient [standard error]: -0.06 [0.025], p = 0.028), with a 10.2% absolute and a 31.8% relative rate reduction when compared with the counterfactual (expected) value (34.7% → 21.9% [actual] vs 32.1% [expected]). Primarily, relative differences in CN and LN rates before and after 2018 may be attributable to additional factors, aside from CARMENA publication, not tested in this quasiexperimental model.

Conclusions and clinical implications: CN rates decreased significantly after the publication of the CARMENA trial in 2018, with a minimal difference in regional or demographic practice patterns. Overall, the publication of the CARMENA trial results is seemingly associated with substantial alteration of clinical practice in the USA, with relatively broad and nonspecific adoption across facilities, regions, and demographics.

Patient summary: For decades, the immediate surgical removal of the kidney tumor (cytoreductive nephrectomy) was a mainstay of metastatic kidney cancer treatment. In 2018, the CARMENA study showed that patients treated with systemic therapy alone had similar outcomes to patients who underwent cytoreductive nephrectomy first. In this study, we show that fewer cytoreductive nephrectomies were performed after the CARMENA trial results were published.

Background and objective: Sequential intravesical gemcitabine/docetaxel (Gem/Doce) has emerged as a potential alternative to bacillus Calmette-Guérin (BCG) for the treatment of non-muscle-invasive bladder cancer (NMIBC). Our aim was to determine the comparative effectiveness of BCG and Gem/Doce for patients with intermediate-risk (IR) NMIBC, composed mainly of high-grade (HG) Ta disease.

Methods: Patients with IR-NMIBC who received either BCG or Gem/Doce during 2013-2023 were included. Maintenance BCG (as per the Southwest Oncology Group protocol) and monthly Gem/Doce maintenance for 1 yr were offered to patients with no evidence of recurrence after induction. Routine surveillance with cystoscopy was performed according to the American Urological Association guidelines. The Kaplan-Meier method was used to assess high-grade and any-grade recurrence-free survival (RFS). Cox regression analysis was performed to find predictors of recurrence.

Key findings and limitations: Of 483 patients, 127 had IR-NMIBC; 66 patients received BCG and 61 received Gem/Doce. Median age was 69 yr (interquartile range [IQR] 61-76) for the BCG group and 72 yr (IQR 62-76) for the Gem/Doce group. Median follow-up was 53.1 mo (IQR 25.3-71.2) for the BCG group and 20.2 mo (IQR 8.28-33.1) for the Gem/Doce group. The 2-yr high-grade RFS rates for primary high-grade tumors for BCG versus Gem/Doce groups were 81% versus 61%, with corresponding any-grade RFS rates of 60% versus 41%. Induction with Gem/Doce predicted any-grade recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.1-3.2) and high-grade recurrence for primary high-grade tumors (HR 3.4 95% CI 1.27-9.13), while receipt of maintenance therapy decreased the risk of any-grade recurrence (HR 0.4, 95% CI 0.22-0.72). This study is limited by its retrospective design.

Conclusions and clinical implications: For patients with IR-NMIBC, BCG was associated with superior any-grade RFS and high-grade RFS for primary high-grade tumors. Maintenance therapy was associated with better RFS when receiving Gem/Doce. Standardization and longer maintenance therapy protocols should be considered for Gem/Doce treatment.

Patient summary: We compared outcomes for patients who received two different in-bladder treatments for intermediate-risk bladder cancer. Bacillus Calmette-Guérin (BCG) led to better outcomes than gemcitabine + docetaxel (Gem/Doce). Monthly maintenance therapy improved recurrence-free survival for patients who received Gem/Doce. We conclude that maintenance therapy is essential for patients receiving Gem/Doce to avoid bladder cancer recurrence after treatment.

Background and objective: Understanding the learning curve for the da Vinci single-port (SP) surgical robot is crucial for adoption, training, and enhancement of surgical safety and efficiency. Our aim was to assess the impact of both overall experience (O-EXP) and procedure-specific experience (PS-EXP) on perioperative outcomes across various SP surgeries.

Methods: We analyzed data for 387 consecutive SP surgeries conducted by a high-volume surgeon from December 2018 to July 2023. These included SP robot-assisted radical prostatectomy (SP-RARP), robot-assisted simple prostatectomy (SP-RASP), and robot-assisted nephrectomy (SP-RANP). We used multivariable logistic regression to evaluate the relationship between surgeon experience and outcomes, and locally weighted scatterplot smoothing analysis to graphically explore the risk of postoperative complications according to O-EXP.

Key findings and limitations: The 387 SP procedures assessed included 172 (44%) SP-RARP, 53 (14%) SP-RASP, and 162 (42%) SP-RANP cases. Overall, 17% of patients had a complication of any grade, 6% experienced severe complications (Clavien-Dindo grade ≥3), and 8% required readmission. Both O-EXP and PS-EXP were associated with a lower risk of complications. The odds ratios for the incidence of complications per increment of 10 procedures were 0.83 (95% confidence interval [CI] 0.76-0.89) for PS-EXP and 0.93 (95% CI 0.90-0.96) for O-EXP. PS-EXP was also associated with a shorter operative time (β = -3.9, 95% CI -4.9 to -2.9). The risk of complications reached a minimum at 30 SP-RASP, 70 SP-RANP, and 150 SP-RARP cases. Our study is limited by its retrospective design, single-surgeon experience, and lack of functional outcome assessment.

Conclusions and clinical implications: Robot-assisted surgery with the da Vinci SP robot has a distinctive learning curve that is influenced by the platform and procedure-specific characteristics. For surgeons new to SP surgery, RASP and renal procedures had the earliest learning curve success and should be approached first, with RARP attempted only when the surgeon has become accustomed to the SP platform.

Patient summary: We investigated the learning curve for a surgical robot that uses just one keyhole incision. We found that the time to reach proficiency for urological surgeries with this specific robot, measured as the rate of complications, is faster for some procedures than for more complex operations. This information can help in improving surgeon training and patient safety.

Background and objective: Robotic adrenalectomy (RA) has attracted interest as an alternative to laparoscopic adrenalectomy (LA) for patients with pheochromocytoma, although its beneficial effects are uncertain. Our aim was to compare RA and LA outcomes for these patients.

Methods: Data for patients who underwent RA or LA for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed. We analyzed baseline characteristics and postoperative complications at discharge, 90 d, and 1 yr. We conducted propensity score matching (PSM; 1:1 ratio) and multivariable analyses to evaluate outcomes and risk factors for the occurrence of complications and higher Comprehensive Complication Index (CCI).

Key findings and limitations: Of 1755 patients, 1613 (91.9%) underwent LA and 142 (8.1%) underwent RA. Estimated blood loss, conversion rate, complication rate, and CCI at discharge, 90 d, and 1 yr were similar between the groups. However, RA was associated with a longer operative time in comparison to LA (100 vs 123 min; p < 0.001), but not after PSM (p = 0.120). Multivariable analysis revealed that Charlson comorbidity index (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.29; p = 0.001), and tumor size per 1-cm increment (OR 1.13, 95% CI 1.07-1.21; p < 0.001) were independently associated with the incidence of complications, but there was no significant difference in complication rates between the LA and RA groups (OR 1.09, 95% CI 0.63-1.87; p = 0.767). After PSM, RA was associated with a lower rate of severe (grade ≥3a) complications in comparison to LA (p = 0.023).

Conclusions and clinical implications: RA is a safe alternative to LA and yields similar outcomes for patients with pheochromocytoma. RA may be associated with a lower likelihood of severe complications. Further studies are warranted to determine the role of robotic surgery in pheochromocytoma.

Patient summary: Pheochromocytoma is a rare tumor in the adrenal gland and the gold-standard treatment is surgical removal. We assessed patient outcomes after robot-assisted surgery compared with laparoscopic surgery and found that outcomes are similar, but the rate of severe complications may be lower if a surgical robot is used.

Background and objective: Bladder cancer (BLCa) remains a prevalent malignancy with high recurrence rates and limited treatment options. In recent years, patient-derived organoids (PDOs) have emerged as a promising platform for studying cancer biology and therapeutic responses in a personalized manner. Using drug screening, PDOs facilitate the identification of novel therapeutic agents and translational treatment strategies. Moreover, their ability to model patient-specific responses to treatments holds promise for predicting clinical outcomes and guiding treatment decisions. This exploratory review aims to investigate the potential of PDOs in advancing BLCa research and treatment, with an emphasis on translational clinical approaches. Furthermore, we analyze the feasibility of deriving PDOs from minimally invasive blood and urine samples.

Methods: In addition to exploring hypothetical applications of PDOs for predicting patient outcomes and their ability to model different stages of BLCa, we conducted a comprehensive PubMed search on already published data as well as comprehensive screening of currently ongoing trials implementing PDOs in precision medicine in cancer patients irrespective of the tumor entity.

Key findings and limitations: While the research on BLCa PDOs is advancing rapidly, data on both BLCa PDO research and their clinical application are scarce. Owing to this fact, a narrative review format was chosen for this publication.

Conclusions and clinical implications: BLCa PDOs have the potential to influence the domain of precision medicine and enhance personalized cancer treatment strategies. However, standardized protocols for PDO generation, their ideal clinical application, as well as their impact on outcomes remain to be determined.

Patient summary: In this review, we discuss the current state and future needs for the use of patient-derived organoids, small three-dimensional avatars of tumor cells, in bladder cancer. Patient-derived bladder cancer organoids offer a more personalized approach to studying and treating bladder cancer, providing a model that closely resembles the patient's own tumor. These organoids can help researchers identify new treatment options and predict how individual patients may respond to standard therapies. By using minimally invasive samples such as blood and urine, patients can participate in research studies more easily, potentially leading to improved outcomes in bladder cancer treatment.