Urologic Oncology-seminars and Original Investigations最新文献

Background: The role of primary tumor ablation (pTA) in metastatic renal cell carcinoma (mRCC) is unknown. We compared pTA-treated mRCC patients to patients who underwent no local treatment (NLT), as well as patients who underwent cytoreductive nephrectomy (CN).

Methods: Within the Surveillance, Epidemiology, and End Results database (SEER, 2004-2020), we identified mRCC patients who underwent either pTA, NLT or CN. Endpoints consisted of overall survival (OM) and other-cause mortality (OCM). Propensity score 1:1 matching (PSM), multivariable cox regression models (OM), as well as, multivariable competing risk regressions (CRR) models (OCM) were used.

Results: We identified 27,087 mRCC patients, of whom 82 (0.3%) underwent pTA, 17,266 (64%) NLT and 9,739 (36%) CN. In comparisons of pTA vs. NLT mRCC patients addressing OM, after 1:1 PSM, median survival was 19 months for pTA vs. 4 months for NLT patients (multivariable HR 0.3, 95% CI 0.22-0.47, P < 0.001). No statistically significant OCM differences were recorded in multivariable CRR (HR 1.13 95%, CI 0.52-2.44, P = 0.8). In comparisons of pTA vs. CN, after 1:1 PSM, no statistically significant differences in OM (HR 1.22, 95% CI 0.81-1.83, P = 0.32), as well as OCM (HR 1.4, 95% CI 0.56-3.48, P = 0.5) were recorded.

Conclusion: In mRCC patients, pTA is associated with significantly lower mortality compared to NLT. Interestingly, OM rates between pTA and CN mRCC patients do not exhibit statistically significant differences. This preliminary report may suggest that pTA may provide a comparable survival benefit to CN in highly selected mRCC patients.

Purpose: Combination systemic therapies (CSTs) of immuno-oncologic (IO) and VEGF-inhibiting agents (VEGFi) have become the standard of care for management of metastatic clear cell renal cell carcinoma (m-ccRCC). However, treatment outcomes vary between patients, with no established biomarkers to determine optimal CST regimens (IO/IO or IO/VEGFi). Prostate Specific Membrane Antigen (PSMA), encoded by the FOLH1 gene, is a marker of tumor neovasculature in ccRCC, the downstream target of VEGFi. We evaluated the relation between FOLH1 expression and angiogenesis, as well as clinical outcomes, in 5 m-ccRCC ST trials.

Materials and methods: using Spearman's rank correlation (SPRC) test, we assessed the correlation between FOLH1 expression and gene expression signature (GES) scores corresponding to angiogenic and immunologic features of the tumor microenvironment (TME) of m-ccRCC in our trial cohorts. Using Cox proportional hazard regression (Cox-PHR), we assessed the association between FOLH1 expression level, summarized by within-study quantiles (qFOLH1), and progression-free and overall survival (PFS, OS).

Results: Increased FOLH1 expression was significantly associated with higher TME angiogenesis GES scores (SPRC +0.5, P < 0.001), but did not consistently correlate with immune feature GES scores. Meta-analysis of PFS in the sunitinib TKI arm of trial cohorts showed an overall positive association with qFOLH1 (HR = 0.89; 95% CI = 0.85-0.94, P < 0.0001). qFOLH1 was not significantly associated with OS in the sunitinib arms of the two trials with OS data (COMPARZ, HR 0.87, 95% CI 0.71-1.07, P = 0.17; and Checkmate-214, HR 0.89, 95% CI 0.67-1.17, P = 0.70).

Conclusions: PSMA-encoding FOLH1 gene expression correlates with neoangiogenesis and predicts PFS in m-ccRCC patients treated with sunitinib TKI, suggesting that PSMA PET could be explored as a noninvasive biomarker for guiding CST choice (IO/IO or IO/VEGFi) as well as prediction of treatment response to VEGFi in m-ccRCC patients.

Background: The standard treatment for non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is complete surgical resection; however, this procedure is complex and carries high complication rates and perioperative mortality. Previous studies have explored preoperative multimodal therapy to reduce surgical difficulty, but limited evidence prevents guideline recommendations. This study aimed to investigate the impact of neoadjuvant therapy on the prognosis of patients with RCC and IVC thrombus without distant metastasis.

Methods: Data from 2006 to 2024 on RCC patients with IVC thrombus undergoing radical nephrectomy plus IVC thrombus resection were collected. Patients received neoadjuvant therapy, including tyrosine kinase inhibitors or immune checkpoint inhibitors, followed by surgery. Tumor size and thrombus height were assessed by computed tomography. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier curves. Multivariate analysis was used to identify factors predicting DFS.

Results: Thirty-one patients who did not receive neoadjuvant chemotherapy therapy (NAC-Naive group) and 19 patients who received neoadjuvant chemotherapy therapy (NAC group) were analyzed. The NAC group showed significant reductions in primary renal tumor size and neutrophil-to-lymphocyte ratio compared to the NAC-Naive group just before nephrectomy. The NAC group had significantly improved DFS and OS. Median DFS and OS were not reached in the NAC group compared to 26.3 months and 73.5 months, respectively, in the NAC-Naive group. The NAC group had a 2-year recurrence-free survival rate of 70.9% compared to 50.6% in the NAC-Naive group. Multivariate analysis identified a preoperative tumor size of 10 cm or larger and lack of neoadjuvant therapy as poor prognostic factors for DFS.

Conclusion: Neoadjuvant therapy significantly improves the prognosis of RCC patients with IVC thrombus. This therapy reduces surgical invasiveness and has a mid- to long-term preventive effect on recurrence. These findings support the potential benefit of neoadjuvant systemic therapy in improving outcomes for this patient population.

Objectives: We aimed to investigate the prognostic significance of tumor size in metastatic renal cell carcinoma (mRCC) by comparing the effectiveness of dual immune checkpoint inhibitor (IOIO) and immune checkpoint inhibitor combined with tyrosine kinase inhibitor (IOTKI) therapies.

Methods: This retrospective observational study included patients with mRCC diagnosed between October 2014 and February 2024 who received IOIO or IOTKI treatment at Kobe University Hospital and 5 affiliated hospitals. Clinical and imaging data were collected, and target lesions were measured according to RECIST v.1.1 criteria. Time-dependent ROC curve analysis was performed to evaluate the prognostic value of tumor size, nephrectomy status, and IMDC risk criteria for progression-free survival (PFS) and overall survival (OS).

Results: The study included 180 mRCC patients, consisting of 99 receiving IOIO therapy and 81 receiving IOTKI therapy. Time-dependent AUC analysis showed that tumor size had a higher predictive ability for PFS and OS in the IOIO group than the IOTKI group. In multivariate analysis, tumor size was a significant independent prognostic factor for PFS (HR: 1.010, 95% CI: 1.004-1.016, P < 0.001) in the IOIO group. Moreover, the AUC for tumor size was consistently superior in predicting outcomes compared to nephrectomy status and IMDC risk classification in the IOIO group. Kaplan-Meier curves indicated that tumor size effectively stratified PFS in both nephrectomized and non-nephrectomized cases.

Conclusion: Tumor size significantly impacts the prognosis of mRCC patients treated with IOIO therapy, demonstrating greater predictive ability than nephrectomy status and IMDC risk classification. These findings suggest that tumor volume should be considered a critical factor in treatment decision-making for renal cancer, particularly in patients undergoing IOIO therapy.

Objective: Renal Tumor biopsy (RTB) can assist clinicians in determining the most suitable approach for treatment of renal cancer. However, RTB's limitations in accurately determining histology and grading have hindered its broader adoption and data on the concordance rate between RTB results and final pathology after surgery are unavailable. Therefore, we aimed to develop a machine learning algorithm to optimize RTB technique and to investigate the degree of concordance between RTB and surgical pathology reports.

Materials and methods: Within a prospectively maintained database, patients with indeterminate renal masses who underwent RTB at a single tertiary center were identified. We recorded and analyzed the approach (US vs. CT), the number of biopsy cores (NoC), and total core tissue length (LoC) to evaluate their impact on diagnostic outcomes. The K-Nearest Neighbors (KNN), a non-parametric supervised machine learning model, predicted the probability of obtaining pathological characterization and grading. In surgical patients, final pathology reports were compared with RTB results.

Results: Overall, 197 patients underwent RTB. Overall, 89.8% (n=177) and 44.7% (n=88) of biopsies were informative in terms of histology and grading, respectively. The discrepancy rate between the pathology results from renal tissue biopsy (RTB) and the final pathology report following surgery was 3.6% (n=7) for histology and 5.0% (n=10) for grading. According to the machine learning model, a minimum of 2 cores providing at least 0.8 cm of total tissue should be obtained to achieve the best accuracy in characterizing the cancer. Alternatively, in cases of RTB with more than two cores, no specific minimum tissue threshold is required.

Conclusions: The discordance rates between RTB pathology and final surgical pathology are notably minimal. We defined an optimal renal biopsy strategy based on at least 2 cores and at least 0.8 cm of tissue or at least 3 cores and no minimum tissue threshold.

Patients summary: RTB is a useful test for kidney cancer, but it's not always perfect. Our study shows that it usually matches up well with what doctors find during surgery. Using machine learning can make RTB even better by helping doctors know how many samples to take. This helps doctors treat kidney cancer more accurately.

Aims: The aim of the study was to analyze the cut-off value for the percentage of the high-grade (HG) component that has clinical significance in urothelial carcinoma (UC).

Material and methods: The study included a total of 362 patients, mixed-grade UC (MGUC) patients were classified as Combine Group (CG) 1 based on the presence of less than 5% HG areas. High-grade papillary UC (HGPUC) patients were grouped based on HG component proportions: CG2 (≥5%-<50% HG), CG3 (≥50%-<100% HG), and pure HGPUC (PHGPUC) for 100% HG components.

Results: There was a statistically significant difference between low-grade papillary UC (LGPUC) and CG1, CG2, or CG3, as well as LGPUC and PHGPUC, in terms of cancer-specific survival (CSS) (hazard ratio (HR) = 19.85, 95% confidence interval (CI) = 2.30-171.10 P = 0.007, HR = 28.38, 95% CI = 3.50-229.97 P = 0.002, HR = 18.64, 95% CI = 2.26-153.64 P = 0.007, and HR = 35.41, 95% CI = 4.61-271.72 P < 0.001, respectively). There was no statistically significant difference between PHGPUC and CG1, CG2, or CG3 in terms of CSS.

Conclusions: These findings suggest that even the presence of less than 5% HGPUC within LGPUC significantly impacts CSS. Furthermore, the increase in the percentage of HGPUC beyond 5% does not substantially influence the CSS. Based on these findings, disclosing the percentage of the high-grade component may be crucial for future patient management and treatment.

Modern advances in systemic and localized therapies for patients with renal cell carcinoma (RCC) have significantly improved patients' outcomes. If disease progression occurs after initial treatment, clinicians often have multiple options for a first salvage therapy. Because salvage and initial treatments both may affect overall survival time, and they may interact in unanticipated ways, there is a growing need to determine sequences of initial therapy and first salvage therapy that maximize overall survival while maintaining quality of life. The complexity of this problem grows if a second salvage therapy must be chosen for patients with treatment-resistant disease or a second progression occurs following first salvage. On November 9, 2023, a think tank was convened during the International Kidney Cancer Symposium (IKCS) North America to discuss challenges in accounting for postprogression therapies when estimating overall survival (OS) time based on randomized controlled trial (RCT) data. The present manuscript summarizes the topics discussed, with the aim to encourage adoption of statistical methods that account for salvage therapy effects to obtain scientifically valid OS estimation. We highlight limitations of traditional methods for estimating OS that account for initial treatments while ignoring salvage therapy effects and discuss advantages of applying more sophisticated statistical methods for estimation and trial design. These include identifying multistage treatment strategies, correcting for confounding due to salvage therapy effects, and conducting Sequentially Multiple Assignment Randomized Trials (SMARTs) to obtain unbiased comparisons between multistage strategies. We emphasize the critical role of patient input in trial design, and the potential for information technology (IT) advances to support complex trial designs and real-time data analyses. By addressing these challenges, future RCTs can better inform clinical decision-making and improve patient outcomes in RCC.

Background: Recent studies have underscored a potential link between gut microbiota and urological tumors, yet the causal relationship with bladder cancer (BCa) and the role of metabolic pathways remain unclear.

Methods: Instrumental variables (IVs) for gut microbiota were obtained from genome-wide association studies (GWAS) conducted by the MiBioGen consortium (n = 18,340). GWAS data for BCa were sourced from a comprehensive genome-wide meta-analysis encompassing 23 cohorts. Mendelian randomization (MR) was employed to investigate the causal relationship between gut microbiota and BCa, utilizing inverse variance weighted (IVW) as the primary MR method. Additionally, metabolic pathways associated with these microbiota were analyzed to understand their functional roles in BCa pathogenesis. Sensitivity analyses were conducted to validate all MR results.

Results: The MR analysis identified five gut microbiota taxa with a causal association with BCa, with the genus Bilophila notably promoting BCa. Metabolic pathway analysis revealed significant associations between specific pathways and BCa, suggesting that changes in amino acid and NAD metabolism might influence BCa development. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy among the IVs.

Conclusion: This study revealed the significant causal relationship between gut microbiota and BCa, particularly identifying Bilophila as a key pathogenic initiator. These findings elucidated the potential impact of metabolic pathways, especially amino acid and NAD metabolism, on the pathogenesis of BCa. They not only laid the foundation for innovative therapeutic strategies but also highlighted the immense potential of microbiota-based interventions in the prevention and treatment of BCa, paving the way for new directions in precision medicine.

Purpose: The availability of targeted therapies for advanced prostate cancer led to the expansion of national guidelines recommending germline genetic testing. The aim of this study was to describe recent trends in germline test ordering patterns for patients with prostate cancer.

Materials and methods: A retrospective cohort analysis of patients with prostate cancer who underwent germline testing through a single commercial laboratory (Invitae Corporation) between 2015-2020 was performed. Ordering trends between provider medical specialties were compared. Our primary hypothesis was that the proportion of tests ordered by urologists would increase over time.

Results: In total, 17,256 prostate cancer patients underwent germline genetic testing; 14,400 patients had an ordering provider with an associated medical specialty and were included in the final comparison cohort. Total prostate cancer patients undergoing germline testing increased quarterly from 21 in Q2 of 2015 to 1,509 in Q3 of 2020. The proportion of tests ordered by urologists increased from 0% in Q2 2015 to 8.3% in Q3 2020 (P < 0.001). Compared to medical genetics, medical oncology, and other specialties, urology ordered more tests for patients under 70 years old (66% vs 51%-55%, P <0.004) and for patients who reported negative family history (25% vs 12%-20%, P = 0.012).

Conclusions: As awareness and indications for germline testing continue to expand, aggregate ordering volume is increasing, and urologists are becoming more involved in facilitating testing. This highlights the continued importance of educating urologists on the indications for and implications of germline genetic testing, as well as providing tools to support implementation.