Urologic Oncology-seminars and Original Investigations最新文献

Background and objective: While some patients with metastatic renal cell carcinoma (mRCC) may experience an indolent disease progression and could benefit from deferred systemic therapy (ST), including active surveillance (AS) or metastasis-directed therapy (MDT), the evidence on its oncological efficacy and safety are still not well-established. We aimed to provide an overview of the available evidence on oncological outcomes of patients with mRCC undergoing deferred ST.

Methods: A systematic review of the literature was conducted in August 2024 using the PubMed, Scopus, and Embase databases to identify prospective and retrospective studies evaluating AS or deferred ST for patients with mRCC (PROSPERO ID: CRD42024579021). The co-primary outcomes were ST-free survival (ST-FS) and overall survival (OS). A random-effects model was used for quantitative analysis.

Key findings and limitations: We identified 15 eligible studies including 2,912 patients. Of these, 4 were prospective (n = 589 patients) and 11 were retrospective (n = 2,323 patients). The estimated 1-, 2-, 3-, 4-, and 5-year ST-FS rates (n = 1,070) were 74%, 54%, 49%, 43%, and 37%, respectively. The estimated 1-, 2-, 3-, 4-, and 5-year OS rates (n = 2,872) were 96%, 89%, 80%, 71%, and 69%, respectively. Key limitations at a study-level included selection bias, unmeasured confounding, and variability across deferred ST/AS protocols, including the indications for metastasis-directed therapy. Moreover, most studies used tyrosine kinase inhibitors as ST. The proportion of patients receiving MDT, including metastasectomy or stereotactic body radiation therapy, ranged from 14 to 100%.

Conclusions and clinical implications: Deferring ST by AS or MDT was associated with favorable oncological outcomes in carefully-selected patients with mRCC, highlighting the potential value of this approach in the contemporary multidisciplinary management of mRCC. Considering the limitations of available evidence and the lack of data on the oncological efficacy and safety of deferred ST for mRCC in the immune-oncology era, our review calls for further research in this field.

Immune-related adverse events (irAEs) are commonly associated with immune checkpoint inhibitor (ICI) therapy. ICIs are recommended at various stages of bladder cancer treatment, and appropriate management of irAEs is important in improving long-term outcomes in bladder cancer. This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess irAEs associated with ICI therapy in bladder cancer. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and Epistemonikos from inception till January 2025. The references of the included studies, clinicaltrials.gov, annual meeting abstracts of ASCO and ESMO, and the WHO International Clinical Trials Registry Platform were also searched for additional studies. Phase II or III randomized controlled trials (RCTs) where one of the experimental arms consisted of atezolizumab, pembrolizumab, nivolumab, or avelumab monotherapy were included. A Random effects model was used to conduct the meta-analysis in R Statistical Software, version 4.3.3. From the initial 1,092 articles screened, 12 were included in the systematic review and meta-analysis, comprising a total of 7,333 patients. Hypothyroidism (RR: 5.87 (3.23, 10.67)), hyperthyroidism (RR: 11.05 (4.20, 29.03)), pruritus (RR: 4.95 (2.82, 8.70)), rash (RR: 2.92 (1.51, 5.64)), colitis (RR: 2.15 (1.11, 4.15)), pneumonitis (RR: 3.91 (2.18, 7.02)), and nephritis (RR: 4.97 (1.43, 17.33)) were found to be significant irAEs associated with ICI therapy. Bladder cancer patients treated with ICIs are at significant risk of irAEs. These events vary in severity, and appropriate management of these adverse events should be prioritized to improve quality of life.

Purpose: To analyze temporal trends in time intervals from hematuria diagnosis to urology evaluation and cystoscopy in patients with bladder cancer and identify opportunities for improved interventions.

Materials and methods: We identified 84,515 Medicare beneficiaries in the SEER-Medicare database diagnosed with bladder cancer between 2005 and 2019, with hematuria claims within 12 months prior to diagnosis and urology visits thereafter. The co-primary outcome was delay (>30 days) and severe delay (>60 days) from hematuria claim to urology visit. The secondary outcome was delay (>14 days) and severe delay (>30 days) from urology visit to cystoscopy. We used joinpoint regression and logistic regression analyses.

Results: Delays from hematuria claim to urology visit increased over time; the proportion of patients experiencing a delay of over 30 days rose from 30.8% in 2005 to 35.1% in 2016, (Annual Percent Change (APC) 0.89%, P = NS).This trend accelerated significantly after 2016, reaching 39.2% in 2019 (APC 3.68%, P < 0.001). Females faced higher rates of delays throughout the study period. Females were 1.40 times more likely to experience a delay in their urology visit than males (aOR 1.40, 95% CI 1.34-1.46). Other variables associated with delay included Black and Hispanic race/ethnicity, not married, higher Charlson score, and residence. A preexisting relationship with a urologist reduced the delay likelihood (aOR 0.83, 95% CI 0.79-0.87).

Conclusions: Female patients continue to experience a disproportionately delayed urologic referral which has, unfortunately. worsened over time. To ensure equitable and timely diagnosis of bladder cancer, future interventions must focus on streamlining the initial referral process.

Purpose: The use of intraoperative diagnostic during ureterorenoscopy (URS) for upper tract urothelial cancer (UTUC) may assist in deciding between kidney-sparing or radical surgical approaches. We assessed the diagnostic performance of confocal microscopy (CM) using the Vivascope CM system compared to conventional histopathology.

Methods: This prospective feasibility cohort study included patients undergoing URS for suspected UTUC or during UTUC follow-up between May and August 2022. Each biopsy was analyzed first with the Vivascope CM, followed by conventional histopathology. The primary outcome was the UTUC detection rate with the VivaScope CM and conventional histopathological analysis, considering conventional analysis as the gold standard. Concordance between Vivascope CM and conventional histopathology in terms of high-grade UTUC was reported in terms of raw numbers and proportions. Analyses were conducted per biopsy sample and per patient.

Results: Ten patients underwent URS, with a total of fourteen biopsy samples. Suspicion of UTUC emerged in four (28.6%) cases because of hematuria and in four (28.6%) cases by CT-scan, while the remaining 6 cases (42.9%) underwent URS during the follow-up for UTUC. Per-biopsy analysis showed a cancer detection rate of 70% using Vivascope CM and a high-grade concordance of 50%. Among 5 CM high-grade cases, 2 were downgraded; 1 low-grade case was upgraded by conventional histopathology. Per-patient analysis showed a cancer detection rate of 77.8% using Vivascope CM and a high-grade concordance of 66.7%. Among 5 high-grade patients classified by CM, one was downgraded by conventional analysis, while one low-grade case was upgraded by conventional analysis. Vivascope CM produced artifacts that prevented histological analysis in 2 cases. The main limitation of current study is the low sample size.

Conclusions: VivaScope CM shows promise as an intraoperative tool for UTUC detection during URS. However, its performance in terms of tumor grading was limited in this preliminary experience. Larger, blinded studies, preferably including multiple biopsies per UTUC lesion, are needed to confirm the diagnostic accuracy of VivaScope CM and better define its potential role in clinical decision-making during URS.

Background and objective: Accurate prediction of recurrence and progression risk in non-muscle invasive bladder cancer (NMIBC) is essential for patient counseling and risk-adapted management. However, conventional models fail to account for the decrease in baseline risk over time. We therefore examined the conditional survival free of recurrence and progression in older adults with NMIBC to develop a dynamic risk prediction model.

Methods: We identified patients 66 to 89 years with Ta/Tis/T1 cN0 cM0 urothelial bladder cancer treated with transurethral resection of bladder tumor (TURBT) between 2000 and 2017 in SEER-Medicare. Conditional recurrence-free (RFS) and progression-free (PFS) survival were estimated using the Kaplan-Meier method. The associations of baseline characteristics with RFS and PFS at prespecified landmark times were evaluated using Cox-proportional hazards models.

Key findings and limitations: A total of 39,862 patients were included. Of these, 26,339 (66%) had Ta, 11,758 (29%) had T1, and 1,765 (4%) had Tis-disease. Median follow-up was 65 months. The 60-month RFS and PFS increased from 0.39 and 0.85 at baseline to 0.73 and 0.89 at 24-months event-free survival. Conditional RFS rapidly improved within the first 24 months before plateauing. Patients with T1-disease demonstrated the greatest improvement in conditional RFS. On multivariable analyses, T stage and tumor grade were less predictive of RFS with longer landmark times. Limitations include measurement error and risk heterogeneity within grade and stage subgroups.

Conclusions and clinical implications: Among patients with NMIBC, recurrence and progression risks decrease with longer event-free intervals, particularly among patients at highest risk of each event as reflected by tumor stage and grade. A dynamic risk prediction model can improve patient counseling and support risk-adapted management during follow-up.

Objective: The tryptophan-kynurenine (TRP-KYN) pathway, regulated by indoleamine 2,3-dioxygenase 1 (IDO1), plays a pivotal role in tumor immune escape. Altered TRP catabolism and IDO1 gene polymorphisms may influence bladder cancer (BC) behavior through immune metabolic mechanisms. To evaluate the diagnostic and prognostic value of plasma and urinary KYN/TRP ratios and the IDO1 rs10089084 (G > C) polymorphism in patients with BC.

Methods: In this case-control study, plasma and urine samples were obtained from 58 patients with BC and 70 healthy controls before diagnostic cystoscopy. TRP and KYN levels were quantified by high-performance liquid chromatography. IDO1 rs10089084 genotypes were determined via PCR-RFLP. Diagnostic accuracy was assessed by ROC analysis, and recurrence risk was analyzed using Cox regression.

Results: Plasma KYN/TRP ratios were significantly higher in BC patients than in controls (P = 0.011; AUC = 0.617). Among BC cases, the urinary KYN/TRP ratio discriminated patients with a visible bladder mass (AUC = 0.879; 95% CI 0.774-0.984; cut-off = 0.0895; sensitivity = 100%; specificity = 70.8%). In recurrence analysis, the IDO1 rs10089084 C allele independently predicted recurrence risk (HR = 7.51; 95% CI 1.70-33.10; P = 0.008). No association was found with progression.

Conclusions: Combined metabolic and genetic profiling implicates the IDO1-TRP-KYN axis in BC pathophysiology. Urinary KYN/TRP ratio offers a noninvasive, biologically grounded marker for intravesical tumor activity, while the IDO1 rs10089084 variant provides complementary prognostic information. These findings support the integration of immunometabolic biomarkers into risk-adapted surveillance strategies.