Urologic Oncology-seminars and Original Investigations最新文献

Objective: Demographic changes will lead to higher proportions of metastatic hormone-sensitive (mHSPC) and castration resistant metastatic prostate cancer (mCRPC) patients with higher frailty index and multiple comorbidities.

Materials and methods: We relied on an institutional tertiary-care database to explore the effect of frailty (Eastern Cooperative Oncology Group [ECOG]), as well as cardiovascular (CVD) and secondary malignancy (SecCa) comorbidities on overall survival (OS) and time to mCRPC in mHSPC and OS in mCRPC patients with Kaplan-Meyer estimates and Cox regression models.

Results: Of 802 mHSPC patients, 61% were ECOG0 vs. 32% ECOG1 vs. 6.5% ECOG≥2. Significant differences in baseline patient and baseline mHSPC characteristics were observed for all three groups (all P ≤ 0.05). In time to mCRPC analyses and OS analyses of mHSPC and mCRPC patients, significant disadvantages were observed for ECOG 1/≥2 patients, relative to ECOG0, even after multivariable adjustment. Moreover, 31% of included patients had history/active CVD, which yielded significant median OS differences in mHSPC patients (95 vs. 63 months, multivariable hazard ratio: HR: 1.77, P < 0.01), but not in mCRPC patients (P = 0.085). After stratification according to SecCa, 14% had a SecCa which led to significant median OS differences in mCRPC patients (50 vs. 37 months, P < 0.01) but not in mHSPC patients (76 vs. 64 months, P = 0.089). Patients with higher frailty index and comorbidities showed significant differences in therapy lines.

Conclusion: Frailty and specific comorbidities significantly influence cancer-control outcomes in mHSPC, as well as mCRPC patients, even after controlling for adverse tumor characteristics.

Purpose: To investigate the association of diabetes mellitus and metformin use with metabolic acidosis risk after radical cystectomy (RC) and urinary diversion for bladder cancer.

Materials and methods: This retrospective cohort study used TriNetX Research Network data. Patients undergoing RC with continent diversion or ileal conduit for bladder cancer were identified using International Classification of Diseases, 10th Revision (ICD-10) and ICD-10 Procedure Coding System (ICD-10-PCS) codes. The primary outcome was acidosis between 1 month and 3 years postsurgery. Risk ratios (RR) and odds ratios (OR) were calculated based on diabetes and metformin use, stratified by diversion type and chronic kidney disease stage. Propensity score matching balanced potential confounders.

Results: We identified 1,986 patients who underwent continent diversion and 11,184 who underwent ileal conduit reconstruction. In matched analyses, diabetes patients had higher acidosis risk (continent diversion: RR 1.87, 95% confidence interval [CI] 1.39-2.51; ileal conduit: RR 1.94, 95% CI 1.66-2.27). The risk was highest for diabetes patients with metformin prescription (continent diversion: RR 2.06, 95% CI 1.63-2.61; ileal conduit: RR 2.13, 95% CI 1.84-2.47). However, among patients with diabetes, metformin use did not significantly affect acidosis rates in most analyses. Continent diversion patients had higher acidosis risk than ileal conduit patients (RR 1.89, 95% CI 1.58-2.26).

Conclusion: Diabetes significantly increases metabolic acidosis risk after RC with urinary diversion, especially in continent diversion patients. While metformin may contribute to metabolic acidosis risk, its impact appears less significant than that of diabetes. Careful monitoring and appropriate metformin adjustments are crucial in this population.

Objectives: To evaluate the concordance between the intraoperative visual assessment of the tumor bed for completeness of resection following partial nephrectomy and the permanent section analysis of biopsies taken from the tumor bed.

Methods: Patients undergoing partial nephrectomy at 2 university hospitals were prospectively enrolled. R.E.N.A.L. nephrometry score of tumors were calculated according to preoperative imaging. Masses were resected either by enucleation or with a safety margin. To ensure accurate excisional biopsy from the entire tumor bed, all resections were performed using the open technique. After tumor excision and confirmation of complete resection through gross inspection, 4 samples-1 from each quadrant of the tumor bed-were taken and sent for permanent section analysis. The concordance between the surgeons' visual inspection and final pathological analysis was then evaluated RESULTS: A total of 52 partial nephrectomies were included in this study. The mean tumor size was 49.5±22.6mm with a mean R.E.N.A.L nephrometry score of 7.13±1.93. Masses were removed by enucleation in 21 cases (40.4%) and with a safety margin in 31 cases (59.6%). Nine masses (17.3%) were benign, and 43 (82.7%) were renal cell carcinomas. None of the tumor bed biopsies were positive, indicating 100% concordance between the surgeons' visual inspection and the final pathological analysis.

Conclusion: Our findings suggest that the surgeons' macroscopic evaluation of the tumor bed during partial nephrectomy is a reliable method for confirming complete resection. Performing biopsies from the tumor bed to confirm negative margins does not appear to provide additional diagnostic value.

Purpose: UGN-101, a reverse thermal mitomycin gel for upper tract instillation, recently became the first FDA approved treatment for upper tract urothelial carcinoma (UTUC). However, the durability of UGN-101 treatment has not been well described. Here we present long term outcomes from our multi-institutional cohort for patients who initially responded to treatment.

Materials and methods: We identified patients from a multi-institutional database with UTUC who had a negative endoscopic evaluation following either adjuvant or chemoablative UGN-101 induction. Recurrence and progression data for those patients was reviewed. Kaplan-Meier survival analysis was performed, stratified by relevant clinical features.

Results: We identified 56 renal units that met the inclusion criteria of which 93% had low-grade disease while 4 cases had high-grade UTUC. With a median follow-up of 23.5 months, 21.4% of renal units experienced a recurrence, with 65% of renal units recurrence-free at 36 months. Three patients experienced eventual progression of disease leading to mortality, however only 1 of these patients had presumed low-grade UTUC and did not undergo nephroureterectomy on recurrence due to solitary kidney.

Conclusions: UGN-101 treatment has excellent durability in patients who initially respond to the treatment. Further study is needed to better understand the long term outcomes of this novel therapy and also the risks/benefits of maintenance therapy in this setting. Caution should be used in patients with high-grade disease who appear to be at higher risk of relapse and death despite initial response.

Purpose: Aimed to evaluate the prognostic value of Pan-Immune-Inflammation Value (PIV) for overall survival (OS) in the localized RCC. We also tested the feasibility of incorporating the PIV into UCLA Integrated Staging System (UISS).

Materials and methods: Retrospectively evaluated 197 consecutive ≥pT2a radical nephrectomy patients. PIV and other blood based inflammatory markers were calculated. The optimal cut-offs of inflammatory markers were determined. The C-index was calculated. Cox regression analyses were done.

Results: Median age and follow-up time were 59 yrs. and 49 mo., respectively. Two, 5 and 10 years OS was 81.4%, 69.4% and 45.6%. Age, BMI, anemia, lymph node positivity, UISS and all inflammatory markers were found to be significant predictive factors. However, PIV had the highest hazard ratio [HR: 2.39 (1.38-4.14)] and also had highest C-index contribution (+0.24%) in multivariable analyses. Furthermore, both UISS and PIV remained independent predictive factors (P = 0.027 and P = 0.002, respectively). Additionally, pre- and postoperative low PIV provided about half reduction in the risk of death [HR: 0.44 (0.24-0.81), P = 0.008].

Conclusions: PIV was found to be an independent predictive factor in localized RCC. When PIV was included to the model, both UISS and PIV remained significant predictors and also PIV increased the C-index of the model.

Introduction: To test for cancer specific mortality (CSM) differences after either radical prostatectomy (RP) or radiotherapy (RT) in incidental prostate cancer (IPCa) patients.

Patients and methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015), IPCa patients were identified. Cumulative incidence plots as well as competing risks regression (CRR) models were fitted to address CSM after adjustment for other-cause mortality (OCM). Furthermore, a subgroup analysis was performed to test for CSM differences between RP and RT according to Gleason sum (GS 6,7, and 8-10).

Results: Of 1,466 IPCa patients, 770 (53%) underwent RP vs. 696 (47%) RT. Incidental PCa RT patients were older, and exhibited higher PSA, higher proportion of Gleason sum 8-10, and higher clinical T stage. In cumulative incidence plots, 5-year CSM rates adjusted for OCM were 0.9 for RP vs. 6.8% for RT (Δ = 5.9%). After multivariable adjustment for clinical characteristics (age, PSA, Gleason sum, and clinical T stage) as well as for OCM, RP was associated with a protective hazard ratio (HR) of 0.35 (95% confidence interval [CI] 0.15 - 0.78, p value = .01). Within Gleason sum 8-10 IPCA patients, RP was associated with a protective HR of 0.31 (P = .039).

Conclusion: Incidental PCa RT-treated patients exhibited less favorable clinical characteristics than their RP counterparts. Despite full adjustment, RP was associated with a protective effect relative to RT. This effect exclusively applied to the Gleason sum 8-10 subgroup. In consequence, IPCa patients harboring Gleason sum 8-10 should ideally be considered for RP instead of RT.

A complex and often under-appreciated relationship exists between the human microbiome, diet, and the development or progression of cancer. There is likewise an emerging appreciation for the role that the human-associated microbiota play in mediating cancer treatment response. This seminar series covers our current understanding of the interplay between the microbiome and cancer in genitourinary malignancies inclusive of bladder, kidney, and prostate cancers.

Background: Prostate cancer treatment involves hormonal therapies that may carry cardiovascular risks, particularly for long-term use. Gonadotropin-releasing hormone (GnRH) antagonists, such as degarelix, may offer advantages over agonists, but comprehensive comparative cardiovascular outcomes are not well established. This study aimed to systematically review and analyze the cardiovascular safety profiles of degarelix compared to those of traditional GnRH agonists, providing critical insights for optimizing treatment strategies.

Methods: We used Medline (PubMed), Scopus, Embase, Cochrane, and Web of Science databases to identify included studies using a preferred search strategy. All studies assessed the cardiovascular events profile between degarelix versus GnRH agonists were included in our study. We used the review manager version 5.4 to perform the analysis.

Results: 13 studies (160,214 participants) were included in this meta-analysis. Degarelix was associated with a significantly lower incidence of major adverse cardiovascular events [RR: 0.60, 95%CI (0.41, 0.88), P value = .008]. Incidence of stroke [RR: 0.92, 95%CI (0.56, 1.50), P value= .74], hypertension [RR: 0.85, 95%CI (0.37, 1.93), P value= .69], myocardial infarction [RR: 0.82, 95%CI (0.55, 1.21), P value= .31], heart failure [RR: 0.88, 95%CI (0.63, 1.23), P value= .46] and arrhythmia [RR: 0.61, 95%CI (0.24, 1.54), P value= .30] did not reach a statistically significant difference between groups.

Conclusion: Degarelix demonstrates a lower incidence of major adverse cardiovascular events compared to GnRH agonists, suggesting a potential cardiovascular safety advantage in prostate cancer treatment. Further studies are required to prove the results of our systematic review and meta-analysis.

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer.

Background: Primary testicular lymphoma (PTL) is a rare malignancy whose epidemiology and prognosis have not been studied.

Materials and methods: PTL patient data were collected from the SEER online database, and the data were divided into a training cohort and a validation cohort according to random assignment. The training cohort was subjected to a one-way COX regression analysis, and statistically significant differences were included in the multi-factor COX regression analysis and constructed nomograms. Forest plots were constructed based on risk factors. The validity of the nomograms was verified by observing the C-index size of the nomograms, the percentage of area under the ROC curve, and the degree of fit of the prediction curve in the calibration plot. The validation cohort verified the accuracy and applicability of the nomograms.

Result: The patient's age, tumor histologic type, Ann Arbor stage, grade of differentiation, and whether or not they received radiation and chemotherapy were significantly associated with poor prognosis in PTL.

Conclusion: The nomogram constructed based on multivariate COX regression analysis can predict the prognosis of PTL patients. The online visualization nomogram can help clinicians calculate the survival rate of PTL tumor patients and conduct personalized prognostic assessments for PTL tumor patients.