Endoscopic intervention versus radical nephroureterectomy for the management of localized upper urinary tract urothelial carcinoma: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: Localized Upper Urinary Tract Urothelial Carcinoma (UTUC) is an uncommon cancer typically detected at an advanced stage. Currently, radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for high-risk UTUC. This meta-analysis aims to evaluate the 5-year overall and cancer-specific survival and bladder recurrence rates in studies comparing endoscopic kidney-sparing surgeries (E-KSS) with RNU in localized UTUC. EVIDENCE ACQUISITION: We performed a literature search on 20th April 2023 through PubMed, Web of Science, and Scopus. The PICOS model was used for study inclusion: P: adult patients with localized UTUC; I: E-KSS. C: RNU; O: primary: overall survival (OS); secondary: cancer-specific survival (CSS), bladder recurrence rate, and metastasis-free survival (MFS). S: retrospective, prospective, and randomized studies. EVIDENCE SYNTHESIS: Overall, 11 studies involving 2284 patients were eligible for this meta-analysis, 737 in the E-KSS group and 1547 in the RNU group. E-KSS showed a similar overall 5-year OS between E-KSS and RNU, and for low-grade tumors, while 5-year OS favored RNU for high-grade tumors (RR 1.84, 95% CI 1.26-2.69, p = 0.002). No difference emerged for 5-year CSS between the two groups, even when the results were stratified for low- and high grade tumors. Bladder recurrence rate and 5-year MFS were also similar between the two groups. CONCLUSIONS: Our review showed that E-KSS is a viable option for patients with localized UTUC with non-inferior oncological outcomes as compared with RNU, except for 5-year OS in high-grade tumors which favoured RNU.

The Role of 12/14F Ureteral Access Sheath in Flexible Ureteroscopy for Moderate Nephrolithiasis.

INTRODUCTION: The aim was a retrospective analysis of 12/14F ureteral access sheath (UAS) usage on perioperative outcomes in patients with moderate nephrolithiasis (MN). MN was defined as a maximum of two unilateral kidney stones with a maximum stone diameter of 6-10 mm. MATERIAL AND METHODS: We conducted a monocentric retrospective univariate and multivariate analysis of flexible ureteroscopies (fURS) performed for MN between 01/2014 and 12/2018. RESULTS: A total of 402 fURS were performed in patients with urolithiasis; 112 MN cases underwent further analysis. UAS was successfully applied in 33 MN cases [33/112 (29.46%)]. UAS was inserted regardless of the maximum kidney stone diameter and the presence of multiple kidney stones (p > 0.05). Univariate analysis revealed a prolonged median operation time (UAS: 94 min, non-UAS: 74 min, p = 0.04) and median fluoroscopy time (UAS: 75 s, non-UAS: 57.5 s, p = 0.04) in the UAS cohort. These differences were not confirmed on multivariate logistic regression.UAS was not associated with better stone-free rates in either the univariate or multivariate analysis (UAS: 26/33, non-UAS: 61/79, p = 1.0) nor with the occurrence of Clavien-Dindo ≥2 complications (UAS: 3/33, non-UAS: 9/79, p = 0.98) or median length of hospital stay (UAS: 2 days, non-UAS: 2 days, p = 0.169). CONCLUSION: We identified no statistical benefits from the usage of 12/14F UAS for MN. As no relevant UAS-associated complications were documented, both strategies (with and without UAS) are feasible.

Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis.

Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis enabling a risk-adapted disease management is still a major clinical challenge. Existing studies evaluating the prognostic potential of PSMA (prostate-specific membrane antigen) for PCa were performed on radical prostatectomy specimens (RPE), i.e., decision making for disease management was already completed at time of sample analysis. Aim of our study was to assess the prognostic value of PSMA expression for PCa patients on biopsies at time of initial diagnosis. Methods: PSMA expression was assessed by immunohistochemistry on 294 prostate biopsies with corresponding RPE, 621 primary tumor foci from 242 RPE, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases and 52 benign prostatic samples. PSMA expression was correlated with clinico-pathologic features. Primary endpoint was recurrence free survival. Other clinicopathologic features included WHO/ISUP grade groups, PSA serum level, TNM-stage, and R-status. Chi-square test, ANOVA-analyses, Cox-regression, and log-rank tests were performed for statistical analyses. Results: High PSMA expression on both biopsy and RPE significantly associates with a higher risk of disease recurrence following curative surgery. The 5-year-recurrence free survival rates were 88.2, 74.2, 67.7 and 26.8% for patients exhibiting no, low, medium, or high PSMA expression on biopsy, respectively. High PSMA expression on biopsy was significant in multivariate analysis predicting a 4-fold increased risk of disease recurrence independently from established prognostic markers. PSMA significantly increases during PCa progression. Conclusion: PSMA is an independent prognostic marker on biopsies at time of initial diagnosis and can predict disease recurrence following curative therapy for PCa. Our study proposes the application of the routinely used IHC marker PSMA for outcome prediction and decision making in risk-adapted PCa management on biopsies at time of initial diagnosis.

Interstitial lung disease during targeted therapy in metastatic renal cell carcinoma: a case series from three centres.

Interstitial lung disease (ILD) is an adverse event which occurs also during targeted treatment of patients with metastatic renal cell carcinoma (mRCC). Experiences on ILD-management in mRCC remain limited. mRCC patients treated with everolimus, temsirolimus, or sunitinib at three centres from January 2006 until December 2009 were analysed, retrospectively. Medical records and imaging studies, as well as clinical course, the incidence, diagnostic measures, treatment, and outcome of ILD were assessed. Twenty-six ILD patients (11 %) were identified out of 237 mRCC patients. Median treatment until ILD-diagnosis was 3.8 (range: 1-21.5) months. The ILD-frequency was 2.7 % (n = 6/226) during sunitinib therapy and 19.8 % (n = 20/101) during m-TOR-inhibitor treatment. Cough was the prevailing symptom (69.2 %, n = 18). Bronchoalveolar lavage reviled often lymphocytic (42.9 %, n = 6/14) or eosinophilic cellularity (28.6 %, n = 4/14). Dose reduction (42.3 %, n = 11), treatment interruption (46.2 %, n = 12) or termination (23.1 %, n = 6), and steroid application (34.6 %, n = 9) were common measures in ILD. Interestingly, eosinophilic ILD required pulsed steroids. Improvement occurred in 73.7 % of symptomatic patients. Continuation of targeted therapies was warranted in 65.4 % of ILD patients. No patient died from ILD. ILD during targeted mRCC treatment is common, and supportive measures should be adapted to the clinical course, and potentially in dependence of BAL findings. Re-exposure to targeted therapies appears feasible.

Enzalutamide after docetaxel and abiraterone therapy in metastatic castration-resistant prostate cancer.

INTRODUCTION: Enzalutamide is a novel antiandrogen which is approved for the treatment of metastatic, castration-resistant prostate cancer (mCRPC) after taxane-based chemotherapy. The efficacy of enzalutamide after the sequence docetaxel and abiraterone is not proven. METHODS: Thirty-five mCRPC patients in the German compassionate use program, who received enzalutamide after progression with taxane-based chemotherapy and abiraterone were prospectively evaluated. The endpoints of the study were overall survival, radiologic progression-free survival and safety. RESULTS: The median treatment duration on enzalutamide was 2.8 months. The median overall survival was 7.5 months [95% confidence interval (CI) 4.7-10.3] while median progression-free survival assessed by imaging was 3.1 months (95% CI 1.4-4.8). The most common toxicities of all grades were anemia and weight loss. CONCLUSION: Although the results are limited by a small patient number, the consecutive use of enzalutamide and abiraterone after taxane-based chemotherapy shows a modest clinical activity. Thus, sequence therapy alternating between chemotherapy and antihormonal drugs might be a more promising approach in mCRPC treatment.

The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors--is there more to come?

The field of renal cell carcinoma (RCC) treatment has changed dramatically during recent years. Sunitinib, sorafenib and pazopanib were the first generation of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) to have significant clinical activity in metastatic clear cell RCC. These TKI share inhibition of VEGFR family members, but differ in their ability to block other cellular kinases. Axitinib and tivozanib are 2nd generation TKIs, which show high specificity for VEGFR inhibition and exert a favourable toxicity profile. Both agents have succeeded in pivotal clinical trials, which were the first studies to compare two distinct TKIs. Progression free survival (PFS) shows an advantage for the 2nd generation TKIs, but also curbs enthusiasm for limitless PFS expectations with a PFS plateau of 13-14 months in 1st line treatment. More recently, novel targets have gained attention in RCC, such as the mesenchymal epithelial transition factor also known as the MET receptor and the fibroblast growth factor receptor (FGFR). These receptors are included into the inhibitory profiles of third generation TKIs such as cabozantinib or dovitinib, which showed promising activity in early clinical trials. Randomised controlled trials explore the role of these agents, and whether the expansion of targets inhibited may lead to more effective treatments in RCC.

Decreased galectin-8 is a strong marker for recurrence in urothelial carcinoma of the bladder.

OBJECTIVE: To investigate galectin-8 expression patterns in normal urothelium and bladder cancer specimens and to elucidate its prognostic value. MATERIALS AND METHODS: 162 samples of non-muscle-invasive transitional cell carcinoma, 25 samples of muscle-invasive transitional cell carcinoma and 10 samples of normal urothelium were investigated by immunohistochemistry using tissue microarrays. Complete patient and tumor characteristics were compared with galectin-8 staining patterns. The likelihood of tumor recurrence and progression was analyzed based on a 3-year follow-up. RESULTS: Loss of galectin-8 was associated with the likelihood of tumor recurrence in univariate (p < 0.05) and multivariate analyses (p < 0.01). No significance was observed for tumor progression. Patients whose specimens showed weak galectin-8 expression had a shorter recurrence-free interval (42 vs. 12 months; p < 0.01, log-rank test). All of the 10 normal urothelium samples showed high galectin-8 expression. Decreased staining was found to be associated with higher tumor stages and grades (p < 0.0001, one-way ANOVA). A significant difference was found comparing normal urothelium with any tumor stage (p < 0.01), pTa vs. pT1 tumors (p < 0.05) and non-muscle-invasive vs. muscle-invasive tumors (p < 0.0001). CONCLUSIONS: Loss of galectin-8 might be an early step in the development of malignant lesions of the bladder and is a significant independent predictor of recurrence.

Decreased expression of galectin-3 predicts tumour recurrence in pTa bladder cancer.

Galectin-3 (gal-3) is a glycoprotein involved in various physiological cellular processes. Altered expression/loss of function of gal-3 is suggested to be involved in the pathogenesis and further progression of various human cancer entities. The aim of the present investigation was to elucidate the role of galectin-3 in the development and/or progression of non-muscle invasive (pTa, pT1) transitional cell carcinoma (TCC) of the urinary bladder. Gal-3 was analyzed by immunohistochemistry in 162 randomly selected non-muscle invasive bladder cancer specimens (pTa, 91; pT1, 71) using tissue microarray technique. It was compared with various patient and tumour characteristics (t-test). In addition, the role of gal-3 in association with tumour recurrence and progression was investigated (Log-rank test, Cox regression analysis). Gal-3 was found to be negatively correlated with tumour grade (p<0.02). Within the group of non-muscle invasive TCC, gal-3 could not differentiate between pTa and pT1 tumours (p=0.50), and within the subgroup of pTa tumours, loss of gal-3 determined the likelihood for the development of recurrent disease (p<0.03; Student's t-test). Furthermore, as demonstrated by Kaplan-Meier analysis, the expression level of gal-3 was identified to predict the duration of recurrence-free survival (p=0.01). In the multivariate analysis, gal-3 was found as an independent prognostic marker for predicting recurrence among the cohort of bladder tumours classified as pTa. In conclusion, loss of galectin-3 appears to be involved in the carcinogenesis of TCC and to serve as a valuable biological variable to identify a subgroup of Ta bladder cancer patients at high risk for the development of recurrent disease.

Intracranial aspergillosis in a non-immunocompromised patient treated for muscle-invasive bladder cancer.

We report a case of intracerebral Aspergillosis in a patient undergoing radical cystectomy for the treatment of muscle-invasive bladder cancer who did not reveal any deterioration of the immune system. Aspergillus fumigatus is an ubiquitously present, airborne fungus that tends to infect the upper respiratory tract. However, the latter was not observed in the patient presented. Complications in the form of an involvement of the central nervous system are very rarely recognized as a result of an Aspergillus infection and primarily occur in patients who are not immunologically competent. To our knowledge, we present the first case of intracerebral invasive Aspergillosis in an otherwise healthy patient diagnosed with an urological malignancy.