Role of Neoadjuvant Chemotherapy on Pathological, Functional, and Survival Outcomes of Upper Tract Urothelial Carcinoma Patients: A Systematic Review and Meta-Analysis.

The role of neoadjuvant chemotherapy (NAC) in upper tract urothelial cancer (UTUC) is not yet confirmed. Therefore, we conducted this review to pool the available evidence in this regard. We analyzed 14117 UTUC patients reported in 21 studies after searching 5 databases. The NAC was administered in 1983 patients and the remaining 12134 controls underwent radical nephroureterectomy (RNU) alone. Efficacy endpoints included pathological, functional, and survival outcomes. Safety was determined by overall and grade 3-4 complications. For dichotomous outcomes, the log odds ratio (logOR) was pooled, and for continuous variables, the crude mean difference was calculated along with its 95% CI. The NAC was associated with 10% complete pathological response (CPR), 42% pathological downstaging, 31% post-NAC advanced disease (pT3-4), 6% positive surgical margin, 18% lymph node metastasis (pN+), 24% lymphovascular invasion, and 29% mortality and recurrence at 5 years. Compared to controls, NAC resulted in increased risk of CPR [logOR=1.67; 95% CI, 0.11-3.23] and downstaging [logOR=1.30; 95% CI, 0.41-2.18] and reduced risk of advanced disease [logOR=-0.81; 95% CI, -1.51--0.11]. Renal function did not improve from baseline; however, it increased significantly after RNU. The NAC was associated with good survival/low mortality in the short term, with a sustained increase over time. Overall and grade 3-4 complications occurred in 25% and 7% of patients, respectively. Our findings support the potential benefits of NAC in enhancing pathological outcomes and possibly improving survival in UTUC patients undergoing RNU. The variability in response and associated complications underscore the importance of careful patient selection and tailored treatment approaches.

The Role of Lymph Node Dissection in the Management of Upper Urothelial Cancer: A Nodal Status-Based Meta-Analytical Study.

This systematic review was performed to study the prognostic value of lymph node dissection (LND) during nephroureterectomy in upper tract urothelial cancer (UTUC). Five databases were searched on September 11, 2022, to include studies that compared whether LND was performed, the extent of dissection (complete vs. incomplete), and the nodal status (positive "pN+" vs. negative "pN0"). Outcomes included prognosis (overall survival "OS," cancer-specific survival "CSS," disease-free survival "DFS," and recurrence-free survival "RFS") and complications. High-grade complications (≥ grade 3 according to the Clavien-Dindo classification). Data analysis were conducted through STATA. The pooled data are reported log odds ratio (logOR) with 95% CI. Thirty-three studies were analyzed. The LND resulted in improved 5-year OS [logOR=0.10; 95% CI: 0.06-0.15], 5-year CSS [logOR=0.10; 95% CI: 0.04- 0.17], and 10-year CSS [logOR=0.14; 95% CI: 0.06-0.21] when compared to non-LND. However, LND was associated with greater risk of high-grade complications [logOR=0.62; 95% CI: 0.26-0.98]. Complete LND was associated with lower risk of cancer-specific mortality than incomplete LND [logOR=-0.69; 95% CI: -1.22--0.16]. The pN0 patients had better 5-year OS; however, pN+ patients had better prognosis in DFS, RFS (at 2 and 5 years), and CSS (at 2, 5, and 10 years). Lymph node dissection provides a protective role in terms of 5-year OS and 5-year and 10-year CSS among UTUC patients. However, it is associated with higher risk of high-grade complications. The extent of dissection plays a minor prognostic role, while the positivity of resected nodes has great prognostic value in UTUC.

Clinical and genetic analysis of patients with cystinuria in the United Kingdom.

BACKGROUND AND OBJECTIVES: Cystinuria is a rare inherited renal stone disease. Mutations in the amino acid exchanger System b(0,+), the two subunits of which are encoded by SLC3A1 and SLC7A9, predominantly underlie this disease. The work analyzed the epidemiology of cystinuria and the influence of mutations in these two genes on disease severity in a United Kingdom cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prevalent patients were studied from 2012 to 2014 in the northeast and southwest of the United Kingdom. Clinical phenotypes were defined, and genetic analysis of SLC3A1 and SLC7A9 combining Sanger sequencing and multiplex ligation probe-dependent amplification was performed. RESULTS: In total, 76 patients (42 men and 34 women) were studied. All subjects had proven cystine stones. Median age of presentation (first stone episode) was 24 years old, but 21% of patients presented after 40 years old. Patients had varied clinical courses, with 37% of patients having ≥10 stone episodes; 70% had evidence of CKD, and 9% had reached ESRD as a result of cystinuria and its complications. Patients with cystinuria received a variety of different therapies, with no obvious treatment consensus. Notably, 20% of patients had staghorn calculi, with associated impaired renal function in 80% of these patients. Genetic analysis revealed that biallelic mutations were present in either SLC3A1 (n=27) or SLC7A9 (n=20); 22 patients had only one mutated allele detected (SLC3A1 in five patients and SLC7A9 in 17 patients). In total, 37 different mutant variant alleles were identified, including 12 novel mutations; 22% of mutations were caused by large gene rearrangements. No genotype-phenotype association was detected in this cohort. CONCLUSIONS: Patients with cystinuria in the United Kingdom often present atypically with staghorn calculi at ≥40 years old and commonly develop significant renal impairment. There is no association of clinical course with genotype. Treatments directed toward reducing stone burden need to be rationalized and developed to optimize patient care.

A review of tasquinimod in the treatment of advanced prostate cancer.

Castration resistant prostate cancer remains a major clinical burden and novel therapeutic options are urgently required to improve survival. Tasquinimod is an orally administered quinoline-3-carboxamide with potent antiangiogenic and antitumorigenic action that has shown promise in the treatment of advanced prostate cancers. This review explores both preclinical and clinical findings to date. In summary, tasquinimod has been shown to demonstrate a potent in vitro and in vivo anticancer action and completed early phase clinical trials have demonstrated good drug tolerance and prolonged progression-free survival. Although Phase III clinical trials are on-going, the findings to date highlight the promise of this drug in the treatment of advanced prostate cancer.