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Purpose
Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients.
Methods
170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan–Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints.
Results
High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18–14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35–32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92–3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22–6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70–2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02–4.67, p = 0.043). However, this did not prevail in multivariable analysis.
Conclusion
The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery.
Purpose
To test for regional differences in clear cell metastatic renal cell carcinoma (ccmRCC) patients across the USA.
Methods
The Surveillance, Epidemiology, and End Results (SEER) database (2000–2018) was used to tabulate patient (age at diagnosis, sex, race/ethnicity), tumor (N stage, sites of metastasis) and treatment characteristics (proportions of nephrectomy and systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models, tested the overall mortality (OM) adjusting for those patient, tumor and treatment characteristics.
Results
In 9882 ccmRCC patients, registry-specific patient counts ranged from 4025 (41%) to 189 (2%). Differences across registries existed for sex (24–36% female), race/ethnicity (1–75% non-Caucasian), N stage (N1 25–35%, NX 3–13%), proportions of nephrectomy (44–63%) and systemic therapy (41–56%). Significant inter-registry differences remained after adjustment for proportions of nephrectomy (46–63%) and systemic therapy (35–56%). Unadjusted 5-year OM ranged from 73 to 85%. In multivariable analyses, three registries exhibited significantly higher OM (SEER registry 5: hazard ratio (HR) 1.20, p = 0.0001; SEER registry 7:HR 1.15, p = 0.008M SEER registry 10: HR 1.15, p = 0.04), relative to the largest reference registry (n = 4025).
Conclusion
Important regional differences including patient, tumor and treatment characteristics exist, when ccmRCC patients included in the SEER database are studied. Even after adjustment for these characteristics, important OM differences persisted, which may require more detailed analyses to further investigate these unexpected differences.
Background
This study aimed to test the prognostic significance of pathologically confirmed lymph node invasion in metastatic renal cell carcinoma (mRCC) patients in this immunotherapy era.
Methods
Surgically treated mRCC patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Kaplan-Meier plots and multivariable Cox-regression models were fitted to test for differences in cancer-specific mortality (CSM) and overall mortality (OM) according to N stage (pN0 vs pN1 vs. pNx). Subgroup analyses addressing pN1 patients tested for CSM and OM differences according to postoperative systemic therapy status.
Results
Overall, 3149 surgically treated mRCC patients were identified. Of these patients, 443 (14%) were labeled as pN1, 812 (26%) as pN0, and 1894 (60%) as pNx. In Kaplan-Meier analyses, the median CSM-free survival was 15 months for pN1 versus 40 months for pN0 versus 35 months for pNx (P < 0.001). In multivariable Cox regression analyses, pN1 independently predicted higher CSM (hazard ratio [HR], 1.88; P < 0.01) and OM (HR, 1.95; P < 0.01) relative to pN0. In sensitivity analyses addressing pN1 patients, postoperative systemic therapy use independently predicted lower CSM (HR, 0.73; P < 0.01) and OM (HR, 0.71; P < 0.01).
Conclusion
Pathologically confirmed lymph node invasion independently predicted higher CSM and OM for surgically treated mRCC patients. For pN1 mRCC patients, use of postoperative systemic therapy was associated with lower CSM and OM. Consequently, N stage should be considered for individual patient counseling and clinical decision-making.
Background:
The treatment landscape of metastatic renal cell carcinoma (mRCC) has substantially advanced over the last three decades, whereby data from controlled clinical trials indicate significant improvements regarding patients’ overall survival (OS) in highly selected patient cohorts. The aim of this study is to evaluate the impact of potentially game changing drugs on patients’ outcomes by comparing three different historical mRCC treatment eras.
Methods:
In all, 914 mRCC patients who were diagnosed between July 1985 and September 2020 were included into this observational study and assigned to three different treatment eras [‘cytokine’, ‘first-generation tyrosine kinase inhibitors (TKIs)’, and ‘modern TKIs/immunotherapy’] based on the EMA approval dates of sunitinib (July 2006) and nivolumab (June 2015) in mRCC treatment. OS was considered the primary study endpoint. Kaplan–Meier analyses, log-rank tests, and uni- and multivariable Cox regression models were performed.
Results:
OS was significantly longer in patients of the modern TKIs/immunotherapy era (median OS not reached) as compared to the cytokine (2.4 years) and first-generation TKIs era (1.7 years, all p < 0.001). Moreover, patients of the modern TKIs/immunotherapy era demonstrated a significantly better prognosis [hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.32–0.55, p < 0.001] compared to those of the cytokine era, while no statistically significant difference was observed between the cytokine and the first-generation TKIs era cohort (HR: 1.12, 95% CI: 0.89–1.41, p = 0.341). Subgroup analyses stratified by the International Metastatic RCC Database Consortium (IMDC) risk groups showed a significantly longer OS in the modern TKIs/immunotherapy era as compared to first-generation TKIs and cytokines across all IMDC risk groups.
Conclusion:
Significant advances in the systemic medical treatment of mRCC during the recent decade and the introduction of immunotherapy exerted a major impact on patient outcomes in terms of OS in a real-life population.
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.
In this review, we revisit the pivotal role of fibroblast growth factor receptor 3 (FGFR3) in bladder cancer (BLCA), underscoring its prevalence in both non-muscle-invasive and muscle-invasive forms of the disease. FGFR3 mutations in up to half of BLCAs play a well-established role in tumorigenesis, shaping distinct tumor initiation patterns and impacting the tumor microenvironment (TME). Emphasizing the importance of considering epithelial-mesenchymal transition profile and TME status, we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3-mutated BLCAs. This writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3-mutated BLCA, stressing the pressing need to unravel resistance mechanisms and identify co-targets for future combinatorial studies. A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms, including secondary mutations, epigenetic alterations in pathway effectors, phenotypic heterogeneity, and population-specific variations within FGFR3 mutational status. Lastly, we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3-mutated BLCA.
Background
Patients with testicular germ cell tumors (TGCT) have a high cancer-specific survival rate. We aimed to determine the short- and long-term risk of arterial thromboembolic events (ATE), their impact on mortality, and risk factors for ATE in TGCT patients.
Methods
Patients with TGCT treated between 1994-2020 were included in a single-center retrospective cohort study. The primary outcome was ATE (i.e., acute coronary syndrome, ischemic stroke, acute peripheral arterial occlusion). Cumulative incidences were obtained in competing risk analysis. The impact of ATE on mortality was analyzed in a multi-state model. Cox-regression was used to explore short-and long term ATE-risk factors.
Results
Overall, 1,277 patients were included (median age: 35 years; seminoma: 56%, 44% cisplatin-based chemotherapy). Cumulative ATE-incidences at 1-, 10-, and 25-years were 0.6% (95% confidence interval [CI]: 0.3-1.1), 2.6% (1.8-3.7), and 12.0% (8.7-15.9). ATE diagnosis was independently associated with increased all-cause mortality (age-adjusted transition hazard ratio: 4.61 [95%CI: 2.40-8.85], p<0.001). Cisplatin-based chemotherapy was associated with ATE-risk within 1 year after TGCT diagnosis (1.4% vs 0%, p<0.001), whereas no differences were observed thereafter. Regarding long-term ATE-risk, a point-based risk score was derived (age ≥35, smoking, LDH ≥250IU/L), which efficiently stratified ATE risk (Harrel´s C: 0.71 [95% CI: 0.63–0.78]), with cumulative ATE-incidences in low-, intermediate- and high-risk patients of 3.9%, 11.4%, and 22.7%, respectively.
Conclusions
ATE represent a common complication in TGCT survivors and are associated with increased mortality. A simple point-based score efficiently stratifies long-term ATE-risk, whereas cisplatin-based chemotherapy increased short-term ATE risk.
