Open Access

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.

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.

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.