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Simple Summary: Wilms tumor (WT), as the most common renal tumor in childhood, is treated very successfully within prospective trials and studies. The association with various genetic alterations has been studied, but it is still unclear why a WT develops in a specific child and why some children suffer from relapse. Genetic risk and external, environmental factors need further attention. Parental age at birth plays a role in various childhood diseases, so it is reasonable to also investigate whether older parental age is a risk factor for the development of childhood renal tumors. We could demonstrate that parental age has no correlation with the incidence of renal tumors in childhood. Despite excellent outcomes, many open questions remain about Wilms tumor (WT). Influences and risk factors for tumorigenesis, as well as tumor aggressiveness and recurrence, are not fully understood. Parental age plays a role in various childhood diseases and is also discussed as a risk factor for childhood cancer. We analyzed both maternal and paternal age at birth as risk factors for the occurrence of Wilms and non-Wilms tumors in children and investigated whether older maternal or paternal age is associated with a higher tumor incidence. During 1990 and 2019 we collected data from 3991 patients from the multicenter studies SIOP9/GPO, SIOP 93-01/GPOH, and SIOP 2001/GPOH, of whom maternal and paternal age was available in 2277 cases. Data from the Federal Statistical Office containing live births in Germany from 1990–2019 served as a comparative database. For maternal age at birth, the control data yielded 22,451,412 cases and for paternal age yielded 19,046,314 cases. Comparing maternal and paternal ages of the study patients with those of the control data, we confirmed that higher parental age is not correlated with the incidence of renal tumors in childhood. Mean ages of fathers and mothers in patients and the control cohort increased between 1991 and 2019 (fathers: 30.28 vs. 34.04; mothers: 27.68 vs. 29.79 in the patient group and 31.29 vs. 34.23 and 28.88 vs. 32.67 in the control group, respectively) without higher numbers of patients with kidney cancer over time. No influence was found for the subtype of cancer nor for syndromes. In addition, overall survival of patients is independent of the year of diagnosis and the age of the parents but depends on histology type and stage in WT. [ABSTRACT FROM AUTHOR]

Simple Summary: In SIOP, trials and studies for Wilms tumor (WT) start with chemotherapy before the surgical removal of the tumor. The aim of this study is to find out whether the time between the start of preoperative chemotherapy and surgery has an influence on the outcome of WT patients. Therefore, we analyzed a completely German, Austrian, and Swiss cohort of 2561 unilateral WT patients pretreated between 1989 and 2022. This retrospective analysis shows no such influence on the occurrence of relapses and survival in unilateral WTs. However, in bilateral tumors with prolonged pretreatment, to achieve as many nephron-sparing surgeries as possible, preoperative treatment should not exceed 120 days due to an increased risk of relapses. (1) Background: Wilms tumor (WT) treated preoperatively is cured in over 90% of cases. However, how long preoperative chemotherapy can be given is unknown. (2) Methods: 2561/3030 patients with WT (age < 18 years) treated between 1989 and 2022 according to SIOP-9/GPOH, SIOP-93-01/GPOH, and SIOP-2001/GPOH are retrospectively analyzed to assess the risk of time to surgery (TTS) for relapse-free survival (RFS) and overall survival (OS). (3) Results: TTS was calculated for all surgeries, with the mean being 39 days (38.5 ± 12.5) for unilateral tumors (UWT) and 70 days (69.9 ± 32.7) for bilateral disease (BWT). Relapse occurred in 347 patients, of which 63 (2.5%) were local, 199 (7.8%) were metastatic, and 85 (3.3%) were combined. Moreover, 184 patients (7.2%) died, 152 (5.9%) due to tumor progression. In UWT, recurrences and mortality are independent of TTS. For BWT without metastases at diagnosis, the incidence of recurrence is less than 18% up to 120 days and increases to 29% after 120 days, and to 60% after 150 days. The risk of relapse (Hazard Ratio) adjusted for age, local stage, and histological risk group increases to 2.87 after 120 days (CI 1.19–7.95, p = 0.022) and to 4.62 after 150 days (CI 1.17–18.26, p = 0.029). In metastatic BWT, no influence of TTS is detected. (4) Conclusions: The length of preoperative chemotherapy has no negative impact on RFS or OS in UWT. In BWT without metastatic disease, surgery should be performed before day 120, as the risk of recurrence increases significantly thereafter. [ABSTRACT FROM AUTHOR]

Simple Summary: Wilms tumor (WT) is the most common solid renal tumor in childhood. Today, more than 90% are alive 5 years after treatment. If the tumor extends into the major abdominal vessels, treatment still faces significant challenges. In these cases, tumor removal from the vessel is also required, sometimes requiring complex management. Knowledge of factors that positively or negatively affect treatment and survival is therefore of particular interest. We, therefore, compiled data on this small group of WT patients and evaluated them in terms of survival. This revealed that certain tumor-related features, as well as the presence or absence of metastases, significantly affect survival. This information helps us to further improve the treatment for this group of patients. (1) Background: Vena cava thrombus (VCT) is rare in Wilms tumor (WT) (4–10%). The aim of this study is to identify factors for an outcome to improve treatment for better survival. (2) Methods: 148/3015 patients with WT (aged < 18 years) and VCT, prospectively enrolled over a period of 32 years (1989–2020) by the German Society for Pediatric Oncology and Hematology (SIOP-9/GPOH, SIOP-93-01/GPOH and SIOP-2001/GPOH), are retrospectively analyzed to describe clinical features, response to preoperative chemotherapy (PC) (142 patients) and surgical interventions and to evaluate risk factors for overall survival (OS). (3) Results: 14 VCT regressed completely with PC and another 12 in parts. The thrombus was completely removed in 111 (85.4%), incompletely in 16 (12.3%), and not removed in 3 (2.3%). The type of removal is unknown in four patients. Patients without VCT have a significantly (p < 0.001) better OS (97.8%) than those with VCT (90.1%). OS after complete resection is (89.9%), after incomplete (93.8%) and with no resection (100%). Patients with anaplasia or stage IV without complete remission (CR) after PC had a significantly worse OS compared to the remaining patients with VCT (77.1% vs. 94.4%; p = 0.002). (4) Conclusions: As a result of our study, two risk factors for poor outcomes in WT patients with VCT emerge: diffuse anaplasia and metastatic disease, especially those with non-CR after PC. [ABSTRACT FROM AUTHOR]

Simple Summary: It is well known that different cancer predisposition syndromes are associated with characteristic WT-features. The following findings from our retrospective analysis of patients with nephroblastoma treated according to the SIOP/GPOH trials between 1989 and 2017 are relevant: (1) The outcome of patients with a cancer predisposition syndrome is not always favorable despite early diagnosis, small tumors and less metastatic disease. This finding is partly depending on complications related to the underlying syndrome. (2) Predisposition syndromes seem to be underdiagnosed as several clinical and pathological features of Wilms tumor being clearly linked to a cancer predisposition syndrome did not lead to genetic counseling before and after WT diagnosis. As a conclusion, in children with a nephroblastoma and specific clinical and pathological features that are in line with a nephroblastoma cancer predisposition syndrome such a syndrome should always be considered and ruled out if unknown at the time of tumor diagnosis. (1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. (3) Results: Genitourinary malformations (GU, N = 66, 2.3%), Beckwith-Wiedemann spectrum (BWS, N = 32, 1.1%), isolated hemihypertrophy (IHH, N = 29, 1.0%), Denys-Drash syndrome (DDS, N = 24, 0.8%) and WAGR syndrome (N = 20, 0.7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2% vs. 18%), but more often nephroblastomatosis (12.9% vs. 1.9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4% increase) and favorable in BWS (86.9% reduction). The event-free survival (EFS) of patients with BWS was significantly (p = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable. [ABSTRACT FROM AUTHOR]