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Testicular germ cell tumours (TGCTs) are the most frequent cancer type in young men and originate from the common precursor germ cell neoplasia in situ (GCNIS). For decades, clinical management of patients with TGCT has relied on classic serum tumour markers: α-fetoprotein, human chorionic gonadotropin subunit-β and lactate dehydrogenase. In the past 10 years, microRNAs have been shown to outperform classic serum tumour markers in the diagnosis of primary tumours and in follow-up monitoring and prediction of relapse. miR-371a-3p is the most consistent marker and exhibits >90% diagnostic sensitivity and specificity in TGCT. However, miR-371a-3p cannot be used to diagnose GCNIS or mature teratoma. Future efforts must technically standardize the microRNA-based methods internationally and introduce miR-371a-3p as a molecular liquid biopsy-based marker for TGCTs in the clinic.Here, the authors discuss embryonic microRNAs that are highly expressed in testicular germ cell tumours, critically assess the clinical utility of monitoring these microRNAs in the circulation and compare their diagnostic performance with the classic serum tumour markers.

Background/Objectives: Retroperitoneal lymph node dissection (RPLND) plays a crucial role in the staging and treatment of testicular cancer and is often mandatory. RPLND is associated with a high risk of morbidity. The use of minimally invasive techniques has significantly increased the number of robotic procedures performed over the last few years. This study aimed to analyze the perioperative and postoperative outcomes and trends of an increasing number of surgeries performed. Materials and Methods: We retrospectively analyzed 30 robotic RPLNDs (R-RPLNDs) performed at our testicular cancer center between 2020 and 2024. Logistic regression analyses were used to analyze the independent variables of operative time (OT), hospital stay (HS), estimated blood loss, lymph node yield, and complications according to the Clavien–Dindo classification system. The independent predictors included case number, clinical stage, post-chemotherapy status, preoperative retroperitoneal tumor mass, and body mass index. Furthermore, the patients were categorized into three groups: group A (cases 1–10), group B (cases 11–20), and group C (cases 21–30). A Kruskal–Wallis test was performed to assess differences among the groups concerning OT, HS, and lymph node yield. Results: OT significantly decreased with an increasing number of cases (p < 0.001), and HS was significantly affected by overall complications (p = 0.0006). There were two major perioperative complications (6.6%). No factors predicted overall complications or Clavien–Dindo grades I-II or III–V. The Kruskal–Wallis test showed a significant difference (p < 0.05) in OT and HS for group C. Conclusions: R-RPLND for GCTs demonstrates a clear learning curve, with significant improvements in OT, HS, and complication rates as surgeons gain experience. Overall, the low complication rates for R-RPLND did not indicate predictive factors for perioperative or postoperative complications. RPLND presents promising potential as a safe and effective treatment for GCTs, especially when performed by experienced surgeons in specialized centers.

Introduction: Testicular germ cell tumors (TGCTs) are a paradigm for the use of serum tumor markers in clinical management. However, conventional markers such as alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) have quite limited sensitivities and specificities. Within the last decade, the microRNA-371a-3p (miR371) emerged as a possible new biomarker with promising features. Areas covered: This review covers the typical features as well as possible clinical applications of miR371 in TGCT patients, such as initial diagnosis, therapy monitoring, and follow-up. Additionally, technical issues are discussed. Expert opinion: With a sensitivity of around 90% and specificity >90%, miR371 clearly outperforms the classical serum tumor markers in TGCTs. The unique features of the test involve the potential of modifying recent standards of care in TGCT. In particular, miR371 is expected to aid clinical decision-making in scenarios such as discriminating small testicular TGCT masses from benign ones prior to surgery, assessing equivocal lymphadenopathies, and monitoring chemotherapy results. Likewise, it is expected to make follow-up easier by reducing the intensity of examinations and by sparing imaging procedures. Overall, the data presently available are promising, but further prospective studies are required before the test can be implemented in standard clinical care.

Background/Purpose: Retroperitoneal lymph node dissection (RPLND) plays a crucial role in the surgical management of testicular cancer. However, RPLND is associated with a high risk of morbidity. Currently, open RPLND (O-RPLND) is considered the gold standard for surgical treatment. The use of minimally invasive techniques has increased significantly over the last few years. This study aimed to compare the safety and oncological outcomes of open (O-RPLND) and robotic (R-RPLND) retroperitoneal lymph node dissection for testicular cancer. Materials and Methods: We retrospectively analyzed all the patients who underwent RPLND at our testicular cancer center. Standard O-RPLND was performed with the usual equipment, and R-RPLND was performed with the Da Vinci X/Xi surgical system. The pre- and perioperative parameters and the postoperative complications (Clavien–Dindo classification), anejaculation, and the relapse rate were recorded. The association between the clinicopathological variables and the complications and relapse was assessed using regression analyses. Results: Sixty-five patients underwent RPLND during 2017–2024 due to testicular cancer (TC), with thirty-one (47.7%) receiving R-RPLND, including seventeen patients post-chemotherapy (55%). Meanwhile, 34 (52.3%) underwent O-RPLND, comprising 31 patients post-chemotherapy (91%). R-RPLND demonstrated excellent results compared to O-RPLND in terms of the operative time (OT) (p < 0.00001). The R-RPLND group had two (6.5%) high-grade (Clavien–Dindo III–V) complications, while four (11.8%) high-grade complications were noted in the O-RPLND group. R-RPLND was linked to a shorter OT (p < 0.00001). The hospital stay for R-RPLND was, on average, 2.7 days shorter. In logistic regression analysis, R-RPLND was non-inferior to O-RPLND for overall complications (p = 0.6) and low-grade Clavien–Dindo (I-II) (p = 0.2) and high-grade Clavien–Dindo (≥III) complications (p = 0.7). The median follow-up was 13 months for R-RPLND and 38 months for O-RPLND. Two relapses were observed in the R-RPLND group (6.5%), and two in the O-RPLND group (5.9%). One patient who underwent R-RPLND developed field-edge recurrence. No significant differences in the relapse and anejaculation rates were found between R-RPLND and O-RPLND (p = 0.9 and p = 0.8, respectively). Conclusions: In conclusion, R-RPLND is a feasible procedure with a low complication rate and an acceptable oncological outcome. It has proven to be significantly shorter to O-RPLND in relation to the lengths of HS and OT. However, R-RPLND is a demanding procedure with a considerable learning curve.

The pathogenesis of testicular germ cell tumours (GCTs) is still incompletely understood. Any progress in its understanding must derive from observational studies. Recently, it has been suggested that the incidence of GCTs may follow a seasonal pattern based on circannual changes in the Vitamin D serum levels, with maximum incidence rates in winter months. To examine this promising hypothesis, we studied monthly incidence rates of testicular GCTs in Germany by analysing 30,988 GCT cases aged 15–69 years, diagnosed during 2009–2019. Monthly incident case numbers with data regarding histology and patient age were obtained from the Robert Koch Institut, Berlin, along with annual male population counts. We used precision weighting for deriving pooled monthly incidence rates for GCTs of the period 2009–2019. We stratified pooled rates by histology (seminoma and nonseminoma) and age (15–39 and 40–69 years). By assuming a cyclical effect, we used an estimator of the intensity of seasonal occurrence and report seasonal relative risks (RR). The mean monthly incidence rate was 11.93/10 5 person-months. The seasonal RR for testicular cancer over-all is 1.022 (95% CI 1.000–1.054). The highest seasonal RR was found in the subgroup of nonseminoma aged 15–39 years, with a RR 1.044 (95% CI 1.000–1.112). The comparison of the pooled monthly rates of the winter months (October—March) with the summer months (April-September) revealed a maximum relative difference of 5% (95% CI 1–10%) for nonseminoma, aged 15–39 years. We conclude that there is no evidence of a seasonal variation of incidence rates of testicular cancer. Our results are at odds with an Austrian study, but the present data appear sound because the results were obtained with precision weighted monthly incidence rates in a large population of GCT cases.

PurposeOne of the main issues in testicular germ cell tumors (TGCTs) management is to reduce the necessary amount of treatment to achieve cure. Excess treatment burden may arise from late diagnosis of the primary as well as from false positive or negative staging results. Correct imaging is of paramount importance for successful management of TGCT. The aim of this review is to point out the current state of the art as well as innovative developments in TGCT imaging on the basis of three common challenging clinical situations.MethodsA selective literature search was performed in PubMed, Medline as well as in recent conference proceedings.ResultsRegarding small testicular lesions, recent studies using elastography, contrast-enhanced ultrasound or magnetic resonance imaging (MRI) showed promising data for differentiation between benign and malignant histology. For borderline enlarged lymph nodes FDG-PET-CT performance is unsatisfactory, promising new techniques as lymphotropic nanoparticle-enhanced MRI is the subject of research in this field. Regarding the assessment of postchemotherapeutic residual masses, the use of conventional computerized tomography (CT) together with serum tumor markers is still the standard of care. To avoid overtreatment in this setting, new imaging modalities like diffusion-weighted MRI and radiomics are currently under investigation. For follow-up of clinical stage I TGCTs, the use of MRI is non-inferior to CT while omitting radiation exposure.ConclusionFurther efforts should be made to refine imaging for TGCT patients, which is of high relevance for the guidance of treatment decisions as well as the associated treatment burdens and oncological outcomes.

PurposeLeydig-cell tumours (LCT) of the testis are poorly understood clinically. The aim of this report is to analyse the clinical characteristics of LCT in a large patient sample and to compare these findings with corresponding data of germ-cell tumours (GCT).MethodsIn a sample of 208 patients treated during 1995–2017 in 33 institutions, the following characteristics were registered: age, presenting symptoms, primary tumour size, testis-sparing surgery (TSS) or orchiectomy, malignancy, laterality, medical history, and outcome. Data analysis included descriptive statistical methods and logistic regression analysis.ResultsThe ratio LCT:GCT is 1:23 (4.4%). The findings are as follows: median age 41 years, undescended testis 8%, bilateral LCTs 3%, malignant LCT 2.5%, contralateral GCT 2.5%, incidental detection 28%, scrotal symptoms 43%, infertility 18%, elevated estradiol levels 29%. TSS was performed in 56% with no local relapse. Of the patients with malignant LCT, one was cured through surgery.ConclusionLCT is rare, with a relative frequency (relative to GCT) of 1:23. Malignancy is found in 2.5%. LCT and GCT share a number of clinical features, e.g. bilaterality, history of undescended testis, and presenting age. TSS is safe in benign LCT. Surgery is the treatment of choice in malignant LCT.

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: ‘neutral’ (n = 228) with normal sex hormone homeostasis, ‘testicle’ (n = 91) with elevated T and E2, low pituitary hormones, and finally ‘pituitary’ subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Purpose microRNA-371a-3p (M371) is considered a highly sensitive and specific serum biomarker of testicular germ cell tumours (GCTs). However, little is known about the expression of M371 in nontesticular malignancies (NTMs), so far. As knowledge about the expression of the marker in other malignancies is a prerequisite for the clinical application of the test we aimed to explore the M371 expression in other cancers. Methods M371 serum levels were measured in 137 patients with NTM of 12 different neoplastic entities using the IVDR-certified M371-Test for quantitative real-time PCR. Median M371 serum levels and percentages of M371 level elevations were calculated for the entire NTM group and for entity-specific subgroups. The results were compared with GCT patients ( n  = 20) and with tumour-free male controls ( n  = 20) using descriptive statistical methods. Results Eight patients with NTMs had M371 serum level elevations, corresponding to a false-positive rate (FPR) of 5.84% (95% confidence intervals (CIs) 2.55–11.18%). Expression rates in GCTs and controls were 100% and zero, respectively. Thus, the specificity of the M371-Test for GCT is 94.90% (95% CI 90.21–97.77%) when all NTMs and tumour-free controls are considered. Remarkably, three out of 5 patients with multiple myeloma had elevated M371 levels. Conclusion The false-positive rate of the M371-Test in other malignancies than GCT is very low, and almost identical with that in healthy males, corresponding to a high specificity of 94.9% for detection of GCT. The surprising finding of M371 elevations in patients with multiple myeloma needs further investigation.

Objectives This work aimed to document four new cases with giant testicular germ cell tumour (GCT) and to evaluate their relative incidence and clinical characteristics based on a literature survey. Despite the well‐established trend over time towards declining tumour sizes in testicular GCTs, giant testicular tumours (>15 cm in diameter) are still reported in present times. Patients, Methods GCT patients treated during 2010–2025 were retrospectively evaluated with tabulating the following data: size of primary tumour (mm), age (years), histology, side and clinical stage (CS). The following parameters were calculated: relative frequency of giant GCTs; median tumour size in all GCTs and in various subgroups. A literature survey was conducted to identify previously published giant testicular GCTs followed by a descriptive evaluation of those cases. Results Four (0.5%) giant GCTs were identified among 860 GCT patients, two seminomas and two nonseminomas, all having CS3 disease, two of whom were cured. The median tumour size was 32 mm in all GCTs, and 30 mm and 35 mm in seminomas (n = 541) and nonseminomas (n = 319), respectively. Median tumour size was significantly smaller in CS1 cases than in those with CS > 1 (32 mm vs. 38 mm). Of the 40 cases identified with the literature survey, 24 were nonseminomas, 62% were left‐sided, median age was 36 years, and 80% were cured. Diagnostic delay is the most frequent cause of excessive tumour growth. Conclusions Giant testicular tumours are observed in 0.5% of all GCT patients while the median tumour size of 32 mm observed herein is consistent with current reports. In most cases of giant GCT, personal misapprehension of the swelling, lack of knowledge or shame appears to be the key element causing diagnostic delay and consequently, extraordinary tumour growth. Information campaigns including individuals from socioeconomically underprivileged groups could help to increase men's awareness of genital diseases.