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Germ cell neoplasms of the testis are rare solid tumors predominantly in young men. Seminomas are slightly more frequent than nonseminomatous germ cell tumors. A special feature of seminomas is that they are sensitive to radiation, so that this represents an option in tumor stages with few metastases; however, the guideline recommendation is cautious due to the increased risk of secondary malignancies. In nonmetastasized tumor stages active surveillance is the primary approach to avoid overtreatment of patients. This is also the reason for primary nerve-sparing retroperitoneal lymph node dissection in cases of a low metastasis load. This concept has already been implemented in the American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN) guidelines, whereas in the European Association of Urology (EAU) guidelines it is still considered to be an individual approach., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: Gemäß den Richtlinien des Springer Medizin Verlags werden Autoren und Wissenschaftliche Leitung im Rahmen der Manuskripterstellung und Manuskriptfreigabe aufgefordert, eine vollständige Erklärung zu ihren finanziellen und nichtfinanziellen Interessen abzugeben. Autoren: D. Pfister: A. Finanzielle Interessen: Reise: Janssen, Bayer – Berater: MSD, AstraZeneca, Pfizer, Referent: Janssen. – B. Nichtfinanzielle Interessen: angestellter Urologe, Klinik für Urologie, Uro-Onkologie, spezielle urologische und Roboter-assistierte Chirurgie | Universitätsklinikum Köln (AÖR), Kerpener Str. 62, 50937 Köln | Mitgliedschaften: DGU, EAU, CAU. C. Rieger: A. Finanzielle Interessen: C. Rieger gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Assistenzarzt, Klinik für Urologie, Universitätsklinik Köln | Mitgliedschaften: DGRU, DGU. F. Seelemeyer: A. Finanzielle Interessen: F. Seelemeyer gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Assistenzarzt in der Klinik für Urologie, Uniklinik Köln | Mitgliedschaften: DGU, GESRU, EAU. A. Heidenreich: A. Finanzielle Interessen: A. Heidenreich gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Direktor der Klinik für Urologie, Uniklinik Köln | Mitgliedschaften: AUA, ASCO, DGU, DGHO, EAU, ESMO, SIO. Wissenschaftliche Leitung: Die vollständige Erklärung zum Interessenkonflikt der Wissenschaftlichen Leitung finden Sie am Kurs der zertifizierten Fortbildung auf www.springermedizin.de/cme . Der Verlag: erklärt, dass für die Publikation dieser CME-Fortbildung keine Sponsorengelder an den Verlag fließen. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

About 10% of patients with seminomatous testicuar germ cell tumors are diagnosed with clinical stage II/B. The current guideline recommended treatment options include systemic chemotherapy with 3 cycles PEB or radiation therapy with 30 Gy for CS IIA and 36 Gy for CS IIB. Despite a high cure rate of 90-94% and 82-90% for CS IIA and CS IIB, respectively, both options are associated with a high rate of treatment-associated long-term toxicities. A significantly increased risk for the development of secondary malignancies, cardiovascular and metabolic disease as well as an increased for treatment-associated mortality has been proven in various studies. Primary nerve sparing retroperitoneal lymph node dissection (nsRPLND) has been evaluated in 5 prospective and retrospective clinical studies and it has emerged as a valid treatment alternative. The relapse-rate after a median follow-up of 25-33 months is in the range of 11-30%, so that 70-90% of patients are cured without being subjected to chemotherapy and potential long-term toxicities. All relapsing patients have been cured with secondary salvage chemotherapy. The frequency of significant surgery-associated complications is low with 3-13%. Therapeutic success depends on the surgical experience of the various surgeons and the chosen template, so that this type of surgical interventions should only be performed in centres of excellence with dedicated surgeons. Preoperative evaluation of the new biomarker miR371 has been shown to predict the presence of metastatic disease with an accuracy of around 100% so that this marker might be used in daily routine prior to active treatment in CS IIA/B seminomas., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: The guideline-recommended treatment of choice for clinical stage IIA/B testicular germ cell tumors is chemotherapy with three cycles of PEB/four cycles of PE or, alternatively, radiation for seminomas. Despite their high curative efficacy, both options are associated with significant long-term toxicities. We evaluated the functional and oncological outcomes of primary retroperitoneal lymph node dissection (RPLND) as a therapeutic alternative., Patients and Methods: Between 2018 and 2022, 76 patients (n = 34 seminomas, n = 42 nonseminomas) underwent primary RPLND for marker-negative clinical stage IIA/B testicular germ cell cancer. All patients underwent nerve-sparing RPLND with a unilateral or bilateral template dissection and had a follow-up ≥ 3 months. None of the patients received adjuvant chemotherapy. In 24 patients, the serum concentration of miR371a-3p was evaluated preoperatively. Follow-up was performed according to EAU guidelines., Results: Median age and median follow-up were 30.1 (17-62) years and 29.3 (3-72) months, respectively. Mean operation time, blood loss, and duration of hospitalization were 131 (105-195) min, < 150 ml, and 4.5 (3-9) days, respectively. A Clavien-Dindo IIIa complication was experienced by 8 (10.9%) patients. Antegrade ejaculation was preserved in 90.8%. A mean number of 19 (7-68) lymph nodes were dissected. The mean number of positive lymph nodes was 1.1 (1-5), and the mean diameter of positive lymph nodes was 2.4 (0.8-4.6) cm. Eleven (14.5%) patients had stage pN0 (3/34 seminomas, 8/42 nonseminomas). In 24/27 patients (88.9%) miR371 was positive, and it was negative in 4/4 with pN0 and 3/3 (100%) with teratoma. An outfield relapse was experienced by 7 patients (9.2%), who then received salvage chemotherapy., Conclusion: Primary RPLND for marker-negative clinical stage IIA/B germ cell tumors results in high cure rates without adjuvant chemotherapy and is associated with a low rate of complications if performed in experienced hands. Therefore, primary RPLND should be included in the management of these patients., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Patients with marker-negative clinical stage IIA/B seminoma or nonseminoma represent a therapeutic challenge, as 20-30% might harbor nonmalignant histologies. MicroRNA 371a-3p (miR371) may represent a biomarker with diagnostic and predictive properties in testicular germ cell tumors (TGCTs). We evaluated the predictive accuracy of this biomarker in identifying the presence or absence of lymph node metastases (LNMs) in clinical stage IIA/B TGCT. In a cohort of 24 consecutive patients with marker-negative clinical stage IIA/B TGCT (n = 15 seminoma, n = 9 nonseminoma) serum miR371 was assessed 1 d before nerve-sparing retroperitoneal lymphadenectomy. Histology revealed metastatic TGCT in 22/24 patients (91.7%), with positive miR371a findings for 20 of these 22 patients with metastases (90.9%). Histology revealed no malignancy in one patient and lymphoma in another, both of whom had negative miR371a findings. One additional patient with pure teratoma and one with a microscopic seminomatous LNM had false-negative miR371a findings. The miR371 assay had sensitivity of 90.9% and specificity of 50%. The positive predictive value was 100.0% and the negative predictive value was 75.0%. According to the data available, miR371a represents a highly reliable, personalized tumor marker for predicting the presence of low-volume retroperitoneal LNMs in marker-negative TGCT. miR371 has potential for inclusion in the diagnostic armamentarium for men with equivocal lymph nodes to facilitate avoidance of unnecessary treatment and the associated toxicity. PATIENT SUMMARY: Our study demonstrates that blood tests for the biomarker miR371 are highly reliable in predicting the presence of lymph node metastases in patients with stage IIA/B testicular cancer. For patients with equivocal findings, use of this test may help in avoiding unnecessary treatment., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Radiation therapy and systemic chemotherapy are recommended treatment options in marker-negative clinical stage (CS) IIA/B seminoma. Despite high cure rates of 82-94%, both therapeutic options are associated with significant long-term toxicities., Objective: To evaluate the feasibility, oncological efficacy, and treatment-associated morbidity of primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) in CS IIA/B seminoma., Design, Setting, and Participants: A prospective, single-arm, clinical phase 2 trial including CS IIA/B seminoma patients was conducted., Intervention: Primary nerve-sparing retroperitoneal lymphadenectomy., Outcome Measurements and Statistical Analysis: Relapse-free and overall survival, surgery-associated complications according to the Clavien-Dindo classification, and Kaplan-Meier methods for survival calculation were assessed., Results and Limitations: Thirty patients at a mean age of 39.1 (34-52) yr with marker-negative CS IIA and IIB seminomas were recruited. The median follow-up was 22 (8-30) mo. Nineteen (63%) and 11 (36%) patients were diagnosed with stages IIA and B, respectively, at the time of primary diagnosis. Fourteen (47%) and 16 (53%) patients were diagnosed with CS IIA and IIB, respectively, at the time of nsRPLND. Twenty-seven and three patients underwent open and robot-assisted nsRPLND, respectively. The median operating room time was 125 (115-145) min, median blood loss was <150 ml, and median time of hospitalization was 4.5 (3-9) d. Four (13%) patients experienced Clavien-Dindo grade 3a complications. Lymph node histology revealed seminoma in 25 (80%) patients; two and three patients demonstrated embryonal carcinoma and benign disease, respectively. Sixteen patients underwent a serum analysis of miR371 preoperatively, which predicted metastatic disease in 12/13 and benign histology in 3/3 patients. Three of 30 (10%) patients developed an outfield relapse 4, 6, and 9 mo postoperatively and were salvaged by systemic chemotherapy. Limitations are the low patient number and length of follow-up., Conclusions: The nsRPLND approach results in a high cure rate at midterm follow-up and is associated with a low frequency of treatment-associated morbidities, making this approach a feasible alternative to radiation therapy or systemic chemotherapy., Patient Summary: The standard treatment of clinical stage IIA/B seminomas is radiation therapy or chemotherapy, which results in a significantly increased frequency of long-term toxicity and secondary neoplasms. In this trial, we demonstrate that nerve-sparing retroperitoneal lymph node dissection is a feasible therapeutic approach with low morbidity and high oncological efficacy., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Testis-sparing surgery (TSS) is a guideline-recommended treatment option for men with synchronous or metachronous bilateral testicular germ-cell tumor (GCT) or GCT in a solitary testicle. The tumor volume should not exceed 50% of the total testicular volume and serum concentrations of both testosterone and luteinizing hormone should be within the normal ranges. After tumor enucleation, patients should undergo adjuvant radiation of the testicle in case of germ cell neoplasia in situ. The local relapse rate is approximately 4% if TSS is performed properly. Physiological serum testosterone concentrations are achieved in more than 85% of patients, and approximately 50% of men with intact spermatogenesis can achieve paternity. The risk of systemic metastases is not increased by TSS. PATIENT SUMMARY: Testis-sparing surgery is the treatment of choice for men with testicular cancer in both testes or in men who have just one testis. In more than 85% of patients this approach results in maintenance of normal testosterone levels., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)