Retroperitoneal lymph node dissection in testicular germ cell tumours: indications, complications and special cases

Retroperitoneal lymph node dissection is an integral part of the stage-adapted therapy of germ cell tumours. Different approaches of retroperitoneal lymph node dissection are performed based on various indications. Nerve-sparing retroperitoneal lymph node dissection as a primary therapy option in non-seminomatous germ cell tumours in clinical stage I disease should be performed using a risk-adapted approach. Minor complications like infections of operative wounds, lymphoceles and paralytic ileus are described in about 14% of patients, major complications like chylous ascites and pulmonary artery embolism in 5,4% of patients. The most common long-term complication is retrograde ejaculation. Antegrade ejaculation rates of over 90% can be achieved with a nerve-sparing attempt. Post-chemotherapy retroperitoneal lymph node dissection is an integral part of the multimodality treatment of retroperitoneal residual masses after chemotherapy. For residual masses with a diameter of > 3 cm in advanced seminoma patients, FDG-PET is a reliable indicator for decision-making on retroperitoneal lymph node dissection. Residual retroperitoneal tumour masses appear in about 30% of patients with non-seminomatous germ cell tumours. These masses should be resected completely, irrespectively of their size, in patients with negative tumour markers or plateauing tumour markers. Post-chemotherapy lymph node dissection is a challenging procedure and should be performed at referral centres. In 25% of patients, resection of adjunctive organs is necessary in post-chemo lymph node dissection. Affection of abdominal aorta is described in 6 - 10% of all cases, affection of inferior vena cava in about 2% of cases. Post-chemo lymph node dissection is associated with a higher complication rate than nerve-sparing primary retroperitoneal lymph node dissection, including a significantly higher intraoperative blood loss and a significantly higher transfusion rate. With rates of 2 - 7%, chylous ascites occurs more often in post-chemo retroperitoneal lymph node dissection. Antegrade ejaculation can be preserved in up to 85% of patients. To preserve antegrade ejaculation and reduce morbidity, a nerve-sparing approach and template reduction in post-chemo retroperitoneal lymph node dissection is crucial and should be performed when possible

Late relapsing germ cell tumors with elevated tumor markers

Purpose!#!Late relapsing germ cell tumors (LR-GCT) are considered a rare distinct biologic entity as their clinical presentation and response to treatment is different to early recurrences. While serum tumor markers (AFP and ß-HCG) play an important role at the time of first diagnosis to correctly classify prognosis and treatment of germ cell tumors, they may not have the same significance in a late relapse situation.!##!Patients and methods!#!Thirty-seven patients with LR-GCT with elevated serum tumor markers were identified in our database. Twenty-six patients underwent primary surgical resection of the late relapsing tumor. Eleven patients received salvage chemotherapy and a post-chemotherapy residual tumor resection. Serum tumor markers, histological findings and oncological outcome were analyzed.!##!Results!#!In the histopathological specimen, viable cancer was found in 20 cases (54%) and teratoma was found in 16 cases (43%). In nine cases (24%), a somatic-type malignant transformation was present. In 19 of 37 patients (51.4%), the late relapse specimen presented a histological type of GCT, which was not present in the primary histology. Twenty-two patients (59.5%) were included in follow-up analysis. Mean and median follow-up time was 62.2 and 53 months, respectively. Seventeen patients (77.3%) suffered a relapse or had progressive disease after LR therapy. Five patients (22.7%) have been relapse-free after LR therapy (mean FU 61.6 months). Ten patients died of disease during follow-up (45.5%) and had a mean time from LR to death of 66.4 months. Eleven patients were alive at last follow-up (mean FU 62.2 months). Relapse and survival rate were similar between patients who received primary resection of LR tumor and patients who received salvage chemotherapy followed by surgery.!##!Conclusion!#!Patients with a late relapsing germ cell tumor and elevated markers have a poor prognosis and a high risk for another relapse independent on primary treatment. The histological type and aggressiveness of a late relapsing tumor cannot be predicted with serum tumor marker levels at the time of diagnosis of LR. In up to 54% of cases, primary histology did not coincide with LR histology. Therefore, we propose primary surgical resection of a late relapsing tumor if a complete resection is feasible in order to gain exact histology and tailor further treatment

Phase 2 Single-arm Trial of Primary Retroperitoneal Lymph Node Dissection in Patients with Seminomatous Testicular Germ Cell Tumors with Clinical Stage IIA/B (PRIMETEST)

BACKGROUND Primary retroperitoneal lymph node dissection (RPLND) for clinical stage (CS) IIA/B seminoma without adjuvant treatment is an experimental treatment to avoid radiotherapy- or chemotherapy-related toxicity from standard treatment. OBJECTIVE The PRIMETEST trial aimed to prospectively evaluate the oncological efficacy and surgical safety of primary RPLND. DESIGN, SETTING, AND PARTICIPANTS PRIMETEST is a single-arm, single-center prospective phase 2 trial. Patients with seminoma, unilateral retroperitoneal lymph node metastases <5 cm, and human chorionic gonadotropin levels <5 mU/ml were included. Patients with CS IIA/B seminoma at initial diagnosis, and recurrence under active surveillance or following adjuvant carboplatin for CS I disease were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Unilateral open or robot-assisted primary RPLND was performed. The primary endpoint of the study was progression-free survival (PFS) after 36 mo. The trial was considered positive if <30% of patients experienced a recurrence. RESULTS AND LIMITATIONS Between 2016 and 2021, 33 patients were accrued (nine with primary CS IIA/B, 19 recurrences during active surveillance, and five recurrences following adjuvant carboplatin). Thirteen and 20 patients had CS IIA and IIB, respectively. Open and robot-assisted RPLND procedures were performed in 14 (42%) and 19 (58%) patients, respectively. After a median follow-up of 32 mo (interquartile range 23-46), ten recurrences were detected (30%, 95% confidence interval: 16-49%); thus, the primary endpoint was not met. Infield recurrences occurred in three of ten patients. The current analysis of risk factors could not identify the predictors of recurrence. Three of 33 patients (9%) presented with pN0. CONCLUSIONS The PRIMETEST trial did not meet its primary endpoint. Nevertheless, PFS of 70% after a median follow-up of 32 mo suggests this approach to be of interest for highly selected patients. Selection criteria, however, need to be defined and validated in a larger prospective cohort of patients. Until then, surgery alone for the treatment of patients with CS IIA/B seminoma cannot be recommended outside of a clinical trial setting. PATIENT SUMMARY In this study, we investigated primary surgery as an alternative to conventional treatment (chemotherapy or radiation therapy) in patients with metastatic seminoma. The primary objective of the study, to prevent at least 30% of patients from recurrence, was not met. However, certain patients may benefit from this approach and thereby avoid chemotherapy or radiation therapy. Predictive factors need to be analyzed to better select patients for this surgery-only approach

Short-term and long-term outcomes after resection of thoracic growing teratoma syndrome

PURPOSE Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not available. METHODS We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan-Meier method. RESULTS Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19-50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (n = 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13-237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively. CONCLUSIONS TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections

Current developments and treatment options in the management of growing teratoma syndrome

Background The diagnosis of growing teratoma syndrome (GTS) is complex and due to the small number of cases it is difficult to evaluate the treatment options. A better understanding of the development of GTS and sensitization to its paradoxical clinical presentation is crucial for a successful treatment strategy. Objectives The aim of this review is to summarize the current literature on the development of and treatment options for GTS. Based on this, a molecular model for the development of GTS is proposed and an evidence-based treatment strategy is recommended. Materials and methods A selective literature search was carried out via PubMed. Results GTS is characterized by proliferating metastatic postpubertal teratoma without further nonseminomatous components, despite decreasing or normalizing concentrations of the serum tumor markers human chorionic gonadotropin beta (beta-HCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) during chemotherapy. Conclusion We postulate that during chemotherapy, embryonal carcinoma cells develop into a population of transiently amplifying cells that resemble the stem cell pool of a germ cell layer tissue. This population has the potential to self-renew or to differentiate into all three germ cell layers (mesoderm/endoderm/ectoderm), thereby promoting growth of a teratoma. Complete resection of the entire teratoma is therefore necessary. Due to the high incidence of concurrent resection of organs, teratoma resections should be performed in multidisciplinary and specialized centers

Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection- A 13-year follow-up analysis of a phase III trial cohort

Background: One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up. Methods: Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND thorn two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75). Results: With a median follow-up of 13.8 years (0-22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96-100%)/92% (CI 89-99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87-97%)/ 93% (CI 86-97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01). Conclusions: With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities. 2021 Elsevier Ltd. All rights reserved