Nonseminomatous Testicular Germ Cell Tumors Research Articles

Cut-offs for relapse detection in men with stage I testicular germ cell tumors during active surveillance within a prospective multicentre cohort study using either raw or housekeeper normalized miR-371a-3p serum levels

PurposeMiR-371a-3p represents a novel liquid biomarker that detects all histologies of germ-cell tumors (GCT) except teratoma. However, it is currently unclear whether miR-371a-3p results obtained directly from RT-PCR (raw Cq) or normalized for housekeeper genes and transformed into the relative quantity (RQ) value should be used and at what cut-off level. The purpose of this research was to evaluate, which values should be used, and a potential cut-off level for relapse-detection to inform subsequent studies. Materials and MethodsWe applied a CE-certified qRT-PCR test to measure miR-371a-3p at each follow-up visit during active surveillance in 34 men with stage I testicular GCT. MiR-371a-3p levels were calculated by the ΔΔ method. ResultsAbout 18 Patients had pure seminoma and 16 had mixed or nonseminomatous testicular GCT. Recurrences were detected in 10 patients and were correctly identified by both raw and housekeeper-normalized miR-371a-3p serum levels. The raw Cq, with a cut-off value of <28, resulted in only 1 false positive (3%), whereas RQ, with a cut-off value of >15, produced 6 false positive results (17%). Most of these false positive results normalized in subsequent measurements. The RQ approach detected recurrence in 1 patient 6 months earlier than the raw Cq approach. ConclusionOur preliminary data suggest that this CE-certified assay, using previously suggested cut-off values, is a promising method for detecting disease recurrence, provided a confirmatory second test is conducted to identify false positive results. To avoid unnecessary scans or overtreatment, we are currently validating this assay and cut-offs in a prospective cohort study.

The clinical value of complete blood count-based immun parameter in predicting testicular cancer pathology and prognosis

Aim: The management of testicular cancer (TC) requires more specific and applicable biomarkers. We aimed to determine the ability of complete blood count (CBC) based inflammatory markers to predict tumor pathology and prognosis in TC. Methods: Patients who underwent inguinal orchiectomy for testicular germ cell tumors (TGCTs) at our hospital between January 2011 and December 2022 were included in the study. The medical records of patients with pathologically confirmed TC, including demographics, preoperative tumor markers, preoperative CBC, tumor characteristics, pathological outcomes, postoperative follow-up, and survival outcomes, were retrospectively collected. CBC-based inflammatory markers were compared between seminomatous and non-seminomatous TGCTs. To determine the independent prognostic significance of survival, the data were analyzed and fitted to the multivariate Cox proportional risk regression model. Results: The median follow-up was 48 (1-140) months. In our chord, 69 patients had seminomatous TGCTs (Group 1), and 66 had non-seminomatous TGCTs (Group 2). The median ages of Groups 1 and 2 were 35 (22-74) years and 31 (21-72) years(p

Paraneoplastic Hyperthyroidism in Advanced Testicular Non-Seminomatous Germ Cell Tumors: Prevalence and Clinical Management

Introduction: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes. Methods: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods. Results: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients. Conclusion: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium

AimsTo resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). Patients and methodsUsing the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. ResultsAmong 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). ConclusionTeratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

Abstract 6450: High mobility group protein 2 (HMGA2) is highly expressed in a broad range of human cancers

Abstract The high mobility group protein 2 (HMGA2) is an essential component of the enhanceosome. It can attach to AT-rich binding sites in the DNA minor groove, affect the conformation of the DNA, and thereby modify the transcription of numerous genes. HMGA2 is preferentially expressed during organogenesis. Aberrant expression of HMGA2 in adult tissues is commonly associated with tumor formation and cancer aggressiveness. Accordingly, HMGA2 represents a potential drug target. To better comprehend the role of HMGA2 expression in cancer, a tissue microarray containing 8,344 samples from 115 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. In normal tissues, a strong nuclear HMGA2 staining was limited to few cell types from the amnion, placenta, seminal vesicle, endocervix, fallopian tube, and respiratory epithelium. HMGA2 expression was generally markedly higher in cancer than in corresponding normal tissues. HMGA2 staining was found in 2,695 (42.7%) of the 6,313 interpretable tumor samples, including 701 (11.1%) with weak, 769 (12.2%) with moderate, and 1,225 (19.4%) with strong positivity. A total of 93 of 115 tumor categories showed HMGA2 expression in at least one case, and 69 tumor categories included at least one case with strong HMGA2 staining. The frequency of HMGA2 positivity was particularly high in cancers of the ovary and the endometrium (52.6-92.6%), pancreatico-biliary cancers (48.1-75.5%), thyroidal neoplasms (53.4-95%), salivary gland neoplasms (66.7-98%), nonseminomatous testicular germ cell tumors (73.5-93.5%), colorectal adenocarcinoma (81.6%), papillary renal cell carcinoma (68.2%), and in squamous cell carcinomas (36-81.5%). Tumor entities with a particularly low expression of HMGA2 included prostatic adenocarcinomas (1.3-4%), non-invasive urothelial carcinomas (1.8-4.3%), hepatocellular carcinoma (3.2%), and non-Hodgkin’s lymphomas (0%) It is concluded, that HMGA2 is highly expressed in a very broad range of tumor entities. These findings emphasize a potential role of HMGA2 as a drug target and demonstrate utility for HMGA2 IHC for the distinction of neoplastic from non-neoplastic tissues in several organs. Citation Format: Katharina Möller, Florian Lutz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Till Krech, Stefan Steurer, Christoph Fraune, Sarah Minner, Natalia Gorbokon, Maximilian Lennartz, Eike Burandt, Anne Menz. High mobility group protein 2 (HMGA2) is highly expressed in a broad range of human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6450.

Utility of circulating tumor DNA (ctDNA) as a predictive biomarker for disease monitoring in patients with non-seminomatous germ-cell tumor (NSGCT).

500 Background: Serum tumor markers (STM) are currently utilized in the management of testicular NSGCT. However, STMs are normal in a substantial proportion of patients with NSGCT (up to 40%) and can be falsely elevated in certain other clinical conditions. Therefore, a highly sensitive and specific biomarker for NSGCT can be helpful for disease monitoring with diagnostic and therapeutic implications. Herein, we test the clinical utility of ctDNA to predict patient outcomes and monitor treatment response in stage II-III NSGCT. Methods: A total of 106 plasma samples were collected from a cohort of 25 Stage II-III NSGCT patients post-orchiectomy with a median age of 29 years (IQR: 26.8-38.8) and a median follow-up of 10 months (IQR: 7.2-17.5). Longitudinal ctDNA testing was performed using a personalized, tumor-informed ctDNA assay (Signatera bespoke mPCR-NGS assay). ctDNA results were analyzed and evaluated for their correlation with clinical outcomes (event-free survival [EFS]) during surveillance after first-line therapy (retroperitoneal lymph node dissection [RPLND] or chemotherapy) or after salvage chemotherapy. EFS is described as the interval from orchiectomy to the date of recurrence or evidence of residual/persistent disease after the completion of RPLND or chemotherapy. Results: Of 25 patients, 28% (7/25) had stage II and 72% (18/25) had stage III disease. Five patients with stage II disease underwent RPLND, and all tested positive for ctDNA prior to RPLND. Of the 18 patients with stage III disease, 83.3% (15/18) tested ctDNA positive pre-chemotherapy. For patients who completed 1st line treatment with RPLND or chemotherapy and had ctDNA testing post-completion of therapy, none of the patients who tested negative for ctDNA experienced relapse (recurrence rate: 0%, 0/6) compared to a recurrence rate of 30.8% (4/13) in patients who had normal STM levels. The detection of ctDNA was associated with a significantly shorter EFS (HR=11.4, 95%Cl 1.09-1537, p=0.041) while elevated STM results were not (HR=2.14, 95%Cl 0.51-8.94, p=0.298). ctDNA-positivity remained strongly associated with poor EFS (HR=12.98, 95%CI 1.17-1869, p=0.035) when adjusted for STM status. For patients who progressed after 1st line therapy and were treated with salvage chemotherapy, no events were seen in those who were ctDNA negative after therapy (0/6) compared with an event rate of 25% (2/8) in patients with normal STMs. Conclusions: Personalized monitoring of ctDNA seems predictive for recurrence in patients with NSGCT. To the best of our knowledge, this is one of the first reports presenting the clinical implications of ctDNA monitoring in this patient population. Our findings suggest that ctDNA monitoring may help optimize clinical decision-making, however, larger prospective studies are needed to validate the findings of this study.

Intramural and Adapted-Germ Cell Neoplasia In situ

Germ cell neoplasia in situ emerges as a precursor lesion configuring type II germ cell tumours as testicular seminoma or post-pubertal non-seminomatous testicular germ cell tumours. Lesion is comprised of neoplastic gonocyte-like cells, latent totipotent or naive germ cells with developmental potential situated within ‘spermatogonial niche’ of seminiferous tubules. Germ cell neoplasia in situ delineates an increased incidence with conditions as uncorrected cryptorchidism, ambiguous genitalia, infertility or preceding history of post-pubertal germ cell tumour within contralateral testis. Neoplasm demonstrates aneuploidy or polypoid genotype with additional chromosomal gains as is chromosome 12p upon commencement of neoplastic invasion. Neoplastic cells appear enlarged, atypical, gonocyte-like and are incorporated with abundant, clear cytoplasm, enlarged, hyper chromatic nuclei, coarse nuclear chromatin, angulated cellular margins and prominent nucleoli.

SYNCHRONOUS DIAGNOSIS OF TESTICULAR AND THYROID CANCER IN A YOUNG MALE.

Testicular cancer is the most common neoplasm in young males. The early diagnosis and the appropriate treatment make it a curable malignancy in over 90% of the patients, but 6% of the patients with testicular cancer develop a second, mostly treatment-related, malignancy in another primary site many years after the first diagnosis. The simultaneous appearance of a testicular tumor with another primary neoplasm is rarely described in the literature. Here is presented an interesting case of a coexisting non-seminomatous germ cell testicular tumor with a papillary thyroid carcinoma, which was detected early during post-treatment restaging of the testicular tumor. The synchronous presence of these two neoplasms might indicate a probable common pathogenetic background. As treatment-related oncogenesis is highly improbable in this case and the common environmental factors are not known yet, the interest is focused on genetic predisposition. Recent discoveries in molecular genetics show that the two neoplasms share common genetic alterations in the RAS and BRAF genes, which affect the significant signaling pathways. Interestingly, BRAF-V600E was positive in both primary malignancies in our individual.

Radiomics Analyses to Predict Histopathology in Patients with Metastatic Testicular Germ Cell Tumors before Post-Chemotherapy Retroperitoneal Lymph Node Dissection.

The identification of histopathology in metastatic non-seminomatous testicular germ cell tumors (TGCT) before post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) holds significant potential to reduce treatment-related morbidity in young patients, addressing an important survivorship concern. To explore this possibility, we conducted a study investigating the role of computed tomography (CT) radiomics models that integrate clinical predictors, enabling personalized prediction of histopathology in metastatic non-seminomatous TGCT patients prior to PC-RPLND. In this retrospective study, we included a cohort of 122 patients. Using dedicated radiomics software, we segmented the targets and extracted quantitative features from the CT images. Subsequently, we employed feature selection techniques and developed radiomics-based machine learning models to predict histological subtypes. To ensure the robustness of our procedure, we implemented a 5-fold cross-validation approach. When evaluating the models' performance, we measured metrics such as the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F-score. Our radiomics model based on the Support Vector Machine achieved an optimal average AUC of 0.945. The presented CT-based radiomics model can potentially serve as a non-invasive tool to predict histopathological outcomes, differentiating among fibrosis/necrosis, teratoma, and viable tumor in metastatic non-seminomatous TGCT before PC-RPLND. It has the potential to be considered a promising tool to mitigate the risk of over- or under-treatment in young patients, although multi-center validation is critical to confirm the clinical utility of the proposed radiomics workflow.

Quality of life assessment in testicular non-seminomatous germ cell tumour survivors.

Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors. A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL. A total of 55 cases and 100 controls were recruited. Cases had a median age of 32years (interquartile range, IQR 28-40years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5years from diagnosis. The median age of controls: 35years (IQR 28-43years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant. There is a detrimental impact of history of GCT in long term survivors of GCT.

Prediction of microdissection testicular sperm extraction outcomes of azoospermic patients post-chemotherapy using cyclophosphamide equivalent dose.

We determined the sperm retrieval rate in men with persistent azoospermia post-chemotherapy in relation to cyclophosphamide equivalent dose (CED), a unit for quantifying alkylating agent exposure. Medical records were retrospectively reviewed of 1098 patients diagnosed with non-obstructive azoospermia who had undergone microdissection testicular sperm extraction (mTESE) between January 2010 and 2021 at our institution. Twenty-three patients with a prior history of chemotherapy were included in the study. Oncological data, chemotherapy regime, and dosage were reviewed. The pretreatment hormone profile, CED, and mTESE outcomes were analyzed. Testicular spermatozoa were successfully retrieved from 11 patients (47%). The mean patient age was 37.3years (range, 27-41years), and mean time interval from chemotherapy to mTESE, 11.8years (range, 1-45years). Patients exposed to alkylating agents had significantly lower sperm retrieval rates than those not exposed to alkylating agents (1/9, 11% vs. 10/14, 71%, p = 0.009). No men with CED > 4000mg/m2 (n = 6) had viable sperm in the testes during mTESE. Moreover, patients diagnosed with testicular non-seminomatous germ cell tumors had a favorable sperm retrieval rate (67%) compared to patients with lymphoma (20%) or leukemia (33%). Patients with permanent azoospermia post-chemotherapy have a lower testicular sperm retrieval rate when the chemotherapy regimen included alkylating agents. In cases where patients have undergone more intensive gonadotoxic treatments, such as higher CED, the likelihood of successful sperm retrieval is low. It is advisable to counsel such patients using the CED model prior to considering surgical sperm retrieval.

Autoimmune Haemolytic Anaemia Associated with Testicular Non-seminomatous Germ Cell Tumour (NSGCT): A Unique Paraneoplastic Presentation

Paraneoplastic syndrome (PNS) is the rare manifestation of malignancy which presents as remote systemic features unrelated to direct tumour involvement. Often PNS can be the only presenting symptom of the cancer and may warrant search for underlying malignancy. Immune response against malignant cells sometimes cross reacts and destroys the normal cells. PNS can manifest at any point of time in course of malignancy, either it may presage diagnosis, or at relapse settings. Successful treatment of the malignancy is the key in managing PNS. Autoimmune haemolytic anaemia (AIHA) is a common presentation of haematological malignancy, but rarely reported with malignant solid tumours. We, hereby, illustrate a rare association of AIHA as PNS in a case of testicular non-seminomatous germ cell tumour and its management along with review of literature. To the best of our knowledge, this is the first such a case to be reported in the literature.

Relapse-free and overall survival in patients with non-seminomatous testicular germ cell tumours with teratoma-free primaries.

421 Background: Characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate. Methods: We performed a retrospective analysis including 557 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". Results: Of the eligible 557 patients with NSGCT, 237 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 320 (58%) were teratoma-free. Teratoma-containing primaries had a significantly higher clinical stage (p=0.002) and worse prognosis (p=0.051) compared to teratoma-free specimens. Lymph node metastasis were significantly larger before (4.5 vs 2.5cm; p&lt;0.001) and after chemotherapy (3.5 vs 2.5 cm; p&lt;0.001) in teratoma-containing primaries. Post-chemotherapy retroperitoneal lymph node dissection was performed in 57% of all patients. As teratoma-containing specimens revealed a significantly lower number of complete responses after chemotherapy, PC-PRLND was more often performed, with teratomatous elements being more often present in the PC-RPLND specimens compared to non-teratoma containing primaries. Kaplan-Meier estimates revealed that 19% of all patients relapsed during a median follow-up of 56 months [29-112] with a median time to relapse of 10 months. Teratoma-containing had a significantly lower relapse-free survival (RFS) compared to teratoma-free NSGCT (relapse rate 24% vs 16%, p=0.020). 8% (45/533) of all patients died due to their disease. There was no difference regarding the tumour-specific survival between teratoma-containing NSGCT and teratoma-free NSGCT when looking at the entire cohort of patients (8% vs. 9%, p=0.563), however median overall survival was not reached. Conclusions: In our study, NSGCT patients with teratoma-containing primaries showed a significantly higher clinical stage and worse prognosis at time of presentation compared to teratoma-free primaries. Furthermore, patients with teratoma-containing primaries showed a significantly worse relapse-free survival. Consequently, treating physicians should be aware of these patients portending a dismal prognosis and the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

Non-seminomatous testicular germ cell tumours with teratoma-free primaries exhibit a superior early relapse-free survival

Non-seminomatous testicular germ cell tumours with teratoma-free primaries exhibit a superior early relapse-free survival

Integrated Microarray-Based Data Analysis of miRNA Expression Profiles: Identification of Novel Biomarkers of Cisplatin-Resistance in Testicular Germ Cell Tumours.

Testicular germ cell tumours (TGCTs) are the most common solid malignancy among young men, and their incidence is still increasing. Despite good curability with cisplatin (CDDP)-based chemotherapy, about 10% of TGCTs are non-responsive and show a chemoresistant phenotype. To further increase TGCT curability, better prediction of risk of relapse and early detection of refractory cases is needed. Therefore, to diagnose this malignancy more precisely, stratify patients more accurately and improve decision-making on treatment modality, new biomarkers are still required. Numerous studies showed association of differential expressions of microRNAs (miRNAs) with cancer. Using microarray analysis followed by RT-qPCR validation, we identified specific miRNA expression patterns that discriminate chemoresistant phenotypes in TGCTs. Comparing CDDP-resistant vs. -sensitive TGCT cell lines, we identified miR-218-5p, miR-31-5p, miR-125b-5p, miR-27b-3p, miR-199a-5p, miR-214-3p, let-7a and miR-517a-3p as significantly up-regulated and miR-374b-5p, miR-378a-3p, miR-20b-5p and miR-30e-3p as significantly down-regulated. In patient tumour samples, we observed the highest median values of relative expression of miR-218-5p, miR-31-5p, miR-375-5p and miR-517a-3p, but also miR-20b-5p and miR-378a-3p, in metastatic tumour samples when compared with primary tumour or control samples. In TGCT patient plasma samples, we detected increased expression of miR-218-5p, miR-31-5p, miR-517a-3p and miR-375-5p when compared to healthy individuals. We propose that miR-218-5p, miR-31-5p, miR-375-5p, miR-517-3p, miR-20b-5p and miR-378a-3p represent a new panel of biomarkers for better prediction of chemoresistance and more aggressive phenotypes potentially underlying metastatic spread in non-seminomatous TGCTs. In addition, we provide predictions of the targets and functional and regulatory networks of selected miRNAs.

Case Report: Adult Pure Yolk Sac Tumor of the Testis

Yolk sac tumor is a non-seminomatous testicular germ cell tumor rarely found in adults. It is an extra-embryonic differentiated tumor. It reproduces structures evocative of the yolk sac in humans. We report the clinical case of a 37-year-old patient, with no previous history, who is followed up for a tumor of the left testicle revealed by an increase in size and induration of the testicle. The left orchiectomy, performed through an inguinal approach, allowed us to retain the diagnosis of pure yolk sac tumor on anatomical and immunohistochemical examination. The evolution was marked during the surveillance by a relapse requiring a systemic treatment.

515P Prognostic significance of elevated serum tumor markers (STM) after the first cycle of chemotherapy in patients with intermediate and poor risk non seminomatous testicular germ cell tumors (NSGCT)

Testicular GCT is an extremely chemosensitive malignancy and has excellent survival rates. We looked at the prognostic significance of raised STMs after the first cycle of chemotherapy in men with intermediate and poor risk NSGCT.

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Clinical characteristics of testicular non-seminomatous germ cell tumor from West China: a 10-year experience.

Prognostic significance of raised serum tumor markers (STM) after 2 cycles of chemotherapy in men with intermediate- and poor-risk non-seminomatous testicular germ cell tumors (NSGCT) treated at a single-centre in India.

5036 Background: Testicular GCT is a rare malignancy, with excellent outcomes. However, approximately one-fourth of intermediate risk and half of the patients with poor risk disease succumb to recurrent GCT. We looked at the prognostic significance of raised serum tumor markers after 2 cycles of chemotherapy in patients with poor risk GCT. Methods: This is a chart-review based retrospective analysis of patients with intermediate and poor risk NSGCT diagnosed and treated at a tertiary care centre in New Delhi, India from 2015-2021. Risk categories were defined as per the International Germ Cell Cancer Collaborative Group. Multivariable Cox regression models were constructed to analyse the prognostic impact of normal STM at the end of second cycle of chemotherapy on overall survival (OS) and relapse free survival (RFS), while adjusted for measured confounders. Results: A total of 312 patients were identified with testicular NSGCT, of whom 109 were intermediate (n = 48, 44%) and poor risk (n = 61, 56%). The median age at diagnosis was 27 (interquartile range, 21-34) years. ECOG PS of patients was 0-1 in 51% and 2-4 in 49%, and poor risk patients were more likely to have a poor ECOG PS at diagnosis (70% vs 30%, P &lt; 0.001). First-line chemotherapy was BEP in 86% patients and VIP in the remaining 14%, and surgery for residual disease was performed in 22%. Overall, 35% patients had normal STM after 2 cycles of chemotherapy, and patients with intermediate risk were likely to achieve normal STM at this time-point (50% vs 23%). At a median follow-up of 62 months, the 5-year RFS rate was 62% (poor risk 52% and intermediate risk 78%), and OS rate was 68% (58% and 80%, respectively). Men with normal STM after 2 cycles chemotherapy had a better RFS (hazard ratio [HR], 0.70; 95% confidence interval 0.48-0.81; P &lt; 0.001) and OS (HR,0.82; 95% CI 0.61-0.99; P = 0.04). After adjusting for risk category, and ECOG PS in a multivariable Cox regression model, patients with normal STM at the end of 2 cycles of chemo continued to have better outcomes (adjusted HR for RFS, 0.78; 95% CI, 0.77-0.89; P = 0.03, and adjusted HR for OS, 0.92; 95% CI,0.81-0.99; P = 0.05). Intermediate risk NSGCT and good ECOG PS also predicted better RFS and OS. Conclusions: Patients with NSGCT whose STMs do not normalize after 2 cycles of chemotherapy have worse RFS and OS compared to those with normal STM at this time-point. Further clinical trials will be needed to study the role of escalation or switch of chemotherapy in this subset of population.

Structure of residual metastases in patients with advanced testicular non-seminomatous germ cell tumors and incomplete serological and radiological response to chemotherapy

Objective: to analyze histological structure and identify predictors of detecting malignant non-seminoma in residual tumor masses obtained from patients with testicular non-seminomatous germ cell tumors (TNSGCTs) who had not achieved complete serological and radiological response to chemotherapy (CT).Materials and methods. This study included 96 out of 703 patients with TNSGCTs (13.7 %) operated on in N.N. Blokhin National Medical Research Center of Oncology. The inclusion criteria were as follows: verified advanced TNSGCT, elevated levels of alpha-fetoprotein and/or chorionic gonadotropin at the moment of CT initiation, at least 3 completed courses of first-line or second-line platinum-based CT, residual tumor foci after CT visualized with radiological methods, alpha-fetoprotein &gt;7.29 IU/mL or chorionic gonadotropin &gt;5 mIU/mL 3 weeks after the initiation of the last CT course, and surgery after CT. Histological examination of the primary tumors demonstrated that they contained elements of seminoma (n = 14; 14.6 %), teratoma (n = 29; 30.2 %), choriocarcinoma in (n = 23; 23.9 %), embryonal carcinoma (n = 45; 46.9 %), and yolk sac (n = 18; 18.8 %). All study participants received first-line CT; 58 of them (60.4 %) also received second-line CT. All patients underwent surgery after CT, including retroperitoneal lymph node dissection (RPLND) (n = 96; 100 %) and excision of extra-retroperitoneal lesions (n = 8; 8.3 %).Results. Histological examination of excised retroperitoneal masses showed that they contained areas of necrosis and fibrosis (n = 25; 26.0 %), teratoma (n = 29; 30.2 %), and viable malignant non-seminoma (n = 42; 43.8 %). There was a strong positive correlation between the existence of residual malignant non-seminomatous components in retroperitoneal masses and presence of choriocarcinoma (r = 0.300; р = 0.004), as well as the absence of embryonal carcinoma in the primary tumor (r = –0.300; р = 0.004), invasion of retroperitoneal metastases into major vessels and/or adjacent organs (r = 0.243; р = 0.017), and second-line CT prior to RPLND (r = 0.413; р &lt;0.0001). Patients having ≥3 risk factors were significantly more likely to have residual malignant non-seminoma in retroperitoneal masses than patients who had 0–2 risk factors (73.5 % vs 27.3 %; р &lt;0.0001). Excised residual extra-retroperitoneal masses contained areas of necrosis and fibrosis (n = 3; 37.5 %), teratoma (n = 1; 12.5 %), and malignant non-seminoma (n = 4; 62.5 %). Concordant structure of retroperitoneal and extra-retroperitoneal lesions was observed in 4 patients (50.0 %).Conclusion. Malignant non-seminomas were detected in 43.8 % of retroperitoneal and 62.5 % of extra-retroperitoneal residual tumorsremoved after CT in patients with advanced TNSGCTs and incomplete serological and radiological response. Discordant structure of metastases at different locations was observed in 50 % of patients. Our finding can be used to select candidates for surgical excision of residual tumors among these patients.