Pure Teratoma Research Articles

Diagnostic incidence and pitfalls of rete testis hyperplasia and hyaline globules in a multi-institutional study of 348 testicular germ cell tumors.

The concept of rete hyperplasia with hyaline globules simulating testicular yolk sac tumor was first reported in a mostly retrospective review over 30 years ago. Nonetheless, we continue to encounter examples where this scenario resulted in misdiagnosis. Herein, we sought to investigate the incidence of rete hyperplasia/hyaline globules in germ cell tumors and their associated subtypes and hypothesize an etiology. A consecutive series of 348 germ cell tumor orchiectomies was evaluated for the presence of rete hyperplasia and hyaline globules, with clinicopathologic features recorded. The incidence of rete hyperplasia and/or hyaline globules in our cohort was 30%, with 56% of specimens with rete hyperplasia containing concomitant hyaline globules. Hyaline globules were more often identified in specimens with nonfocal rete hyperplasia (78%) vs focal rete hyperplasia (22%). Absence of a yolk sac tumor component was seen in over half (61%) of orchiectomies with concurrent rete hyperplasia/hyaline globules (n = 105), inclusive of tumors with "pure" subtypes (ie, pure seminoma, pure teratoma, or pure embryonal carcinoma). Of these 105 specimens, rete invasion was seen in only 48%; notably, Paneth cell-like metaplasia was identified in efferent ductules/epididymis in 13%. Rete hyperplasia and hyaline globules are not uncommon findings in the setting of germ cell tumors (including occurrences in various pure/mixed germ cell tumors) and can show striking overlap with yolk sac tumor. We hypothesize that these histologic pitfalls evolve secondary to testicular obstruction by the tumor mass. Recognition of and distinguishing this morphologic mimicry is fundamental to guide appropriate clinical management.

Phenotype and gene signature of testicular tumors in 129.MOLF-Chr19 mice resemble human teratomas.

Testicular germ cell tumor (TGCT) is the most common type of tumor in young men. Type II germ cell tumors including postpubertal-type teratomas are derived from the germ cell neoplasia in situ (GCNIS), whereas prepubertal-type teratomas arise independently of the GCNIS. The consomic mouse strain 129.MOLF-Chr19 (M19) is a suitable murine model of such tumors, but its characterization remains incomplete. Here, we interrogated the suitability of testicular tumors in M19 mice as a model of human TGCT by analyzing their histological features and gene expression signature. Testes collected from M19 mice of different ages were categorized by macroscopic appearance based on size and the degree of suspected tumorigenesis. Histological sections from selected tumors were stained with Hematoxylin and Eosin, and expression of genes associated with tumorigenesis was determined in frozen tissue samples from a large range of tumors of different subclasses using RT-qPCR and Fluidigm Dynamic Arrays. Macroscopically, testicular specimens appeared very heterogeneous concerning size and signs indicating the presence of a tumor. Histological analysis confirmed the development of teratomas with areas of cells corresponding to all three germ cell layers. Gene expression analyses indicated upregulation of markers related to proliferation, vascular invasive potential and pluripotency, and revealed a strong correlation of gene expression with tumor size and a significant intercorrelation of individual genes. TGCT in M19 mice is reminiscent of human testicular teratomas presenting with areas of cells derived from all germ layers and showing a typical gene signature. We thus confirm that these mice can serve as a suitable murine model of pure teratomas for preclinical research.

Primary intracranial germ cell tumors in adolescents and adults: Results of an international, multicenter, retrospective cohort study.

2061 Background: Primary Intracranial Germ Cell Tumors (iGCT) are rare. Previous prospective and retrospective studies mainly included pediatric patients (pts) with a median age of 10-14 years. The aim of this retrospective analysis was to evaluate characteristics, treatment and outcome of adolescents and adults with iGCT. Methods: Data were collected from 10 institutions in Germany and Switzerland. Pts aged >/= 16 years at first diagnosis or at relapse with a primary iGCT were included. Objective responses were evaluated by local investigators. Statistics (Cox proportional hazard model, progression-free survival (PFS) and overall survival (OS) analyzed by Kaplan-Meier method) were performed with SPSS v29. Results: We identified 75 pts (92.0% male) with a median age of 23 years (range 16-60, 94.7% >/= 18 years). At first diagnosis, histology was pure germinoma in 70.7%, pure teratoma in 10.7%, other non-germinomatous GCT (NGGCT) in 13.3%, unknown in 5.3% of pts. Localized, bifocal, and metastatic disease was found in 72.0, 6.7, and 21.3% of pts. As part of their first line (1L) treatment, 69.3%, 80.0%, and 62.7% received surgery, radiotherapy, and chemotherapy, respectively. High dose chemotherapy/ autologous stem cell transplantation (HDCT/ASCT) was part of 1L treatment in n=3 pts with NGGCT. Trimodal and bimodal treatment was performed in 48.0% and 32.0% of pts. Response to 1L therapy was complete remission (CR) in 61.3%, partial remission tumor marker negative (PRm-) in 16.0%, PRm+ in 4.0%, PR with tumor marker status unknown in 4.0%, progressive disease (PD) in 2.7%, and unknown in 12.0%. Relapse occurred in 13/75 pts (17.3%) with unknown histology (n=4), teratoma (n=2), other NGGCT (n=4), and germinoma (n=3). In 2 pts. in whom germinoma was diagnosed at time of first diagnosis, at time of recurrence PNET and Yolk sac tumor were histologically proven. Median time to relapse was 19.0 months (mo.; range 3-223). HDCT/ASCT as salvage treatment was performed in 5 pts with NGGCT and in one pt with germinoma as 2L (n=5) or 3L (n=1). NGGCT histology was associated with increased risk for recurrence or death (p=0.012 and 0.039).3-year PFS was 90.7% (germinoma: 98.1%, NGGCT: 73.9%) and 5-year OS was 92.0% (germinoma: 98.1%; NGGCT: 78.3%). Median follow-up time was 60 mo (range 0-339). Conclusions: Disease characteristics, treatment and outcomes of adolescent/ adult iGCT pts are comparable to those reported in pediatric pts. High cure rates are achieved in pts with pure germinoma and current treatment concepts. In pts with NGGCT further investigation is needed to improve survival outcomes.

Diffusion-weighted imaging in pediatric extracranial germ cell tumors.

Germ cell tumors (GCTs) comprise a rare and heterogeneous group of neoplasms presenting different clinical and histological characteristics, leading to a challenging scenario in clinical practice. Diffusion-weighted imaging (DWI) has been suggested as an indirect marker of tumor density and cellularity and could be used to monitor therapeutic response. However, its role in pediatric GCTs needs to be clarified. Here, we evaluated the features of DWI in pediatric extracranial GCTs in a reference Brazilian institution. We included 43 pediatric patients with primary GCTs treated between 2008 and 2022 in Hospital de Amor de Barretos. The patients' MRI images included T1-weighted without contrast, T2-weighted, DWI and apparent diffusion coefficient (ADC) maps. DWI was evaluated in the section that exhibited the greatest restricted diffusion in the largest hypersignal area of the image. The lowest ADC value was determined to define the region of interest (ROI). We used a small ROI, avoiding necrotic, adipose tissue, noisy or nonenhancing lesion voxels as recommended. ROI determination was established by visual inspection by two radiologists in accordance. We used two values of b (b = 50 mm2/s or b = 800) for ADC values. The highest mean ADC (mADC) value was observed in pure teratomas (1,403.50 ± 161.76 x10-3 mm2/s; mean ± SD) compared to other histologies (yolk sac, mixed teratoma, dysgerminoma and mixed GCT) of GCT (p<0.001). Furthermore, ROC analysis determined a cutoff mADC value of 1,179.00 x 10-3 mm2/s that differentiated pure teratomas from the other GCT histologies with a sensitivity of 95.8% and a specificity of 92.9% (AUC = 0.979; p<0.01). A significant increase in mADC was observed for malignant GCTs in treatment (1,197.00 ± 372.00 mm2/s; p<0.001) compared to that exhibited at the time of diagnosis (780.00 ± 168.00 mm2/s; mean ± SD. Our findings suggest that mADC assessment could be used as a tool to distinguish pure teratomas from malignant CGT histologies at diagnosis. Additionally, we demonstrated reasonable evidence that it could be used as a complementary tool to monitor treatment response in patients with malignant GCT.

Evaluation of a miRNA-371a-3p Assay for Predicting Final Histopathology in Patients Undergoing Primary Nerve-sparing Retroperitoneal Lymphadenectomy for Stage IIA/B Seminoma or Nonseminoma

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 summaryOur 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.

MP50-06 SURVIVAL OF TESTICULAR PURE TERATOMA VS. MIXED GERM CELL TUMOR PATIENTS ACROSS ALL STAGES

MP50-06 SURVIVAL OF TESTICULAR PURE TERATOMA VS. MIXED GERM CELL TUMOR PATIENTS ACROSS ALL STAGES

MP50-16 ONCOLOGICAL OUTCOMES FOLLOWING ROBOTIC POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR TESTICULAR CANCER: A WORLDWIDE MULTICENTER STUDY

You have accessJournal of UrologyCME1 Apr 2023MP50-16 ONCOLOGICAL OUTCOMES FOLLOWING ROBOTIC POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR TESTICULAR CANCER: A WORLDWIDE MULTICENTER STUDY Alireza Ghoreifi, Anirban Mitra, Ashish Khanna, Jordan Rich, George McClintock, Fady Baky, Zachary Mcdowell, Matthew Ho, Jacob Roberts, Farshad Sheybaee Moghaddam, Taseen Haque, Inderbir Gill, Scott Eggener, James Porter, Nariman Ahmadi, Reza Mehrazin, John Sfakianos, Aditya Bagrodia, Sudhir Rawal, John Ward, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi More articles by this author , Anirban MitraAnirban Mitra More articles by this author , Ashish KhannaAshish Khanna More articles by this author , Jordan RichJordan Rich More articles by this author , George McClintockGeorge McClintock More articles by this author , Fady BakyFady Baky More articles by this author , Zachary McdowellZachary Mcdowell More articles by this author , Matthew HoMatthew Ho More articles by this author , Jacob RobertsJacob Roberts More articles by this author , Farshad Sheybaee MoghaddamFarshad Sheybaee Moghaddam More articles by this author , Taseen HaqueTaseen Haque More articles by this author , Inderbir GillInderbir Gill More articles by this author , Scott EggenerScott Eggener More articles by this author , James PorterJames Porter More articles by this author , Nariman AhmadiNariman Ahmadi More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , John SfakianosJohn Sfakianos More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Sudhir RawalSudhir Rawal More articles by this author , John WardJohn Ward More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The feasibility and safety of robotic approach for post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) has been previously shown by our group. The aim of this study is to evaluate the oncological outcomes of robotic PC-RPLND. METHODS: In this retrospective study, we included patients who underwent robotic PC-RPLND at nine academic centers across the world between 2011 and 2022. Patients’ characteristics, pathological findings, and oncological outcomes were reviewed. RESULTS: A total of 137 patients with a median age of 29 (IQR 25, 36) years were included. The baseline features and clinicopathological findings are shown in Table 1. BEP (bleomycin, etoposide, cisplatin) was the main chemotherapy regimen (80%) and 12 patients (9%) received salvage chemotherapy. Twelve cases (9%) were electively converted to open. Median estimated blood loss, operative time, and length of hospital stay were 100 mL, 5 hours, and 2 days, respectively. Final pathology revealed necrosis/fibrosis in 59 (43%), pure teratoma in 64 (47%), and viable germ cell tumor in 14 (10%) patients. Among patients with residual viable tumor, those with pN2,3 non-seminoma received chemotherapy and the others were followed closely. With a median follow-up of 21 (IQR 8, 49) months, seven patients (5%) had disease recurrence, of whom 3 (2%) were in-field (Table 2). 2-year recurrence free survival was 93%. Median time to recurrence was 11 months. No port-site recurrence or carcinomatosis was identified. Two (1.5%) cancer-related deaths were recorded. CONCLUSIONS: At centers with expertise in testicular cancer and minimally invasive surgery, in appropriately selected patients robotic PC-RPLND is associated with comparable short-term oncological outcomes to the open approach. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e691 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Anirban Mitra More articles by this author Ashish Khanna More articles by this author Jordan Rich More articles by this author George McClintock More articles by this author Fady Baky More articles by this author Zachary Mcdowell More articles by this author Matthew Ho More articles by this author Jacob Roberts More articles by this author Farshad Sheybaee Moghaddam More articles by this author Taseen Haque More articles by this author Inderbir Gill More articles by this author Scott Eggener More articles by this author James Porter More articles by this author Nariman Ahmadi More articles by this author Reza Mehrazin More articles by this author John Sfakianos More articles by this author Aditya Bagrodia More articles by this author Sudhir Rawal More articles by this author John Ward More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement PDF downloadLoading ...

Survival of testicular pure teratoma vs. mixed germ cell tumor patients across all stages

Survival of testicular pure teratoma vs. mixed germ cell tumor patients across all stages

Survival of Testicular Pure Teratoma vs. Mixed Germ Cell Tumor Patients in Primary Tumor Specimens across All Stages.

We aimed to test for survival differences between testicular pure teratoma vs. mixed germ cell tumor (GCT) patients in a stage-specific fashion. Pure teratoma and mixed GCT in primary tumor specimens were identified within the Surveillance, Epidemiology, and End Results database (2004-2019). Kaplan-Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models were used. Of 9049 patients, 299 (3%) had pure teratoma. In stage I, II and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 91.6 vs. 97.2%, p < 0.001; stage II: 100 vs. 95.9%, p < 0.001; stage III: 66.8 vs. 77.8%, p = 0.021). In stage I, survival differences originated from higher OCM (6.4 vs. 1.2%; p < 0.001). Conversely in stage III, survival differences originated from higher CSM (29.4 vs. 19.0%; p = 0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 4.83; p < 0.01). Conversely, in stage III, in multivariable CRR models, pure teratoma was associated with higher CSM (HR: 1.92; p = 0.04). In pure teratoma, survival disadvantage in stage I patients relates to OCM. Survival disadvantage in stage III pure teratoma originates from higher CSM.

Pathologic findings and clinical outcomes in patients who required neoadjuvant chemotherapy before orchiectomy for testicular germ cell tumors

Treatment for testicular germ cell tumors (GCTs) includes orchiectomy followed potentially by adjuvant chemotherapy. Rarely, patients with testicular GCT have significant metastatic disease, requiring neoadjuvant chemotherapy before orchiectomy. We investigated the pathologic findings and clinical outcomes in patients who underwent neoadjuvant chemotherapy before orchiectomy for testicular GCT. We identified 45 patients with a mean age of 34 years (range, 15-66 years). Orchiectomy findings included pure teratoma (n=23), no residual tumor (n=13), mixed GCT (n=5), pure seminoma (n=2), pure yolk sac tumor (YST) (n=1), and pure germ cell neoplasia in situ(n=1). Cancer-specific death occurred in 4 of 45patients (9%). Seventeen of 45patients (38%) experienced disease progression after initial chemotherapy. Eleven of 45patients (24%) underwent salvage chemotherapy. Retroperitoneal lymph nodes were the most common site of metastases followed by lung. Overall, the most common type of tumor found in metastases was YST (12/45, 27%) and teratoma (11/45, 24%). Of the 23 patients with residual pure teratoma in the testis, 9(39%) had disease recurrence and/or progression and 3(13%) died. In the metastases of these patients, nonteratoma GCT was found in 17 of 23patients (74%). Nine of 45patients (20%) had residual testicular nonteratoma GCT. Of the 9 patients, 6 (67%) had disease recurrence and/or progression and 1 (11%) died. Patients with no residual testicular disease (ypT0) had a lower risk of disease recurrence and/or progression (P=.046) and had no deaths. In patients who have undergone neoadjuvant chemotherapy for testicular GCT, the orchiectomy histology often does not correlate with the histology of metastases. No residual testicular disease indicates a better prognosis in these patients.

Primary Retroperitoneal Lymph Node Dissection for Patients With Pathologic Stage II Nonseminomatous Germ Cell Tumor-N1, N2, and N3 Disease: Is Adjuvant Chemotherapy Necessary?

According to National Comprehensive Cancer Network guidelines, adjuvant chemotherapy (AC) has been advocated after primary retroperitoneal lymph node dissection (RPLND) to reduce the risk of relapse in pathologic nodal (pN) stage pN2 or pN3, whereas surveillance is preferred for pN1. We sought to explore the oncologic efficacy of primary RPLND alone for pathologic stage II in nonseminomatous germ cell tumors (NSGCTs) to reduce overtreatment with chemotherapy. Patients with pathologic stage II NSGCT after primary RPLND between 2007 and 2017 were identified. Patients were excluded for elevated preoperative serum tumor markers, receipt of AC, or if pure teratoma or primitive neuroectodermal tumor elements were found in the retroperitoneal pathology. We identified 117 patients with active NSGCT in the retroperitoneum after primary RPLND. We excluded seven patients who lacked meaningful follow-up and 13 patients who received AC. There were 97 patients treated with RPLND alone: 41 pN1, 46 pN2, and 10 pN3. In total, 77 of 97 patients had not recurred after a median follow-up time of 52 months. The 2-year recurrence-free survival (RFS) was 80.3%, and the 5-year RFS was 79%. No differences in RFS were noted among nodal stage-pN1, pN2, and pN3-on Kaplan-Meier analysis. Lymphovascular invasion in the orchiectomy specimen, a high-risk pathologic feature, was also predictive of recurrence after primary RPLND. All 20 patients who recurred were treated with first-line chemotherapy and remained continuously disease free. Most men with pathologic stage II disease treated with surgery alone in our series never experienced a recurrence. We did not observe a difference in recurrences between patients with pN1 and pN2. The recommendation for AC for pN2 disease may be overtreatment in most patients.

Outcomes and prognostic variables of extracranial germ cell tumors in children and adolescents treated over a decade: A developing world perspective.

The purpose of this single-center study was to analyze the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multimodality regimen. Retrospective study of children (<18years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10years (January 2009 to December 2018) treated on a uniform institution-based protocol consisting of both cisplatin- and carboplatin-based regimens. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk [LR]); stage IV ovarian, stage III-IV extragonadal GCTs received six cycles of chemotherapy (high risk [HR]), and the remaining received four cycles of chemotherapy (intermediate risk [IR]). A total of 297 children were treated with a female:male ratio of 1.72:1 and median age of 4years. Forty-three children had pure teratomas. Gonadal GCTs (N=180) were more common than extragonadal GCTs (N=117) with ovary as primary site in 128 children (43%) and sacrococcygeal site being the commonest extragonadal location (N=41; 14%). LR, IR, and HR disease were noted in 60 (20.2%), 125 (42%), and 112 (37.8%) patients, respectively. Three-fourths of ovarian tumors and half of testicular tumors operated prior to presentation needed upstaging. Forty-one patients relapsed and 43 children expired (disease-related: 33; toxic deaths: 9; unknown: 1). The 5-year event-free survival (EFS)/overall survival (OS) of malignant GCT (n=254) was 72.50%/82.70%, respectively, with gonadal site (p=.001), LR and IR (p=.001) and nonmetastatic disease (p=.001) being favorable prognostic variables. The LR and IR GCTs in our cohort had an excellent outcome. A significant proportion of IR gonadal GCTs can be spared of systemic chemotherapy by adhering to strict surgical guidelines. In HR GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity, more so in a resource-limited setting.

MP46-02 REFINEMENT OF THE SERUM MIR-371A-3P TEST FOR THE DETECTION OF CHEMOTHERAPY-NAIVE MINIMAL RESIDUAL TESTICULAR CANCER

You have accessJournal of UrologyCME1 May 2022MP46-02 REFINEMENT OF THE SERUM MIR-371A-3P TEST FOR THE DETECTION OF CHEMOTHERAPY-NAIVE MINIMAL RESIDUAL TESTICULAR CANCER John T. Lafin, Armon Amini, Bendu Konneh, Anna Savelyeva, Jin Piao, Michelle Nuno, Cinzia G. Scarpini, Jeffrey M. Howard, Thomas Gerald, Nicholas Coleman, Matthew J. Murray, A. Lindsay Frazier, James F. Amatruda, and Aditya Bagrodia John T. LafinJohn T. Lafin More articles by this author , Armon AminiArmon Amini More articles by this author , Bendu KonnehBendu Konneh More articles by this author , Anna SavelyevaAnna Savelyeva More articles by this author , Jin PiaoJin Piao More articles by this author , Michelle NunoMichelle Nuno More articles by this author , Cinzia G. ScarpiniCinzia G. Scarpini More articles by this author , Jeffrey M. HowardJeffrey M. Howard More articles by this author , Thomas GeraldThomas Gerald More articles by this author , Nicholas ColemanNicholas Coleman More articles by this author , Matthew J. MurrayMatthew J. Murray More articles by this author , A. Lindsay FrazierA. Lindsay Frazier More articles by this author , James F. AmatrudaJames F. Amatruda More articles by this author , and Aditya BagrodiaAditya Bagrodia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002612.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While critical for patient care, existing serum tumor markers exhibit middling performance for the detection of testicular germ cell tumors (GCTs). Serum miRNAs, particularly miR-371a-3p, are reported to have excellent performance characteristics in the pre-orchiectomy setting. However, the ability of miR-371a-3p to detect occult disease is understudied. We previously reported in a small cohort of patients that miR-371a-3p outperforms conventional markers in the context of chemotherapy-naïve minimal residual disease. Here, we further refine the assay and expand upon that experience. METHODS: We examined over 250 distinct runs to compare performance between classification based on Cq, normalized Cq (∆Cq), or relative quantification (RQ). We prospectively collected clinical information and pre-surgical serum samples from chemotherapy-naïve GCT patients undergoing primary retroperitoneal lymph node dissection (RPLND) at our institution. Patients were classified as “Control” (pure teratoma or no GCT) or “GCT”. RNA was extracted from these serum samples, and miR-371a-3p (target) and miR-30b-5p (reference gene) were detected by qPCR. Performance was assessed by calculation of sensitivity, specificity, and area under the ROC curve (AUC). RESULTS: Performance did not change appreciably when thresholding based on Cq, ∆Cq, or RQ. We therefore decided to move forward with analysis considering only Cq. We found that any given control sample will return a spurious positive result approximately 25% of the time, and estimated an indeterminate range of Cq 28-35. Repeating any indeterminate sample once improved overall performance. We then compared this updated process to a simple binary threshold in a cohort of patients with occult disease. 32 patients were enrolled in the study (15 Control, 17 GCT). 12 samples were indeterminate on first run, and 8 remained indeterminate on a second run, all of which harbored viable GCT or teratoma. Inclusion of a second run prevented 3 false positives, improving specificity from 86% to 100% and yielding a sensitivity of 92% and AUC of 0.96 (95% CI: 0.89-1). CONCLUSIONS: The use of Cq instead of RQ to classify results for the miR-371a-3p test would help to avoid unnecessary sample runs without injuring assay performance. In the context of chemotherapy-naïve minimal residual testicular cancer, consideration of an indeterminate range may improve the performance of the miR-371a-3p test. Source of Funding: This work was supported by funding from the Cancer Prevention Institute of Texas, St. Baldrick’s Consortium, the Rally Foundation, the Malignant Germ Cell International Consortium, and the Dedman Family Scholarship in Clinical Care © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e772 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information John T. Lafin More articles by this author Armon Amini More articles by this author Bendu Konneh More articles by this author Anna Savelyeva More articles by this author Jin Piao More articles by this author Michelle Nuno More articles by this author Cinzia G. Scarpini More articles by this author Jeffrey M. Howard More articles by this author Thomas Gerald More articles by this author Nicholas Coleman More articles by this author Matthew J. Murray More articles by this author A. Lindsay Frazier More articles by this author James F. Amatruda More articles by this author Aditya Bagrodia More articles by this author Expand All Advertisement PDF DownloadLoading ...

Chromosome 3p25.3 Gain Is Associated With Cisplatin Resistance and Is an Independent Predictor of Poor Outcome in Male Malignant Germ Cell Tumors.

PURPOSECisplatin is the main systemic treatment modality for male type II germ cell tumors (GCTs). Although generally very effective, 5%-10% of patients suffer from cisplatin-resistant disease. Identification of the driving mechanisms of resistance will enable improved risk stratification and development of alternative treatments.METHODSWe developed and characterized cisplatin-resistant GCT cell line models and compared their molecular characteristics with patient samples with cisplatin resistance and/or a poor clinical outcome. Subsequently, the association between the overlapping genetic features and clinical data was assessed. Finally, we used Cox regression to determine the prognostic relevance of these features within the currently used risk classification.RESULTSGain of chromosome 3p25.3 was detected in all cisplatin-resistant cell lines, and copy number of this region correlated with the level of resistance (R = 0.96, P = 1.5e-04). Gain of this region was detected at low frequencies in primary tumors and at higher frequencies in relapsed and/or cisplatin-resistant tumors. Chromosome 3p25.3 gain was associated with shorter progression-free survival and overall survival, with the strongest association observed in nonseminomas excluding pure teratomas. 3p25.3 gain was more frequently observed in tumors with yolk sac tumor histology and predicted adverse outcome independent of the International Germ Cell Cancer Collaborative Group risk classification and the presence of TP53/MDM2 alterations.CONCLUSIONOn the basis of both in vitro analyses and clinical data, we found 3p25.3 to be strongly associated with cisplatin resistance and poor clinical outcome in male type II GCTs. Using genomic profiling, 3p25.3 status could help to improve risk stratification in male patients with type II GCT. Further characterization of this locus and underlying mechanisms of resistance is warranted to guide development of novel treatment approaches for cisplatin-resistant disease.

Optimization of serum miR-371a-3p for the detection of chemotherapy-naïve minimal residual germ cell tumor.

423 Background: Currently used serum tumor markers exhibit middling sensitivity and specificity for the detection of germ cell tumors (GCTs). Circulating miRNAs, particularly miR-371a-3p, have exhibited strong performance characteristics in the pre-orchiectomy setting. However, the ability of miR-371a-3p to detect chemotherapy-naïve occult disease is less clear. We previously reported in a small cohort of patients that miR-371a-3p outperforms conventional markers in the context of chemotherapy-naïve minimal residual disease. Here, we expand upon that experience and further refine the assay, including the recommendation of an indeterminate range. Methods: We examined over 250 assays to compare performance between classification based on raw Cq, Cq normalized to miR-30b-5p (∆Cq), or relative quantification to normal serum (RQ). We prospectively collected pre-surgical serum samples and clinical information from GCT patients undergoing primary retroperitoneal lymph node dissection (RPLND) at our institution. Patients were classified based on histology as “Control” (pure teratoma or no GCT) or “GCT”. RNA was extracted from these samples, and miR-371a-3p (target) and miR-30b-5p (reference gene) were detected by qPCR. Performance was assessed by calculation of sensitivity, specificity, and area under the ROC curve (AUC). Results: Sensitivity, specificity, and AUC did not significantly change based on thresholding metric (Cq, ∆Cq, or RQ). We found a 25% chance that any given control sample would return a false positive result, and to combat this, estimated an indeterminate range of Cq 28-35. Repeating any indeterminate sample once improved performance. We then compared the performance of this updated process to a simple binary threshold in a cohort of patients with occult disease. 32 patients were enrolled in the study (15 Control, 17 GCT). 12 samples were indeterminate on first run (6 Control, 6 GCT). 8 remained indeterminate on a second run, all of which harbored teratoma or viable GCT. Inclusion of a second run prevented 3 false positives, improving specificity from 86% to 100% and yielding a sensitivity of 92% and AUC of 0.96 (95% CI: 0.89-1). Conclusions: The use of Cq instead of RQ to classify results for the miR-371a-3p test would eliminate the need for a normal sample in each run without injuring assay performance. In the context of chemotherapy-naïve minimal residual germ cell tumor, consideration of an indeterminate range may improve the performance of the miR-371a-3p test.

Association of nonseminomatous testicular germ cell tumors with teratoma-free primaries with disease relapse and overall survival.

422 Background: As the characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate, this study aims at evaluating recurrence-free and tumor-specific survival in this cohort of patients. Methods: We performed a retrospective analysis including 218 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". We analysed patient characteristics as well as follow-up of all included patients, being treated from 2000 to 2021. Results: Of the eligible 218 patients with NSGCT, 92 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 126 (58%) were teratoma-free. Kaplan-Meier estimates revealed that 28% of all patients relapsed during a median follow-up of 58 months [35-112] with a median time to relapse of 10 months. Teratoma-containing and teratoma-free NSGCT did not show a significant difference regarding the occurrence of relapse, however, teratoma-containing NSGCT had a significantly lower rate of early relapses ( &lt; 24 months) compared to teratoma-free NSGCT (57% vs. 82%, p = 0.035). 14% (30/218) of all patients died due to their disease with a median time to death of 15 months, however median overall survival was not reached. 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 (11% vs. 16%, p = 0.299). However, in the group of intermediate or poor IGCCCG prognosis patients, tumour-specific survival was significantly worse in patients teratoma-free NSGCT compared to teratoma-containing specimens (16% vs. 35%, p = 0.040). Furthermore, patients with intermediate or poor IGCCCG prognosis showed a higher tumour-related mortality in pure teratoma-free primaries compared to patients with pure teratoma in the orchiectomy specimens (28% vs. 14%, p = 0.070). Here, pure embryonal carcinoma showed the highest relative mortality (80%). Conclusions: In our study, NSGCT patients with teratoma-containing primaries showed a significantly lower number of early relapses as well as a reduced tumour specific survival in intermediate and poor prognosis patients compared to teratoma-free NSGCT. Especially pure embryonal carcinoma patients revealed the highest rate of mortality. Consequently, treating physicians should be aware of these patients portending a dismal prognosis.

MicroRNAs in Differentiation of Embryoid Bodies and the Teratoma Subtype of Testicular Cancer.

Testicular germ cell tumours (TGCTs) are the most frequent tumour type among young, adult men. TGCTs can be efficiently treated, but metastases of the teratoma subtype, for which there are no circulating biomarkers, represent a challenge. Global microRNA expression in teratoma tissue and embryoid bodies was assessed using next-generation sequencing. Levels of microRNAs identified as potential biomarkers were obtained from serum of patients with teratoma and matched healthy men. We identified miR-222-5p, miR-200a-5p, miR-196b-3p and miR-454-5p as biomarker candidates from the tumour tissue and embryoid body screening but the expression of these microRNAs was very low in serum and not statistically different between patients and controls. miR-375-3p was highly expressed, being highest in patients with teratoma (p=0.012) but the levels of expression in serum from these patients and healthy controls overlapped. miR-371a-3p was not expressed in serum from patients with pure teratoma, only in patients with mixed tumours. The microRNA profiles of the teratoma subtype of TGCT and embryoid bodies were obtained and assessed for candidate circulating biomarkers, but none with high sensitivity and specificity for teratoma were identified in our study. We conclude that neither the proposed teratoma marker miR-375-3p nor miR-371a-3p are suitable as circulating teratoma markers.

PD53-02 ONCOLOGIC EFFICACY OF PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION FOR PATIENTS WITH PATHOLOGIC N1, N2, AND N3 DISEASE

You have accessJournal of UrologyPenile & Testicular Cancer: Penile & Testicular Cancer II (PD53)1 Sep 2021PD53-02 ONCOLOGIC EFFICACY OF PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION FOR PATIENTS WITH PATHOLOGIC N1, N2, AND N3 DISEASE Sean Kern, Isamu Tachibana, Mohammad Mahmoud, Timothy Masterson, Nabil Adra, Richard Foster, Lawrence Einhorn, and Clint Cary Sean KernSean Kern More articles by this author , Isamu TachibanaIsamu Tachibana More articles by this author , Mohammad MahmoudMohammad Mahmoud More articles by this author , Timothy MastersonTimothy Masterson More articles by this author , Nabil AdraNabil Adra More articles by this author , Richard FosterRichard Foster More articles by this author , Lawrence EinhornLawrence Einhorn More articles by this author , and Clint CaryClint Cary More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002080.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Adjuvant chemotherapy (AC) has been advocated after primary retroperitoneal lymph node dissection (RPLND) to reduce the historical 50% risk of relapse in pN2/N3 patients, whereas surveillance is preferred for pN1 patients. We sought to explore the oncologic efficacy of primary RPLND alone in non-seminomatous germ cell tumors in an effort to reduce overtreatment with chemotherapy. METHODS: Patients with pathologic stage II germ cell tumor after primary RPLND between 2007-2017 were identified. Patients were excluded for elevated pre-operative serum tumor markers, receipt of adjuvant chemotherapy, or if pure teratoma or primitive neuro-ectodermal tumor elements were found in the retroperitoneum on pathology. RESULTS: We identified 106 patients to have active germ cell tumor in the retroperitoneum following primary RPLND. Fourteen patients received AC and were excluded from the analysis. There were 56.2% of patients with predominant (>50%) embryonal carcinoma in the orchiectomy specimen and 51% had lymphovascular invasion. Median follow up of the entire cohort was 51.5 months. There were 92 patients treated with RPLND alone of which 39 were pN1, 43 were pN2, and 10 were pN3. Seventy four of the 92 patients have not recurred; their pathologic N stages were 30 pN1, 37 pN2, and 7 pN3. The 5-year recurrence-free survival by pN stage was 85% pN1, 85% pN2, and 63% pN3, respectively (log-rank p-value 0.56, Fig 1). All 18 patients who recurred were treated with first line chemotherapy (usually BEPx3) and remain continuously disease free. Locations of recurrence include biochemical (2), pelvis (2), lung (5), mediastinum (1), suprahilar (1), contralateral/out of field (2), in-field (1 bilateral, 1 right modified, 1 left modified template). Additionally, 2 patients had simultaneous recurrences in the lung/suprahilar region and lung/contralateral retroperitoneum, respectively. No patient died of testicular cancer. CONCLUSIONS: The majority (80.5%) of men with pathologic stage II disease treated with surgery alone in our series never experienced a recurrence. Furthermore, we did not observe a difference in recurrences between pN1 and pN2 patients and thus recommending adjuvant chemotherapy for N2 disease may result in overtreatment in the majority. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e916-e916 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sean Kern More articles by this author Isamu Tachibana More articles by this author Mohammad Mahmoud More articles by this author Timothy Masterson More articles by this author Nabil Adra More articles by this author Richard Foster More articles by this author Lawrence Einhorn More articles by this author Clint Cary More articles by this author Expand All Advertisement Loading ...

Retroperitoneal Lymph Node Dissection Versus Surveillance for Adult Early Stage Pure Testicular Teratoma: A Nationwide Analysis.

Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.

Expression of programmed death ligand-1 (PD-L1) in metastatic and postchemotherapy viable testicular germ cell tumors

IntroductionChemotherapy for testicular germ cell tumors (GCT) is highly effective, with few patients who do not respond. Clinical studies to evaluated novel treatments are challenging given the rarity of these patients. Therefore, we sought to evaluate PD-L1 staining on metastatic and postchemotherapy viable testicular GCTs as a surrogate for potential benefit for immunotherapy targeting the PD-1/PD-L1 axis. MethodsEthics research committee approval for this retrospective study was obtained by four participating institutions (CHU de Québec, St. Joseph's Health Care, Halifax Health Science Centre, Johannes Gutenberg University). Patients with viable metastatic testicular GCTs pathology samples were included. Patients with pure teratoma were excluded. PD-L1 staining with the 22C3 clone was evaluated on samples with >100 viable tumor cells using the combined positive score (CPS). ResultsFrom 51 patients identified at participating institutions, 24 postchemotherapy and 18 chemotherapy-naive metastatic samples were available for PD-L1 staining, with 9 matched prechemotherapy samples and 7 matched orchiectomy pathology samples, respectively. The median CPS score was 55.6 (IQR 16–100) for all metastatic samples, 44.9 (IQR 13–100) for postchemotherapy metastatic samples, and 68.8 (IQR 38–100) for chemotherapy-naïve metastatic samples, with the median number of viable tumor cells at 545, 500, and 550, respectively. Differences were not significant between chemotherapy-naïve and postchemotherapy samples (P = 0.07), though among non-seminoma GCT metastatic samples, CPS scores were significantly lower postchemotherapy (P = 0.02). Significant differences among postchemotherapy metastatic tumors were also seen according to predominant subtype, with lower CPS scores for predominant yolk sac and higher values for predominant seminoma and choriocarcinoma. In 7 patients with matched specimens pre- and postchemotherapy, a significant increase in CPS was observed for seminoma (26.7 vs. 81.7, P = 0.045), but not nonseminoma GCTs. Comparing all chemotherapy naïve-samples, PD-L1 expression was higher in metastatic samples versus testicular samples (mean CPS 68.8 vs. 39.8, P = 0.02). This was also seen in matched chemotherapy-naïve samples (mean CPS 77.9 vs. 33.1, P = 0.01). ConclusionOur results suggest that most patients with refractory GCTs postchemotherapy will not benefit from PD-1/PD-L1 immunotherapy. However, the high PD-L1 expression in patients with predominant or pure seminoma post-chemotherapy suggests this may represent a subgroup for whom further trials may be considered.