Metastatic Nonseminomatous Germ Cell Tumors Research Articles

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.

A novel radiomics-miRNAs integrated model to predict the histopathology of residual retroperitoneal masses in metastatic nonseminomatous germ cell tumors.

A novel radiomics-miRNAs integrated model to predict the histopathology of residual retroperitoneal masses in metastatic nonseminomatous germ cell tumors.

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.

Resection of Residual Masses After Chemotherapy for Metastatic Nonseminomatous Germ Cell Tumors in Adolescents and Adults.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.Optimal treatment of patients with testicular germ cell tumors requires a coordinated multidisciplinary approach, so that surgery, chemotherapy, and, when appropriate, radiation therapy can be integrated into a coherent and comprehensive treatment plan. Nonseminomatous germ cell tumors (NSGCT) are often a mixture of teratoma and cancer (choriocarcinoma, embryonal carcinoma, seminoma, and/or yolk sac tumor). While the cancers are highly sensitive to and often cured by chemotherapy, teratoma is resistant to chemotherapy and radiation therapy and generally must be resected surgically to be successfully treated. Therefore, the standard of care for metastatic NSGCT is to resect all resectable residual masses after chemotherapy. If such resection reveals only teratoma and/or necrosis/fibrosis, then patients are put on a surveillance schedule to monitor for relapse. If viable cancer is found and there are positive margins or 10% or more of any of the residual masses consists of viable cancer, then two cycles of adjuvant chemotherapy should be considered.

Clinical outcomes in patients with post-chemotherapy residual non-retroperitoneal (RP) disease in non-seminomatous germ-cell tumors (NSGCT).

e17027 Background: In patients (pts) with metastatic NSGCT, the presence of teratoma in the primary tumor specimen or in the post-chemo RP lymph node dissection (RPLND) has previously been shown to have no impact on prognosis. We report clinical outcomes of pts based on pathology in primary tumor and from post-chemotherapy non-RP disease surgical resection. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT treated between 1990-2021 who completed first-line chemotherapy and had residual extra-RP disease in the absence of residual RP disease. Pts who had post-chemo non-RP surgical resection were included. Kaplan-meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Results: 131 pts met eligibility. Median age at diagnosis was 28.6 (range, 16.2-51.5). Primary site was testis in 130 pts (99%). Primary tumor predominant histology was embryonal (34.4%), mixed (26%), choriocarcinoma (14.5%), teratoma (11.5%), yolk sac (10.7%), seminoma (1.5%). Metastatic sites at diagnosis were lung (27.5%), brain (19.8%), RP (14.5%), liver (8.4%), mediastinal LN (7.6%), bone (7.6%). All pts with RP mets at diagnosis had normalization of RP nodes after chemo. All pts had surgical resection of non-RP disease. None had RPLND. IGCCCG risk was good in 56, intermediate in 23, and poor in 52 pts. Median pre-chemo AFP was 66.7 (0.9-467,000). hCG was 692 (0.5-500,000). First-line chemo was BEPX4 in 68, BEPX3 in 29, EPX4 in 10, VIPX4 in 8, and other in 16 pts. 76 pts (58%) had teratoma in the primary tumor. Median follow-up was 3.16yrs. 2-yr PFS for pts with teratoma in primary was 59% (95% CI 45-71) vs. 54% for pts without (95% CI 38-67); p = 0.42. 2-yr OS for pts with teratoma in primary was 85% (95% CI 73-92) vs. 70% for pts without (95% CI 54-81); p = 0.18. 2-yr PFS and OS based on pathology and location of non-RP site are listed in Table 1. Conclusions: The presence of teratoma in primary tumor and post-chemotherapy non-RP resections is not associated with worse PFS or OS in pts with metastatic NSGCT. [Table: see text]

MP50-15 TESTICULAR RADIOMICS CORRELATED WITH PATHOLOGY AT TIME OF POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR NON-SEMINOMATOUS GERM CELL TUMOR

You have accessJournal of UrologyCME1 Apr 2023MP50-15 TESTICULAR RADIOMICS CORRELATED WITH PATHOLOGY AT TIME OF POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR NON-SEMINOMATOUS GERM CELL TUMOR Nikit Venishetty, Jacob Taylor, Yin Xi, Jeffrey Howard, Yeeseng Ng, and Aditya Bagrodia Nikit VenishettyNikit Venishetty More articles by this author , Jacob TaylorJacob Taylor More articles by this author , Yin XiYin Xi More articles by this author , Jeffrey HowardJeffrey Howard More articles by this author , Yeeseng NgYeeseng Ng More articles by this author , and Aditya BagrodiaAditya Bagrodia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testicular germ cell tumors are the most commonly diagnosed malignancy in men aged 20 to 39 years old, as a third of patients will have metastatic disease on presentation. Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is performed to treat patients with metastatic non-seminomatous germ cell tumor (NSGCT). Although 50% of patients will viable GCT or teratoma, there is no accurate measurement to predict pre-operatively which patients will have residual disease after chemotherapy. Our aim was to use testicular radiomics data, a method that collects quantitative tumor imaging data from conventional imaging, to predict pathology after PC-RPLND. METHODS: Radiomics, clinical, and pathologic data were extracted from 45 patients with metastatic NSGCT undergoing PC-RPLND. An abdominal radiologist drew regions of interest (ROI) around metastatic notes, and PyRadiomics was used to extract first order, shape, and second order statistics from each ROI. T-Tests were performed to differentiate radiomics features between binary pathology type. P values were adjusted using the BH method to control false discovery rate. Python 3.7 and R 4.2.0 used for additional statistical analyses. RESULTS: There were 16 clinical stage II patients and 28 clinical stage III. 42% of patients had necrosis on PC-RPLND pathology, while 53% and 4% patients had teratoma and viable germ cell tumor, respectively. First order statistics mean, median, 90th percentile, and root mean squares were significant (Table 1). No significant differences was observed in other first order, shape, or texture features. We also show that the first order statistics above as significant, while the other radiomic statistics were not significant. CONCLUSIONS: Testicular radiomics is a tool that can help predict which patients with metastatic NSGCT are at higher risk of persistent disease after chemotherapy. We found relatively few first-order radiomic variables that were correlated with post-operative pathology. Results may have also been less predictive given small number of patients (4%) with residual GCT at time of RPLND. Further precision of extraction of the radiomics data may improve clinical decision-making in patients with metastatic NSGCT after chemotherapy prior to RPLND. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e690 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nikit Venishetty More articles by this author Jacob Taylor More articles by this author Yin Xi More articles by this author Jeffrey Howard More articles by this author Yeeseng Ng More articles by this author Aditya Bagrodia More articles by this author Expand All Advertisement PDF downloadLoading ...

Testicular radiomics correlated with pathology at time of post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous germ cell tumor.

413 Background: Testicular germ cell tumors are the most commonly diagnosed malignancy in men aged 20 to 39 years old. Up to a third of patients will have metastatic disease at presentation typically managed with upfront chemotherapy. For many patients with metastatic non-seminomatous germ cell tumor (NSGCT), post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is performed to further stage and treat residual disease in the retroperitoneum. Although 50% of patients will have viable GCT or teratoma, we do not have accurate tools to predict pre-operatively which patients will have residual disease after chemotherapy. Testicular radiomics is an emerging field that collects complex quantitative tumor imaging data from conventional imaging to aid in clinical decision making. Our aim was to use testicular radiomics data to predict pathology after PC-RPLND. Methods: We extracted radiomics data on 45 patients with metastatic NSGCT undergoing PC-RPLND from 2008-2019. Clinical and pathologic data were collected. Regions of interest (ROI) around metastatic nodes were drawn by a dedicated abdominal radiologist. PyRadiomics, an open-source imaging extraction software, was used to extract first order, shape, and second order statistics from each ROI. Multiple t-tests of testing difference in radiomic features between binary pathology type were performed. P values were adjusted using the BH method to control false discovery rate. Boxplot of features with adjusted p value &lt; 0.05 were shown. Radiomic feature extraction was done in python 3.7 and statistical analyses were done in R 4.2.0. Results: There were 16 (36%) clinical stage II patients and 28 (62%) clinical stage III. 19 (42%) patients had necrosis on PC-RPLND pathology, while 24 (53%) and 2 (4%) patients had teratoma and viable germ cell tumor, respectively. First order statistics mean, median, 90th percentile and root mean squares were significant. Strong correlations were observed between these four features and a lower signal was associated with positive pathology (Table). No significant difference was observed in other first order, shape, or texture features. Conclusions: Testicular radiomics is an emerging tool that has the potential to help predict which patients with metastatic NSGCT are at higher risk of persistent disease after chemotherapy. This study found relatively few first order radiomic data that were correlated with post-operative pathology. Further precision of extraction of the radiomics data may improve clinical decision-making in patients with metastatic NSGCT after chemotherapy prior to RPLND. [Table: see text]

Management of Residual Nonretroperitoneal Disease in Postchemotherapy Nonseminomatous Germ-Cell Tumors.

The majority of patients with advanced nonseminomatous germ-cell tumor are cured with combination chemotherapy and surgical resection of residual disease when appropriate. In patients with both retroperitoneal (RP) and non-RP postchemotherapy residual disease, management of the non-RP disease is typically guided by pathologic findings at the time of RP resection. There are limited data to help guide management decisions in patients with non-RP postchemotherapy residual disease alone. The prospectively maintained Indiana University testicular cancer database was queried for patients with metastatic nonseminomatous germ-cell tumor treated between 1990 and 2021 who had residual non-RP disease in the absence of residual RP disease after completing either first-line or salvage chemotherapy. One hundred twenty-nine patients met eligibility and were included in this analysis. Seventy-five patients had teratoma in the primary tumor site, while 54 did not. Of those with teratoma in the primary, 55% had at least one postchemotherapy non-RP surgical specimen with teratomatous elements compared with 17% of those without teratoma in the primary (P < .001). Of those without teratoma in the primary site, 56% had at least one postchemotherapy non-RP surgical specimen with active germ-cell tumor compared with 31% of those with teratoma in the primary (P = .0046). The presence of teratoma in the primary tumor site is associated with a higher rate of teratoma in postchemotherapy residual non-RP disease. Patients without teratoma in the primary tumor should still be considered for resection of residual postchemotherapy disease that could harbor teratoma or active germ-cell tumor.

Risk of residual cancer after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumour and International Germ Cell Cancer Cooperative Group intermediate/poor prognosis: A multi-institutional retrospective cohort study

IntroductionCurrent guidelines recommend surveillance in metastatic non-seminomatous germ cell tumour patients treated with first-line-chemotherapy and a complete clinical response (normalisation of serum tumour markers and residual masses <1 cm). However, this recommendation is based on a series including patients with good prognosis according to International Germ Cell Cancer Cooperative Group prognostic group (IGCCCG-PG). The aim of this study was to analyse the proportion of residual teratoma and survival among patients with intermediate/poor IGCCCG-PG and a complete clinical response after first-line-chemotherapy. Material & methodsThis is a retrospective study of men with intermediate/poor IGCCCG-PG, who had a complete clinical response after first-line chemotherapy. Patients were either followed by surveillance or treated with post-chemotherapy retroperitoneal lymph node dissection (pcRPLND). ResultsBetween 2009 and 2018, 143 men with intermediate (n = 83) or poor (n = 60) IGCCCG-PG were treated at 11 international centres. Among 33 patients treated with pcRPLND, the specimen showed teratoma and viable cancer in 16 (48%) and 4 (12%). During a median a 7-year follow-up, 20/110 (18%) patients managed with surveillance relapsed, of whom seven (6%) had a retroperitoneal-only relapse versus 2/33 patients managed with pcRPLND relapsed. No difference was observed regarding overall survival (OS) among men treated with pcRPLND or surveillance (5-year OS, 93% and 89%, p-value = 0.35). The median time-to-recurrence among men on surveillance was 1.3 years (range: 0.3–9.1), and the most common sites of relapses included retroperitoneum (11%), chest (5%), and bones (4%). ConclusionsWhile most men with intermediate/poor IGCCCG-PG harbour teratoma/cancer in the retroperitoneum despite a complete response to first-line-chemotherapy, only 6% managed with surveillance relapsed in the retroperitoneum. There was no significant difference in OS between the two groups.

O6 - Risk of residual teratoma after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumor and IGCCCG intermediate/poor prognosis: A multi-institutional retrospective cohort study

O6 - Risk of residual teratoma after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumor and IGCCCG intermediate/poor prognosis: A multi-institutional retrospective cohort study

Growing Teratoma Syndrome-A Clinicoradiological Series.

Context Growing teratoma syndrome (GTS) is a rare entity seen following chemotherapy for metastatic nonseminomatous germ cell tumors, characterized by increase in size of the metastatic deposits, with normal serum tumor markers. Aims In this article, we aim to describe the various clinicoradiological presentations of GTS treated at our center. Design All patients who satisfied the GTS criteria from 2001 to 2019 were included. Characteristic imaging appearances along with sites of primary lesion and metastatic disease, stage and risk stratification at diagnosis, details of chemotherapy, details of surgical treatment and histopathology, levels of tumor markers, serum β-human chorionic gonadotropin, lactate dehydrogenase, and alpha fetoprotein levels at baseline and at the end of all chemotherapy were analyzed. Results The significant radiological findings observed were an increase in the fat and cystic components and appearance of coarse calcifications within the lesions. Majority of the cases were male patients (87.5%) with testicular primaries and GTS transformation in nodal metastases being the most common occurrence (75%). All eight cases (100%) showed an increase in size and cystic component, whereas four out of eight cases (50%) had presence of internal septations and internal calcification. Conclusion Early recognition of this entity and clinical decision making through serial radiological imaging are of utmost importance as these growing deposits are resistant to chemotherapy and radiotherapy, with complete surgical excision being the only curative and definitive treatment option.

Surveillance after Complete Response to First-Line Chemotherapy in Patients with Metastatic Nonseminomatous Germ Cell Tumor.

The optimal management of patients with metastatic germ cell tumors who achieve a complete response (CR) after first-line chemotherapy remains unsettled. This study reports long-term outcomes of patients with metastatic germ cell tumor managed with surveillance after achieving a CR to first-line chemotherapy. Patients with metastatic nonseminomatous germ cell tumor treated at Indiana University between 1990 and 2017 who achieved a CR after first-line chemotherapy and were monitored with surveillance were retrospectively analyzed. CR was defined as normalization of tumor markers AFP and hCG, and no residual mass >1 cm in long axis. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Three hundred sixty-seven patients achieved a CR and were managed with surveillance. After a median followup of 4.97 years, 34 patients had disease progression. At most recent followup, 346 (94%) patients were alive with no evidence of disease, 10 patients (2.7%) died of their disease, 5 (1.4%) died of other causes and 6 (1.6%) were lost to followup. The estimated 2-year PFS was 91% (95% CI: 87%-94%) and 2-year OS was 98% (95% CI: 96%-99%). The estimated 2-year PFS by International Germ Cell Cancer Collaborative Group risk category was 92% for good vs 90% for intermediate vs 87% for poor risk (p=0.15), and the estimated 2-year OS was 99% for good vs 96% for intermediate vs 93% for poor risk disease (p=0.001). Patients with metastatic nonseminomatous germ cell tumor who achieve a CR after first-line chemotherapy can be observed. Most patients who relapse can be salvaged with surgery and/or chemotherapy.

Management of residual nonretroperitoneal disease in nonseminomatous germ-cell tumors (NSGCT).

5034 Background: The management of NSGCT patients (pts) with post-chemotherapy residual non-retroperitoneal disease (RP) remains unsettled. Decisions for surveillance vs surgical resection are commonly steered by pathology from retroperitoneal lymph node dissection (RPLND). Data is limited in pts who do not require RPLND (normal or normalized RP post-chemo). Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT who completed first-line chemotherapy and had residual extra-RP disease without residual RP disease. Pts with post-chemo non-RP surgical resection were included. Results: 134 pts met eligibility. Median age at diagnosis was 28.6 (range, 16.2-51.5). Primary tumor predominant histology was embryonal (35.1%), mixed (25.4%), seminoma (2.2%), yolk sac (9.7%), choriocarcinoma (15.7%), teratoma (11.2%). 76 pts (56.7%) had teratoma in the primary tumor. Metastatic sites at diagnosis were RP (15.7%), mediastinal LN (8.2%), lung (28.4%), liver (11.2%), bone (6.7%), brain (21.6%). Those with RP mets at diagnosis had normalization of RP nodes after chemo. IGCCCG risk was good in 57, intermediate in 21, and poor in 56 pts. Median pre-chemo AFP was 66 (0.9-467,000). hCG was 960.5 (0.5-1,300,000). First-line chemo was BEPX4 in 68, BEPx3 in 29, EPX4 in 10, VIPX4 in 9, and other in 18 pts. All pts had surgical resection of non-RP disease. None had RPLND. 84 pts had lung nodule resection, 16 had mediastinal LN, 8 had cervical LN, 5 had liver, 6 had bone, and 20 had brain met resection. Of the 76 pts with teratomatous elements in the orchiectomy, 41 (53.9%) had teratoma and 24 (31.6%) had non-teratoma GCT in post-chemo non-RP surgical specimens. Of the 58 pts without teratoma in the orchiectomy, 9 (15.5%) had teratoma and 34 (58.6%) had non-teratoma GCT in the non-RP surgical resection specimens. Teratoma in the orchiectomy was a predictor of non-RP teratoma (Fisher’s exact test P&lt;0.0001). Conclusions: The presence of teratoma in orchiectomy predicts teratoma in residual post-chemo non-RP disease in pts who do not undergo RPLND. The absence of teratoma in orchiectomy should not preclude resection of residual non-RP disease given a subset of patients had persistent GCT. [Table: see text]

Delivering Chemotherapy to a Metastatic Poor Risk Testicular Cancer Patient on Hemodialysis

A standard curative intent approach of chemotherapy treatment for metastatic testicular cancer has been well established. However, there is little guidance for patients undergoing hemodialysis (HD) who require chemotherapy for this disease. Thus, we describe our treatment approach and rationale for a patient on HD with poor risk metastatic nonseminomatous germ cell tumor involving the testicle, lymph nodes, liver, and bone. After orchiectomy, five cycles of cisplatin and modified dose etoposide were delivered and strategically timed with HD. Treatment was complicated by significant neuropathy. Surgical resection of two liver lesions was performed after chemotherapy. Ten years post-chemotherapy, he remains free of clinical, biochemical, or radiological recurrence. While our patient remains free of disease after this treatment, the optimal chemotherapy and dialysis dose and schedule to maximize cure and minimize toxicity remains unknown.

Viable germ cell tumor and teratoma can be distinguished from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens by a combination of microRNA-371a-3p and 375-5p.

421 Background: Our objective was to identify a combination of microRNAs (miRNA) to differentiate between viable tumor (V) or teratoma (T) and necrosis/fibrosis (N) in pcRPLND specimens of metastatic nonseminomatous germ cell tumor (NSGCT) patients with residual masses ≥1cm after chemotherapy. Our hypothesis is that a biomarker guided therapy could reduce overtreatment with pcRPLND in patients with only N. Methods: Forty-eight patients were identified, n = 16 each with T/V/N. Representative regions of T/V/N were microdissected, subsequently total RNA was isolated and miRNA expression was analyzed for miR-371a-3p, 375-3p, and 375-5p using qPCR. ROC analysis was performed for each miRNA and for all combinations in order to determine the discriminatory capacity of V and T vs. N. Results: For the group comparisons of V vs. N miR-371a-3p achieved the highest fold change (FC) of 31.1 (p = 0.023) while for T vs. N miR-375-5p performed best (FC 64,2; p &lt; 0.001). Likewise, the most accurate AUC for V was 0.75 using miR-371a-3p, for T 0.80 using miR-375-5p. Combining the best performing miRNAs for V and T resulted in an AUC of 0.94 with a sensitivity of 93.75, specificity of 93.75, PPV of 96.8 and NPV of 83.3. Conclusions: In pcRPLND tissue samples V and T could be distinguished from necrosis/fibrosis by combining miR-371a-3p and miR-375-5p with great accuracy. This combination of miRNAs might serve as new biomarker in the future, in order to spare miRNA-negative patients from pcRPLND. However, further studies analyzing patient’s serum are needed to confirm the clinical impact of these biomarkers.

Randomized phase 2 trial of maintenance oral etoposide or observation following high-dose chemotherapy for relapsed metastatic germ cell tumor.

TPS429 Background: High-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplant (PBSCT) is effective salvage therapy in patients with relapsed germ-cell tumors (GCT). Utilizing HDCT and PBSCT in the 2nd line setting, cures can be achieved in about 60% of patients with relapsed non-seminoma. Maintenance daily oral etoposide after salvage therapy has been shown effective in inducing remissions (J Clin Oncol 1995;13:1167-9). We evaluate the efficacy and safety of maintenance daily oral etoposide after HDCT+PBSCT in patients with relapsed non-seminoma. Methods: This randomized phase II open label trial is evaluating maintenance oral etoposide after HDCT+PBSCT. Eligible patients are adults with metastatic non-seminomatous GCT who have progressive disease after first-line cisplatin-based combination chemotherapy. All patients will complete initial salvage with HDCT+PBSCT with the carboplatin/etoposide Indiana protocol x2 tandem cycles. All patients should have normal or declining tumor markers (AFP and/or hCG) at time of randomization and absence of progressive disease on imaging. Adverse events from prior therapy, including hematologic toxicity, should be recovered to grade≤2 at time of randomization. Randomization should occur within ≤16 weeks from time of the 2nd cycle of HDCT. Patients with primary mediastinal non-seminoma are eligible. Patients with relapsed pure seminoma are excluded. Patients are randomized in 1:1 ratio to receive maintenance etoposide vs. standard of care surveillance post HDCT. Randomization will be stratified by platinum refractory status defined as progression within 4 weeks of first-line chemotherapy (yes vs no). Patients randomized to treatment arm will receive oral etoposide 50mg/m2 daily for 21 consecutive days of 28 day cycles. A total of 3 cycles will be delivered. Weekly labs including CBC w differential will be checked to detect hematological toxicity. The primary objective is to compare the 12-month progression-free survival (PFS) for maintenance etoposide vs observation in patients with relapsed non-seminoma post HDCT. Secondary objectives include to assess the toxicity and tolerability of maintenance etoposide, and 12-month overall survival. Exploratory analysis of the biomarker micro-RNA371 at time of randomization and correlation with disease progression/relapse will be performed. As of September 20, 2021, 5 of the total sample (N = 64) have been enrolled and randomized. Clinical trial information: NCT04804007.

The absence of spermatogenesis in radical orchiectomy specimen is associated with advanced-stage nonseminomatous testicular cancer.

To assess if clinical, pathological, and spermatogenesis factors are associated with clinical staging in patients with testicular germ cell tumors. We retrospectively reviewed the pathology reports and slides from 267 men who underwent radical orchiectomy for testicular cancer at our institution during 1998-2019. Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with advanced disease stage at diagnosis. Of 267 male patients, 115 (43%) patients had testicular non-seminomatous germ cell tumors (NSGCT) and 152 (57%) seminomatous germ cell tumors (SGCT). Among NSGCT patients, those presenting with metastatic disease had a higher proportion of predominant (>50%) embryonal carcinoma (64% vs. 43%, respectively, P = 0.03), and lymphovascular invasion (45.8% vs. 26.6%, respectively, P = 0.03) than non-metastatic patients. Spermatogenesis was observed in 56/65 (86.2%) and 36/49 (73.5%) of non-metastatic and metastatic NSGCT patients, respectively (P = 0.09). On semen analysis, severe oligospermia (<5 million/ml) was more common in metastatic than in non-metastatic NSGCT (26.5% vs. 8.3%, respectively, P = 0.04). On multivariate analysis, predominant embryonal carcinoma and lack of spermatogenesis in pathological specimens were associated with metastatic disease. The absence of spermatogenesis and a high proportion of embryonal carcinoma was associated with advanced disease in patients with NSGCT. Whether it may also translate as a predictor of oncologic outcome needs further evaluation.

31. GENETIC CONTROL OF DECONVOLVED BRAIN CELL-TYPES

Choriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.We reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.Our cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).While PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

TU17. GENOME-WIDE ANALYSIS OF PSYCHOLOGICAL RESILIENCE

Choriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.We reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.Our cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).While PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

Surveillance after complete response in patients with metastatic non-seminomatous germ-cell tumor (NSGCT).

5018 Background: The optimal management of patients (pts) with complete response (CR) after first-line chemotherapy remains unsettled with guidelines recommending either surveillance or retroperitoneal LN dissection (RPLND). We present long-term outcomes from a large dataset of pts managed with surveillance after achieving CR to first-line chemotherapy. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT treated between 1990-2017 who achieved a CR after first-line chemotherapy. CR was defined as normalization of tumor markers (AFP+hCG) and no residual mass &gt; 1cm. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Results: 388 pts met eligibility and were included in this analysis. Median age at diagnosis was 28.4 (range, 13-61.5). Primary site was testis in 385 pts (99%). Primary tumor predominant histology was embryonal ca (241), mixed (61), seminoma (31), yolk sac tumor (20), choriocarcinoma (10), and teratoma (14). 126 pts (32.5%) had teratoma in the primary tumor. Metastasis sites were retroperitoneum (295), mediastinal LN (15), pulmonary (149), liver (15), bone (7), and brain (6). IGCCCG risk was good in 325, intermediate in 25, and poor in 32 pts. Pre-chemotherapy retroperitoneal LN size was available in 232 pts: &lt; 3cm in 170 and ≥3cm in 62. Median pre-chemo AFP was 10.7 (1-31,000) and hCG was 16.5 (0-595,930). First-line chemo was BEPx3 in 274, BEPx4 in 30, other regimens in 82 pts. With a median follow-up of 3.9 yrs, 34 pts (8.8%) progressed. At most recent follow-up, 363 (93.6%) pts were alive with no evidence of disease and 10 pts (2.6%) died of their disease. The estimated 2-yr PFS was 90.1% (95% CI: 86.2-93%) and 2-yr OS was 97.8% (95% CI: 95.2-99%). The estimated 2-yr PFS by IGCCCG risk category was 90.4% for good vs 90.4% for intermediate vs 86.5% for poor risk (p = 0.23), and the estimated 2-yr OS was 98.6% for good vs 95.5% for intermediate vs 92.9% for poor risk disease respectively (p = 0.002). For the 34 pts who progressed on surveillance, 16 (4%) progressed in the retroperitoneum only. 3 pts had malignant transformation of teratoma to PNET, adenocarcinoma, or other elements. 11 of progressed pts were treated with surgery, 12 were treated with salvage chemo, and 11 were treated with surgery+chemo. At most recent follow up, 21 of progressed pts had NED, 10 had died of disease, and 3 were lost to follow up. Conclusions: Pts with metastatic NSGCT who achieve CR after first-line chemotherapy can be safely observed with surveillance. Most pts who relapse can be salvaged with surgery and/or chemotherapy.