Advanced Nonseminomatous Germ Cell Tumors Research Articles

Survival outcomes of postchemotherapy retroperitoneal lymph node dissection for nonseminomatous germ cell tumors: A retrospective cohort study from a single tertiary center in South India.

Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]-83%-97%) and the overall survival (OS) rate was 90% (95% CI-80%-95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.

Contemporary analysis of complications after retroperitoneal lymph node dissection: Data from the National Surgical Quality Improvement Program 2006-2018.

416 Background: Retroperitoneal lymph node dissection (RPLND) offers therapeutic and diagnostic value for patients with testicular cancer. Specific indications for RPLND include management of patients with stage I-II nonseminomatous germ cell tumors (NSGCT), advanced NSGCTs with post-chemotherapy masses, and seminomas with early metastatic disease. While RPLND is an invasive and complex operation, prior research suggests complication rates are relatively low and may vary based on patient characteristics and disease-related factors. We examined the incidence of complications after RPLND and aimed to determine risk factors associated with these complications. Methods: The National Surgical Quality Improvement Program (NSQIP) database from 2006-2018 was queried for RPLND in patients with testis cancer who were identified by ICD 9 and 10 codes. All reported postoperative complications were examined and categorized by type and organ system. Univariable and multivariable logistic regressions were performed to determine risk factors associated with complications. Results: 368 RPLND procedures over the 13 year interval met inclusion criteria. The overall complication rate was 23.91% (n=88). The most common complication was bleeding requiring transfusion (n=59, 16.03%). Risk factors associated with any complication included older age (OR 1.041, p=0.003), longer operative time (OR 1.007, p<0.001), and major concomitant procedure (OR 2.429, p=0.015). As shown in the table, risk factors associated with transfusion included older age (OR 1.040, p=0.019), longer operative time (OR 1.009, p<0.001), and major concomitant procedure (OR 3.296, p=0.004). Higher pre-operative hematocrit was associated with decreased risk of transfusion (OR 0.883, p<0.001). M+ (metastatic) disease and longer operative time were associated with an increased risk for wound, infectious, and respiratory complications. Conclusions: Based on our analysis, almost one in four patients undergoing RPLND experienced a complication. Bleeding requiring transfusion was the most common complication and was associated with patient age, preoperative hematocrit, operative time, and major concomitant procedure. Urologic surgeons may seek to optimize hematocrit prior to surgery, especially when major concomitant procedure may be necessary. [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.

Need for organ preservation in postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).

5031 Background: The aim ofPC-RPLND for advanced nonseminomatous germ cell tumors is to resect all remaining metastatic tissue. So far, the resection of adjacent visceral or vascular organs is also commonly performed to achieve complete resection of the residual mass. To determine the possibility of more organ preservation, we aimed to analyze the pathohistology of patients with adjunctive surgery as the frequency of metastatic involvement in those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 as a 2-center study and identified 242 (20.1%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T and N were present in 54 (22%), 94 (39%) and 94 (39%) of all patients with adjunct resected organs. In 242 patients, 325 adjunct organs were resected with 66 (27.3%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 77; V: 29% T: 39% N: 32%), followed by V. Cava (n = 67; V: 25% T: 36%, N: 39%) and partial liver resections (n = 50; V: 16%, T: 30%, N: 54%). Postoperative complications occurred in 30% of which 22% were Clavien grade III-V, showing no significant differences between V, T and N; p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p &lt; 0.001). Conclusions: This study shows tremendous need for more organ preservation as 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. Therefore, in case of doubt, we should increase intraoperative frozen section to avoid oncologically unnecessary adjunctive surgeries, especially nephrectomies and vascular resections. Additionally, serological or image-based means for a more accurate presurgical workup are required to spare patients with N from PC-RPLND in general.

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.

Survival of nonseminomatous germ cell tumors in pediatric patients and young adults - A stage group stratified analysis.

Testicular germ cell tumors, particularly nonseminomatous germ cell tumors (NSGCT), comprise the most common solid malignancy in male children and younger adults. While these patients experience excellent survival outcomes, few studies have characterized their survival by age. Thus, we aimed to characterize the relative survival of NSGCT by age, stratifying patients by stage group. Using the Surveillance Epidemiology and End Results (SEER) database, we divided patients with NSGCT into pediatric patients and adolescents (<19 years), young adults (19-30 years), and older adults (>30 years). Survival analysis, using Cox proportional hazards models and Kaplan Meier curves, described overall and cancer-specific survival (CSS) of each age category for Stage I-III NSGCT by stage group. A total of 14,786 patients met inclusion criteria and comprised the age groups <19 years (N=1,287), 19 to 30 years (N=7,729), and >30 years (N=5,770). Stage group distribution at presentation was similar between each group. Survival analysis demonstrated no differences in cancer-specific survival (CSS) among Stage I or II NSGCT. However, among Stage III tumors, multivariable models noted worse CSS in patients >30 years (HR=3.35 (95%CI: 1.45-7.73), P=0.005) and those 19-30 years (HR=2.28 (95%CI: 0.99-5.21), P=0.053) compared to pediatric and adolescent patients. Younger NSGCT patients experience excellent oncologic outcomes compared to their older counterparts. These survival differences by age group are largely driven by differential survival among Stage III neoplasms. Furthermore, our report lends additional evidence that age is an important prognostic factor in advanced NSGCT, including pediatric and adolescent patients.

790P Palliative chemotherapy in patients with advanced nonseminomatous germ cell tumors (aNSGCT)

790P Palliative chemotherapy in patients with advanced nonseminomatous germ cell tumors (aNSGCT)

Evaluation of the oncologic benefit of adjunctive surgery at time of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).

388 Background: PC-RPLND for advanced nonseminomatous germ cell tumors aims to resect all remaining metastatic tissue. The resection of adjacent visceral or vascular organs is commonly performed to achieving complete resection of the residual masses. However, the frequency of metastatic involvement of those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1181 patients who underwent PC-RPLND between 2008 and 2018 as a 2-center study and identified 235 (20%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T, N was present in 51 (21%), 91 (39%) and 93 (40%) of all patients with adjunct resected organs. In 235 patients, 316 adjunct organs were resected with 64 (27%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 74; V: 27% T: 39% N: 34%), followed by V. Cava (n = 66; V: 24% T: 36%, N: 40%) and partial liver resections (n = 48; V: 15%, T: 31%, N: 54%). Intraoperative complications occurred in 21% of patients (VT 32% vs N 17%, p = 0.021). Postoperative complications occurred in 35% of which 22% were Clavien Grad III-V showing no significant differences between VTN p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p &lt; 0.001). Conclusions: This study shows for the first time that 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. In case of doubt we propose an organ safe procedure with multiple intraoperative frozen section to avoiding oncologically unnecessary adjunctive surgeries especially nephrectomies and vascular resections. Additionally, a more accurate presurgical workup is required to spare patients with N from PC-RPLND.

Validation of the two best models to predict “benign” pathohistology in patients with advanced nonseminomatous germ cell tumors (NSGCT) undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).

389 Background: The aim of our study is to validate and evaluate the two currently best performing prediction models (Vergouwe and Leao) for final pathohistology in NSGCT patients undergoing PC-RPLND and we introduce a new radiomics approach. Methods: We performed a retrospective analysis including 496 patients who underwent a PC-RPLND between 2008 and 2018 to validate the two prediction models using published formulas and thresholds. ROC were plotted and AUC was calculated. We determined the optimal cut point and used bootstrapping (1,000 replications) to estimate its variability. For radiomics, lymph nodes of 80 patients were identified on CT images, semiautomatically segmented with 93 radiographic features (pyRadiomics package). A linear support vector machine algorithm was applied to analyze reproducible radiomics features. A continuous reduction of features analyzed was performed using Random Forest algorithms and ROC analysis. Results: In our validation cohort, the Vergouwe model had a significantly better AUC compared to Leao model (0.749 [CI 0.706-0.792] vs. 0.689 [0.642-0.736], p=0.004) to predict benign histology. At a threshold of &gt; 70% for the probability of benign disease, the Leao model would have avoided PC-RPLND in 8.6% with benign disease with an error rate of 5.6% for viable tumor. The Vergouwe model would avoid PC-RPLND in 23.4% with benign disease with an error rate of 12.7% for viable tumor/teratoma. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm on the training dataset resulted in an accuracy of 0.96 (93% sensitivity, 100% specificity, 100% PPV), on an independent validation cohort the accuracy was 0.81 (88% sensitivity, 72% specificity, 78% PPV). Conclusions: According to our data, the discriminatory accuracy of both models is not sufficient to safely select patients for surveillance strategy instead of PC-RPLND. The radiomics model is promising but needs prospective validation. Further studies including new biomarkers are needed to optimize the accuracy of potential prediction models.

A retrospective analysis of patients undergoing postchemotherapy retroperitoneal lymph node dissection and metastasectomy in advanced nonseminomatous germ cell tumors.

Introduction:Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and metastasectomy play an important role in the management of advanced-stage nonseminomatous germ cell tumors (NSGCT). We aimed to analyze preoperative parameters that could predict postoperative histology.Materials and Methods:We analyzed the data of 72 patients who underwent PC-RPLND and 14 patients who underwent metastasectomy after receiving cisplatin- or carboplatin-based chemotherapy for advanced stage NSGCT at our institute from 1994 to 2015. Clinical and pathological parameters such as the histology of orchidectomy, RPLND and metastasectomy, serum tumor markers, and the pre and post chemotherapy retroperitoneal lymph node size were recorded.Results:Seventy-two patients with a mean age of 28 years underwent PC-RPLND. Of the various variables evaluated, only percentage change in nodal size was found to be statistically significant in predicting necrosis (P = 0.004). A decrease of 75% was found to predict the necrosis with a specificity of 100%. There was 84.6% concordance between the histology of RPLND and that of metastasectomy.Conclusion:A 75% reduction in tumor size is highly predictive of absence of viable tumor or teratoma, however larger series are required to confirm these findings. RPLND histopathologies have a high concordance with metastasectomy histology and thus can be used as a guide to tailor further management.

Laparoscopic Resection of Residual Retroperitoneal Tumor Mass in Advanced Nonseminomatous Testicular Germ Cell Tumors; a Feasible and Safe Oncological Procedure

Ten-year oncological experience of the University Medical Center Groningen with conventional laparotomy (C-RRRTM) and laparoscopy (L-RRRTM) is described concerning resection of residual retroperitoneal tumor masses (RRTM) in a large series of patients with advanced nonseminomatous testicular germ cell tumors (NSTGCT). 150 consecutive patients with disseminated NSTGCT required adjunctive surgery after combination chemotherapy. L-RRRTM was scheduled in 89 and C-RRRTM in 61 patients. Median residual tumor diameter was 20 mm in the L-RRRTM versus 42 mm in the C-RRRTM group (p < 0.001). Conversion rate was 15% in the L-RRRTM group. Perioperative complications occurred in 5 patients (6%) in the L-RRRTM and 7 (12%, NS) in the C-RRRTM group. Median duration of L-RRRTM was 156 minutes vs. 221 minutes for C-RRRTM (p < 0.001). 17/89 patients in the L-RRRTM group had postoperative complications versus 18/61 patients in the C-RRRTM group (NS). Median postoperative stay in the L-RRRTM group was 2 vs. 6 days in the C-RRRTM group (p < 0.001). During a median follow-up of 79 months, 27 patients had recurrences: 8 (9%) in the L-RRRTM group and 19 (31%) in the C-RRRTM group (p < 0.001). Laparoscopic resection of RRTM for advanced NSTGCT is feasible and an oncologically safe option in appropriately selected patients.

Post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous germ cell tumors: A single-surgeon, Canadian experience.

Post-chemotherapy retroperitoneal lymph node dissection (PCRPLND) has a well-established role in the management of residual retroperitoneal masses >1 cm in patients with advanced non-seminomatous germ cell tumor (NSGCT). Herein, we report our single-surgeon surgical experience in a Canadian tertiary hospital. We identified 57 patients with NSGCT who received primary chemotherapy and PCRPLND from 2010-2016. Surgical complication rate was graded with Clavien-Dindo classification. Chi-squared testing was used in testing for differences in proportion of PCRPLND tumor histology vs. the historical cohorts. Chi-squared testing was also used to analyze the association between primary orchiectomy tumor histology and post-chemotherapy residual mass (PCRM) tumor histology. The overall complication rate was 23% (n=13), of which four were Clavien-Dindo grade IIIb and one was grade IVa. Fourteen percent of patients required additional procedure for resection of adjacent organs intraoperatively. There was a statistically significant difference in the distribution of PCRPLND tumor histologies (Chi-squared p=0.0187), with a lower rate of viable tumor (7%) and higher rate of teratoma (63%) compared to historical cohorts. The absence of teratoma in the primary orchiectomy specimen was associated with the findings of fibrotic/necrotic tissue in the PCRM (Chi-squared p=0.0005). Our series demonstrated that the rate of viable tumor in PCRM appears lower than published historical series, and this possibly reflects the improvement in chemotherapy delivery in a contemporary series. The high rate of teratoma in the PCRM calls for ongoing need for PCRPLND. Grade III and IV surgical complications are considered rare in our series.

903O - Redefining the IGCCCG classification in advanced non-seminoma

BackgroundThe International Germ Cell Cancer Collaborative Group (IGCCCG) has been the reference classification for assessing prognosis in men with advanced non-seminomatous germ-cell tumors (NSGCT) for more than 20 years and it relied on 5202 cases treated between 1975 and 1990. MethodsAn international consortium (30 centers/groups) contributed data on 9530 advanced NSGCT patients treated with cisplatin/etoposide based first line chemotherapy between 1990 and 2013 in prospective cohorts or clinical trials. Updated 5-year progression-free (PFS) and overall survival (OS) rates were calculated. A subset of 4874 patients with complete information on components of IGCCCG, age and lung metastases were split into training (3536) and validation sets (1338). Prognostic factors for PFS were identified in the training set (alpha=0.05) by Cox model, including (transformed) continuous factors and interactions. ResultsCompared to the 1997 IGCCCG figures, the contemporary 5-year PFS was unchanged for good and intermediate, but significantly improved for poor risk patients; whereas 5-year OS was substantially better for all risk groups (Table). The subgroup with complete data was unbiased. Besides traditional IGCCCG components, we identified older age and lung metastases as negative determinants of PFS. A nomogram including AFP, HCG (both continuous), LDH>2.5xnormal, mediastinal primary, non-pulmonary visceral metastases, age (linear) and lung metastases, with several interactions was built. Its c-index was 0.745 in the training set compared to 0.701 for the 1997 IGCCCG.Table903OTable5-year PFS IGCCCG 19975-year PFS contemporary5-year OS IGCCCG 19975-year OS contemporaryGood89 (87 – 91%)90 (89 - 91%)91 (89 - 93%)96 (95 - 97%)Intermediate75 (71 – 79%)78 (76 - 80%)79 (75 - 83%)89 (88 - 91%)Poor41 (35 – 47%)54 (52 - 56%)48 (42 - 54%)67 (65 - 69%) ConclusionsIn this modern series, PFS improved for poor risk patients, while OS improved in all IGCCCG risk groups. A new prognostic model including older age and presence of lung metastases as additional negative factors is proposed. Independent validation and comparison to the IGCCCG 1997 are being conducted and will tell if the model can identify patient subgroups who may require intensified treatment. Legal entity responsible for the studyThe International Germ Cell Cancer Collaborative Group (IGCCCG). FundingSwiss Cancer Foundation. DisclosureS. Gillessen: Advisory / Consultancy: AAA International, Active Biotech, Amgen, Astellas Pharma, Bayer, Bristol-Myers Squibb, CellSearch, Clovis, CureVac, Dendreon, ESSA Pharmaceuticals, Ferring, Innocrin Pharmaceuticals, Janssen Cilag, MaxiVAX SA, Millennium, Nectar, Novartis, Orion, Pfizer,; Licensing / Royalties: Co-inventor on patent application (WO 2009138392 A1) for a method for biomarker discover (granted in China, Europe, Japan and the US). R. de Wit: Honoraria (self): Merck, Sanofi, Bayer, Janssen, Roche and Clovis. R.A. Huddart: Honoraria (self): Janssen; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Research grant / Funding (self): CRUK; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar. All other authors have declared no conflicts of interest.

982P - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumours (NSGCT): Final results of phase II trial

BackgroundThree-weekly BEP has been a standard of CT of advanced NSGCT for last two decades. We performed a phase II study to assess the efficacy and toxicity of two-weekly aBEP regimen in the first line treatment of NSGCT. Here we report final efficacy and safety results. MethodsCT-naïve NSGCT pts with intermediate or poor prognosis (IGCCCG) received aBEP as follows: cisplatin 20mg/m2 days 1-5, etoposide 100mg/m2 days 1-5, bleomycin 30IU days 1,3,5 with G-CSF support 300mcg days 6-10. Four cycles of aBEP were administered every 2 weeks. The primary endpoint was the progression free rate. ResultsFrom 2010 to 2014, 67 pts were treated. Intermediate and poor prognosis according IGCCCG had 35 (59%) and 32 (41%) of pts, respectively. In poor prognostic group mediastinal primary tumor had 11 (34%) pts, nonpulmonary visceral metastases - 16 (50%) pts. All pts were assessed for toxicity, which included (grade 3/4, per patient) neutropenia 72%, febrile neutropenia 26%, thrombocytopenia 18%, non-neutropenic infection 3%, anemia 31%. There were no toxic deaths. Dose reduction of cisplatin, etoposide and bleomycin were done on 16 (6.4%), 22 (8.9%) and 19 (7.7%) of 247 cycles, respectively. Median number of cycles was 4 (3-5). Two pts could not receive 4-th cycle due to toxicity. Median duration of treatment (from the first to the last doses of CT) was 7.4 (6.7-10.4) weeks. Totally 44 (72%) pts were able to start 4-th cycle of aBEP by day 50 (<1 week of delay). Median time of f.-up was 74 (5-108) months. Five-years PFS and OS were 88% and 85% (intermediate risk), 63% and 53% (poor risk). There were a trend to improvement of OS in poor risk group over 3-weekly BEP regimen in our center (n=79, 5-y OS 45%, p=0.09). ConclusionsTwo-weekly BEP regimen can be safely administered to NSGCT pts with intermediate and poor prognosis. Promising efficacy of aBEP warrants confirmation in ongoing randomized trial. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Analysis of three models to predict pathohistology in patients undergoing postchemotherapy RPLND for (pcRPLND) advanced nonseminomatous germ cell tumors (NSGCT).

e16053 Background: We aim to validate the two best performing prediction models (Vergouwe and Leao) for final pathohistology in NSGCT patients undergoing pcRPLND and we introduce a new radiomics approach. Methods: A cohort of 496 patients treated between 2008 and 2018 was used to validate the 2 prediction modelsusing published formulas and thresholds.For group comparisons, we used t-test or chi-square test. ROC were plotted (sensitivity against 1-specificity) and AUC was calculated. We determined the optimal cut point and used bootstrapping (1,000 replications) to estimate its variability. A p-value of &lt; 0.05 was considered statistically significant. For radiomics, lymph nodes identified on CT images, were semiautomatically segmented with 93 radiographic features (pyRadiomics package). A linear support vector machine algorithm was applied to analyze reproducible radiomics features. A continuous reduction of features analyzed was performed using Random Forest algorithms and ROC analysis. Results: The Vergouwe model had a significantly better AUC compared to Leao model (0.749 [CI 0.706-0.792] vs. 0.689 [0.642-0.736], p = 0.004) to predict benign histology. At a threshold of &gt; 70% for the probability of benign disease, the Leao model would have avoided RLND in 8.6% with benign disease with an error rate of 5.6% for viable tumor. The Vergouwe model would avoid pcRPLND in 23.4% with benign disease with an error rate of 12.7% for viable tumor/teratoma. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm resulted in a AUC of 82% with a diagnostic sensitivity of 81% and a specificity of 83%. Conclusions: The discriminatory accuracy of both models is not sufficient to safely select patients for surveillance strategy instead of pcRPLND. The radiomics model is promising but needs prospective validation. Further studies including new biomarkers are needed to optimize the accuracy of potential prediction models.

Diagnosis and management of the growing teratoma syndrome: A single-center experience and review of the literature

ObjectivesTo evaluate the diagnostic, surgical as well as oncological outcome of patients with a growing teratoma syndrome. Material and methodsWe performed a retrospective analysis including 680 patients with advanced nonseminomatous germ cell tumors who underwent a postchemotherapy retroperitoneal lymph node dissection. The peri- and postoperative outcome of 22 patients (3%) that fulfilled the criteria of a growing teratoma syndrome were analyzed: nonseminomatous germ cell tumors with increasing tumor size during or after chemotherapy despite normalized or decreasing tumor markers. ResultsThe median tumor diameter at time of surgery was 6 cm (4–12.2). For a complete resection of the residual masses, adjunctive surgery had to be performed in 4 (18%) patients: resection of the abdominal aorta, inferior vena cava or renal vein with graft replacement, nephrectomy and resection of parts of the intestine. Eight postoperative complications occurred in 5 (23%) patients, with 4/8 of these complications affecting only one patient. Fifty percent of all complications were classified as Clavien-Dindo grade III or IV. After a median follow-up of 25 months, relapse occurred in 2 patients (9%); all but one patient is alive resulting in an overall survival of 95.5%. ConclusionsThe growing teratoma syndrome is a rare phenomenon among patients with advanced nonseminomatous germ cell tumors and necessitates complete surgical resection of the masses with curative intention. Due to its complexity and potential adjunctive surgery, the treatment should be performed in tertiary referral centers only.

Practice Patterns and Impact of Postchemotherapy Retroperitoneal Lymph Node Dissection on Testicular Cancer Outcomes

BackgroundOwing to surgical complexity and controversy regarding indications, there are wide practice variations in the use of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). ObjectiveTo evaluate patterns of PC-RPLND use in the USA and evaluate the association between PC-RPLND and survival in advanced nonseminomatous germ cell tumors (NSGCTs). Design, setting, and participantsA retrospective, observational study using National Cancer Data Base (NCDB) data from 2004–2014 for 5062 men diagnosed with stage II/III NSGCT. Outcome measurements and statistical analysisIn a comparative analysis based on receipt of PC-RPLND, the primary outcome of interest was factors associated with omission of PC-RPLND as explored via logistic regression. As a secondary outcome, we evaluated the association between PC-RPLND and overall survival (OS) via multivariable Cox regression and propensity score matching (PSM). Results and limitationsPatients undergoing PC-RPLND were more likely to be younger, white, privately insured, and reside in more educated/wealthier regions (p<0.001). Insurance status was independently associated with receipt of PC-RPLND; compared to patients with private insurance, those without insurance were significantly less likely to receive PC-RPLND (odds ratio 0.49; p<0.001). After multivariate adjustment, age, comorbidity, non-private insurance, distance from hospital, clinical stage, and risk group were independently associated with all-cause mortality. In addition, omission of PC-RPLND remained associated with all-cause mortality (hazard ratio 1.98; p<0.001). After PSM, the 5-yr OS was significantly lower among those not undergoing PC-RPLND (72% vs 77%; p=0.007). ConclusionsPC-RPLND represents a critical part of the multidisciplinary management of NSGCT. Patients with non-private insurance are less likely to undergo PC-RPLND, and omission of PC-RPLND is associated with lower OS. Patient summaryWe evaluated the practice patterns for advanced testicular cancer management and found that patients who did not undergo a postchemotherapy retroperitoneal lymph node dissection were more likely to have worse survival outcomes. Patients with unfavorable insurance were less likely to receive this surgical treatment.

Histologic and Oncologic Outcomes Following Liver Mass Resection With Retroperitoneal Lymph Node Dissection in Patients With Nonseminomatous Germ Cell Tumor

To evaluate the oncologic outcomes and histologic concordance of postchemotherapy residual liver mass resection with postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Retrospective review of our prospectively maintained germ cell tumor (GCT) surgical database identified patients with nonseminomatous GCT who underwent both postchemotherapy residual liver mass resection and PC-RPLND between 1990 and 2015. A total of 36 patients were identified, of whom 29 (81%) presented with a liver mass at initial diagnosis and 17 (47%) received second-line chemotherapy before liver resection. Teratoma was found in 8 (22%) and 5 (14%) of PC-RPLND and liver resection specimens, respectively. Viable GCT was found in 5 (14%) and 4 (11%) of PC-RPLND and liver resection specimens, respectively. Histologic discordance was observed in 4 of 19 patients (21%; 95% confidence interval [CI] 6.1%-46%); in all cases, liver resection specimens contained teratoma or viable GCT while PC-RPLND revealed only fibrosis or necrosis. At 3 years after surgical intervention, the Kaplan-Meier estimated probability of cancer-specific survival was 75% (95% CI 55%-85%) and the probability of progression-free survival was 75% (95% CI 56%-87%). In this contemporary cohort, clinically significant discordance was observed between the histology of metastatic liver masses and that of retroperitoneal lymph nodes. The benefit of postchemotherapy liver mass resection for patients with advanced nonseminomatous GCT is supported by favorable survival outcomes. Until more reliable predictors of postchemotherapy histology exist, complete surgical resection of all sites of residual disease should be performed whenever feasible.

MP37-20 SURGICAL MANAGEMENT OF THE GROWING TERATOMA SYNDROME: A MULTICENTER STUDY

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I1 Apr 2018MP37-20 SURGICAL MANAGEMENT OF THE GROWING TERATOMA SYNDROME: A MULTICENTER STUDY Pia Paffenholz, David Pfister, and Axel Heidenreich Pia PaffenholzPia Paffenholz More articles by this author , David PfisterDavid Pfister More articles by this author , and Axel HeidenreichAxel Heidenreich More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1226AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The growing teratoma syndrome (GTS) is an infrequent clinical phenomenon constituting only about 2 to 8% of all testis cancer patients. Data in the literature on the therapy of GTS are sparse, reflecting the rarity of the disease. The purpose of this study was to evaluate the diagnostic, surgical and oncological outcome of patients with GTS treated in the 21st century. METHODS We performed a retrospective analysis including 680 patients with advanced non-seminomatous germ cell tumors that underwent a post-chemotherapeutic retroperitoneal lymph node dissection. We analysed the peri- and postoperative outcome of 22 patients (3%) that fulfilled the criteria of a GTS: enlarging metastatic mass in the retroperitoneum or visceral organs during systemic chemotherapy with normalized or decreasing tumor markers. RESULTS Mean patient age was 28 years (22-34). 17 (81%) and 3 (14%) patients were classified as good or intermediate prognosis according to the IGCCCG risk classification, while 1 patient (5%) was in the poor prognosis group. The median tumour diameter at time of surgery was 6 cm (4-12.2). In order to completely resect the residual masses, adjunctive surgery had to be performed in 4 (18%) of all patients: resection of the abdominal aorta, inferior vena cava or renal vain with a graft replacement, nephrectomy and resection of parts of the intestine. 8 postoperative minor or major complications occurred, with 4 complications affecting only 1 patient. After a median follow-up of 25 month (8-47), 2 (9%) patients developed an in-field or out-field recurrence, respectively; all but one patients are alive showing an overall survival of 95.5%. CONCLUSIONS GTS is a rare disease among patients with advanced non-seminomatous germ cell tumors and necessitates complete surgical resection of the masses with curative intention. Due to its complexity, surgery should be performed in tertiary referral centers only. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e499 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Pia Paffenholz More articles by this author David Pfister More articles by this author Axel Heidenreich More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

914P - Do patients (pts) with advanced nonseminomatous germ cell tumors (aNSGCT) and unfavorable time to normalization (TTN) of tumor markers benefit with prolongation of 1-st line chemotherapy (ChT)?

914P - Do patients (pts) with advanced nonseminomatous germ cell tumors (aNSGCT) and unfavorable time to normalization (TTN) of tumor markers benefit with prolongation of 1-st line chemotherapy (ChT)?