Metastatic Testicular Nonseminomatous Germ Cell Research Articles

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.

Prediction models for the viability of pulmonary metastatic lesions after chemotherapy in nonseminomatous germ cell tumors.

To analyze predictors associated with viable cells in pulmonary residual lesions after chemotherapy for metastatic testicular nonseminomatous germ cell tumors and to develop models to prioritize pulmonary resection. Between 2008 and 2017, 40 patients underwent pulmonary metastasectomy after chemotherapy for nonseminomatous germ cell tumors. We evaluated these patients, and 326 pulmonary residual lesions were confirmed using computed tomography and pathological evaluations. Relationships with outcomes were analyzed using logistic regression analyses. Risk prediction models were developed, and predictive probabilities for the risk of viable cells were estimated. Histological examinations showed that 73 (22%) pulmonary residual lesions contained viable cells: teratomas, 46 (14%); and cancer cells, 37 (11%). Multivariate analyses showed that the predictors associated with cancer cells in the residual lesions were elevated tumor marker levels, multiregimen chemotherapy, increased tumor size 6months before surgery and the histological composition of the primary lesion, including yolk sac tumors. Additional predictors associated with teratomas were aspect ratio and histological composition of the primary lesion, including teratomas. Intratumoral heterogeneity contributes to nonseminomatous germ cell tumor chemoresistance, and primary lesion site yolk sac tumors and teratomas are associated with greater risks of viable cells. Increased residual lesion size during chemotherapy could also be a predictor. Our simple model can predict the presence of viable cells in residual lesions after chemotherapy, and it might assist in decision-making and prioritizing pulmonary residual lesion resection.

Radiomics allows for detection of benign and malignant histopathology in patients with metastatic testicular germ cell tumors prior to post-chemotherapy retroperitoneal lymph node dissection.

To evaluate whether a computed tomography (CT) radiomics-based machine learning classifier can predict histopathology of lymph nodes (LNs) after post-chemotherapy LN dissection (pcRPLND) in patients with metastatic non-seminomatous testicular germ cell tumors (NSTGCTs). Eighty patients with retroperitoneal LN metastases and contrast-enhanced CT were included into this retrospective study. Resected LNs were histopathologically classified into "benign" (necrosis/fibrosis) or "malignant" (viable tumor/teratoma). On CT imaging, 204 corresponding LNs were segmented and 97 radiomic features per LN were extracted after standardized image processing. The dataset was split into training, test, and validation sets. After stepwise feature reduction based on reproducibility, variable importance, and correlation analyses, a gradient-boosted tree was trained and tuned on the selected most important features using the training and test datasets. Model validation was performed on the independent validation dataset. The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a misclassification of 8 of 36 benign LNs as malignant and 4 of 25 malignant LNs as benign (sensitivity 88%, specificity 72%, negative predictive value 88%). In contrast, a model containing only the LN volume resulted in a classification accuracy of 0.68 with 64% sensitivity and 68% specificity. CT radiomics represents an exciting new tool for improved prediction of the presence of malignant histopathology in retroperitoneal LN metastases from NSTGCTs, aiming at reducing overtreatment in this group of young patients. Thus, the presented approach should be combined with established clinical biomarkers and further validated in larger, prospective clinical trials. • Patients with metastatic non-seminomatous testicular germ cell tumors undergoing post-chemotherapy retroperitoneal lymph node dissection of residual lesions show overtreatment in up to 50%. • We assessed whether a CT radiomics-based machine learning classifier can predict histopathology of lymph nodes after post-chemotherapy lymph node dissection. • The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a sensitivity of 88% and a specificity of 78%, thus allowing for prediction of the presence of viable tumor or teratoma in retroperitoneal lymph node metastases.

CXCL12 expression is an adverse predictor for disease recurrence in patients with metastatic non-seminomatous testicular germ cell tumors

BackgroundTo validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT).MethodsCXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests.ResultsCXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease.ConclusionsCXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.

Prognostic factors of metastatic testicular non-seminomatous germ cell tumors after chemotherapy

BackgroundWe evaluated the prognostic factors of metastatic testicular non-seminomatous germ cell tumor (NSGCT) after chemotherapy. Materials and methodsData from 20 metastatic testicular NSGCT patients were retrospectively collected between January 2002 and December 2015. The evaluation of prognostic factors included age, pulmonary metastasis, cancer stage, International Germ Cell Cancer Collaborative Group (IGCCCG) classification, and histology. ResultsTwelve (60%) and eight (40%) patients had stage 2 and 3 disease, respectively. Good, intermediate, and poor prognoses were ten, six, and four patients, respectively. Eight patients (40%) were aged above 30 years at detection of testicular; cancer, and seven patients (35%) had pulmonary metastases. Sixteen patients had mixed germ cell tumors (MGCTs) only, Four were unfavorable histology (two MGCTs with choriocarcinoma-predominant, one pure choriocarcinoma and MGCTs with embryonal rhabdomyosarcoma transformation). Thirteen patients (65%) showed no evidence of disease (NED), and 7 patients (35%) that did not survive post therapy. Pulmonary metastases (P = 0.02), unfavorable histology (P = 0.007) were found to be prognostic factors of NED in patients with metastatic testicular NSGCTs. Age (P = 0.06) and stage (P = 0.06) showed considerable trend of significance. But risk group of IGCCCG exhibited no significant difference (P = 1). ConclusionThe presence of pulmonary metastases, and unfavorable histology but not GCCCG classification were associated with poor prognosis in in patients with metastatic testicular NSGCTs. Prognostic reclassification for IGCCCG groups is suggested from our study.

Distinguishing fibrosis/necrosis from teratoma or viable disease in the retroperitoneum in post-chemotherapy, nonseminomatous testicular germ cell tumor using quantitative CT texture analysis.

563 Background: In metastatic nonseminomatous testicular germ cell tumor (NSGCT), post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is indicated for residual masses > 1 cm because of these 45% will be fibrosis/necrosis, 45% will be teratoma and 15% will be viable malignancy. There is no imaging test that reliably distinguishes lymph nodes (LNs) with tumor (teratoma or malignancy) from LNs with fibrosis/necrosis. We evaluated whether quantitative CT texture analysis (TA) could make this differentiation. Methods: Pre- and post-chemotherapy CTs (all same phase and slice thickness) were reviewed in 22 NSGCT patients with RP LNs > 1 cm post chemotherapy. After manual segmentation of RP LNs on a 3D workstation, 187 TA metrics were derived, using 2D/3D gray-level co-occurrence matrix (GLCM), 2D/3D gray-level difference matrix (GLDM), and spectral analysis. Metrics were derived 2 ways: from post-chemotherapy CTs alone, and also as a difference between pre- and post-chemotherapy CTs, resulting in 374 metrics. PC-RPLND pathology was correlated with CT data at 88 LN stations in these 22 patients. Results: 15 imaging metrics showed a significant difference (p ≤ 0.05) between LN stations with only fibrosis/necrosis and those with teratoma or viable tumor. Seven were derived from the difference between pre- and post-chemotherapy CTs: 4 using a 2D GLCM (coronal standard deviation, coronal square root of variance, coronal mean, and coronal sum of average), and 3 using a 2D GLDM (axial variance, axial square root of variance, and coronal variance). The other 8 were derived from post-chemotherapy CTs alone: 7 using a 2D GLCM (sagittal square root of variance, sagittal standard deviation, coronal square root of variance, coronal mean, coronal standard deviation, coronal sum of average, and coronal entropy) and 1 using a 2D GLDM (sagittal sum entropy). Conclusions: CT TA shows promise in differentiating necrosis from teratoma or viable tumor in RP LNs in post-chemotherapy NSGCT. A larger study is needed to further test this method, towards a long-term goal of potentially allowing some patients to avoid PC-RPLND.

Clinical outcome of postchemotherapy retroperitoneal lymph node dissection and predicting retroperitoneal histology in advanced nonseminomatous germ cell tumours of the testis

Objective: To explore the clinical outcome of advanced testicular nonseminomatous germ cell cancer patients undergoing post chemotherapy retroperitoneal lymph node dissection (PC-RPLND), and to analyze the relevant prognostic factors of lymph node pathological. Methods: A total of 43 consecutive testicular nonseminomatous germ cell cancer patients underwent PC-RPLND between March 2001 and December 2014 in Department of Urology at Sun Yat-sen University Cancer Center were retrospectively reviewed. The average age of the patients was (29.0±11.5) years (ranging from 12 to 58 years). Before PC-RPLND, 22 patients were classified as phase Ⅱ, while 21 were phase Ⅲ. Primary tumor histology revealed seminomatous elements in 19 cases, embryonal cell carcinoma in 22 cases, yolk sac tumor in 13 cases, chorionic carcinoma in 3 cases, mature teratomatous elements in 11 and immature teratomatous elements in 2 cases. Patients were treated with cisplatin-based chemotherapy after orchectomy and then underwent surgical resection of retroperitoneal lymph nodes.After PC-RPLND, all patients underwent a periodic review including the blood routine, biochemistry routine and computed tomography or ultrasonograph of the chest, the abdomen and the pelvis. The association of pathological data with patient's clinic features and the correlations between molecular features detected with each other were assessed by the t test, χ(2) and Fisher's exact test. Multivariate logistic regression were used to assess prognostic factors. Results: The median operative time was 278 minutes (ranging from 50 to 715 minutes). Median blood loss was 425 ml (ranging from 50 to 5 000 ml). Eight patients received blood transfusion intra-operatively, 2 patients underwent adjunctive surgical procedures, 4 patients developed ileus and 4 had an ascites chylosus following PC-RPLND, 1 patient had a postoperative hyperthermia and retrograde ejaculation was present in 10 patients. The transverse diameter of the residual tumor in patients ranged from 0.8 to 18.2 cm. Necrosis, teratoma and viable germ cell tumors were found in 15, 17 and 11 of all patients. The median follow-up time was 46 months (ranging from 6 to 169 months). There were 39 patients had no tumor recurrence, 7 patients were found recurrence after PC-RPLND, 5 died of malignant germ cell tumor. The normal serum lactate dehydrogenase (LDH) level before chemotherapy (HR=25.811, 95%CI: 0.678 to 982.624, P=0.017) and relative changes more than 50% in retroperitoneal lymph node size (HR=0.016, 95%CI: 0 to 0.698, P=0.032) were statistically significant prognostic factors of the presence of necrosis. Conclusions: Since most residual masses are not sensitive to chemotherapy, PC-RPLND is still an essential part of the treatment of metastatic testicular nonseminomatous germ cell cancer. Patients with the normal serum LDH level before chemotherapy and a shrinkage of 50% or more in retroperitoneal mass have a considerably chance of having necrosis in the retroperitoneum resection. This may help to refine the selection of candidates for PC-RPLND.

Therapeutic Potential of SOX2 Inhibition for Embryonal Carcinoma

Some nonseminomatous germ cell tumors are resistant to any type of chemotherapy. Control of embryonal carcinoma cells is crucial to manage nonseminomatous germ cell tumors. We established SOX2 targeting therapy in an embryonal carcinoma model. SOX2 expression was evaluated in a series of testicular germ cell tumor tissue samples. The antitumor effect of SOX2 knockdown was analyzed in vitro and in vivo using an embryonal carcinoma model. In testicular germ cell tumor tissue SOX2 was expressed in the foci of embryonal carcinoma but negative in seminoma and yolk sac tumors. In an embryonal carcinoma model SOX2-siRNA induced apoptotic cell death in vitro and significant growth suppression in vivo. This study shows the therapeutic potential of SOX2 silencing for embryonal carcinoma. However, further improvements are needed in SOX2-siRNA delivery to the tumor.

Commentary on “Survival after resection for metastatic testicular nonseminomatous germ cell cancer to the lung or mediastinum.” Kenneth A. Kesler, a Laura E. Kruter, a Susan M. Perkins, b Karen M. Rieger, a Katherine J. Sullivan, a Matthew L. Runyan, a John W. Brown, a Lawrence H. Einhorn, caDepartment of Surgery, Cardiothoracic Division and Medicine, Indiana University Melvin and Bren

Commentary on “Survival after resection for metastatic testicular nonseminomatous germ cell cancer to the lung or mediastinum.” Kenneth A. Kesler, a Laura E. Kruter, a Susan M. Perkins, b Karen M. Rieger, a Katherine J. Sullivan, a Matthew L. Runyan, a John W. Brown, a Lawrence H. Einhorn, caDepartment of Surgery, Cardiothoracic Division and Medicine, Indiana University Melvin and Bren

Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors

BackgroundResection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT).MethodsAt the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with cisplatin combination chemotherapy between 2005 and 2007. Laparoscopic RRRTM was performed for patients with RRTM located less than 5 cm ventrally or laterally from the aorta or the vena cava. The 29 patients who fulfilled the criteria had a median age of 25 years (range, 16–59 years). The stages of disease before chemotherapy treatment according to the Royal Marsden classification were 2A (n = 6, 21%), 2B (n = 14, 48%), 2C (n = 3, 10%), and 4 with a lymph node status of N2 (n = 6, 21%).ResultsThe median duration of laparoscopy was 198 min (range, 122–325 min). The median diameter of the RRTM was 21 mm (range, 11–47 mm). Laparoscopic resection was successful for 25 patients (86%). Conversion was necessary for three patients (10%): two due to bleeding and one because of obesity. One nonplanned hand-assisted procedure (3%) also had to be performed. Histologic examination of the specimens showed fibrosis or necrosis in 12 patients (41%), mature teratoma in 16 patients (55%), and viable tumor in 1 patient (3%). The median hospital stay was 1 day (range, 1–6 days). During a median follow-up period of 47 months (29–70 months), one patient experienced an early relapse (1 month after the end of treatment) (4%).ConclusionFor properly selected patients, laparoscopic resection of RRTM is an improvement in the combined treatment of disseminated NSTGCT and associated with a short hospital stay, minimal morbidity, rapid recovery, and a neat cosmetic result. Long-term data to prove oncologic efficacy are awaited.

Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor: A Report From the Swedish-Norwegian Testicular Cancer Group

From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for β-human chorionic gonadotropin (β-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.

Clinical outcome following post‐chemotherapy retroperitoneal lymph node dissection in men with intermediate‐ and poor‐risk nonseminomatous germ cell tumour

To evaluate the outcome in patients treated with chemotherapy and retroperitoneal lymph node dissection (RPLND) after an initial diagnosis of International Germ Cell Cancer Collaborative Group (IGCCCG) intermediate- and poor-risk metastatic nonseminomatous testicular germ cell tumour (NSGCT), as the integration of chemotherapy and surgery in managing advanced NSGCT continues to develop. Between 1989 and 2003, 157 patients initially diagnosed with IGCCCG intermediate- and poor-risk NSGCT had RPLND after chemotherapy at the authors' institution, with a median follow-up of 36 months. Progression-free probability (PFP) and disease-specific survival (DSS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to assess the prognostic significance of risk factors for disease progression after RPLND. In all, 68 (43%) and 89 (57%) patients were assigned as intermediate- and poor-risk, respectively. At the time of RPLND the median residual retroperitoneal mass was 3.0 cm and 29 (19%) men had elevated serum tumour markers (alpha-fetoprotein, human chorionic gonadotrophin, or both). Retroperitoneal residual masses were completely resected in 147 (94%) patients; retroperitoneal histology revealed fibrosis in 73 (47%), teratoma in 63 (40%) and viable GCT in 21 (13%). The 5-year overall DSS and PFP were 81% and 70%, respectively. Patients with poor-risk NSGCT were at no greater risk of disease progression than those with intermediate-risk NSGCT. In a multivariate analysis, residual mass size, incomplete surgical resection and the presence of teratoma and viable germ cell cancer independently predicted disease progression after RPLND. Patients with advanced NSGCT have long-term freedom from disease progression when chemotherapy is combined with resection of residual masses. Our data suggest that the tumour response to chemotherapy, coupled with complete resection of all residual masses, predicts long-term freedom from disease progression.

Late relapse of metastatic testicular nonseminomatous germ cell cancer: surgery is needed for cure: Geldart TR, Gale J, McKendrick J, Kirby J, Mead G, Medical Oncology Unit, Southhampton University Hospitals NHS Trust, Southhampton, United Kingdom

To identify patients with late relapse of metastatic, nonseminomatous germ cell tumour (NSGCT) and to evaluate the patterns of relapse, treatment and outcome, as such relapse at >2 years after complete remission to treatment for metastatic disease (late relapse) is uncommon, but with prolonged follow-up is becoming increasingly recognized. Between 1980 and 2004, 1405 patients with testicular GCTs were identified who presented to Southampton University Hospital; 742 had NSGCTs or combined testicular GCTs, of whom 405 received primary chemotherapy for metastatic disease. In all, 329 (81%) patients achieved a complete response (CR) to initial treatment, with 101 of them (31%) requiring surgical resection of residual masses after chemotherapy. Any patient relapsing at >2 years after a CR to initial treatment (late relapse) was assessed in detail. In all, 20 patients had a late relapse, 17 of whom received initial treatment locally and three of whom were initially treated elsewhere. Most (65%) late relapses were asymptomatic and detected by routine cross-sectional imaging or rising levels of tumour markers. Late relapse occurred at a median (range) of 108 (26–217) months (approximately 9 years) after CR. Fifteen (75%) patients underwent only surgery for late relapse, including five who had invasive malignant germ cell cancer within the resected specimens. Fourteen of 15 surgically treated patients remained alive at a median of 44 (9–184) months from initial treatment for late relapse; one had died with progressive recurrent germ cell/epithelial malignancy. Five (25%) patients were initially treated with chemotherapy for late relapse; three of them died from progressive germ cell cancer and the two survivors both had surgical excision of residual abnormalities after salvage chemotherapy. Overall, 15 of 20 (75%) men remain alive with no evidence of disease; one further patient is currently undergoing salvage treatment for his third relapse. Late relapse is uncommon after modern therapy for metastatic GCTs. Surgical treatment for localized disease, where possible, is associated with prolonged disease-free and overall survival. By contrast, chemotherapy is associated with a low response rate and a poor outcome.

Late relapse of metastatic testicular nonseminomatous germ cell cancer: surgery is needed for cure

To identify patients with late relapse of metastatic, nonseminomatous germ cell tumour (NSGCT) and to evaluate the patterns of relapse, treatment and outcome, as such relapse at >2 years after complete remission to treatment for metastatic disease (late relapse) is uncommon, but with prolonged follow-up is becoming increasingly recognized. Between 1980 and 2004, 1405 patients with testicular GCTs were identified who presented to Southampton University Hospital; 742 had NSGCTs or combined testicular GCTs, of whom 405 received primary chemotherapy for metastatic disease. In all, 329 (81%) patients achieved a complete response (CR) to initial treatment, with 101 of them (31%) requiring surgical resection of residual masses after chemotherapy. Any patient relapsing at >2 years after a CR to initial treatment (late relapse) was assessed in detail. In all, 20 patients had a late relapse, 17 of whom received initial treatment locally and three of whom were initially treated elsewhere. Most (65%) late relapses were asymptomatic and detected by routine cross-sectional imaging or rising levels of tumour markers. Late relapse occurred at a median (range) of 108 (26-217) months (approximately 9 years) after CR. Fifteen (75%) patients underwent only surgery for late relapse, including five who had invasive malignant germ cell cancer within the resected specimens. Fourteen of 15 surgically treated patients remained alive at a median of 44 (9-184) months from initial treatment for late relapse; one had died with progressive recurrent germ cell/epithelial malignancy. Five (25%) patients were initially treated with chemotherapy for late relapse; three of them died from progressive germ cell cancer and the two survivors both had surgical excision of residual abnormalities after salvage chemotherapy. Overall, 15 of 20 (75%) men remain alive with no evidence of disease; one further patient is currently undergoing salvage treatment for his third relapse. Late relapse is uncommon after modern therapy for metastatic GCTs. Surgical treatment for localized disease, where possible, is associated with prolonged disease-free and overall survival. By contrast, chemotherapy is associated with a low response rate and a poor outcome.

Postchemotherapy resections of residual masses from metastatic nonseminomatous testicular germ cell tumors. A Spanish Germ Cell Group study

4525 Background: After chemotherapy for metastatic testicular tumors masses may remain. We analyze factors influencing histology and long-term evolution of patients with post-chemotherapy residual masses. Methods: 352 patients with nonseminomatous germ cell tumors with postchemotherapy residual masses and negative tumor markers were selected from the database of the Spanish Germ Cell Group between December 94 and February 04. Our protocol recommends surgical resection of masses larger than 2 cm. Patients with masses between 1 and 2 cm were offered follow-up or surgical resection. Of them 292 were finally operated: IGCCCG class: 137 (47%), 72 and 83 (28%) for good, intermediate and bad prognosis group respectively. Results: Median follow-up: 4 yrs. Thirty patients need 2 resections, 8 patients 3 and 3 patients 4 surgical maneuvers. Histology of masses: necrosis in 116 (40%), teratoma in 135 (46%), malignant tumor in 41 (14%). IGCCCG and Royal Marsdem class, histology of the primary, age and prechemotherapy size were correlated (X2 test) with histology of the residual masses. Lesions >5 cm before chemo and intermediate or bad prognosis group of the IGCCCG significantly correlated with necrosis. Statistically significant factors predicting teratoma were primary containing teratomatous elements, patient belonging to the good prognosis group and lesions below 5 cm before treatment. We did not identify factors correlated to malignant tumor. Analysis for survival: both IGCCCG class and malignant tumor at surgery were statistically significant in the multivariate analysis (p<0.001), whereas size, Royal Marsdem Class or histology of the primary were not. Five-year survival was 75%, 93% and 95% if malignant tumor, teratoma or necrosis were found respectively. Good, intermediate and bad prognosis group had a 5-yr survival of 97, 87 and 81% respectively. Conclusions: Our results suggest that persistence of small lesions after chemotherapy together with teratomatous elements in the primary predicts teratoma at surgery. IGCCCG class and persistence of malignant cells at surgery are the strongest prognostic factors for survival after resection of residual masses. No significant financial relationships to disclose.

Mediastinal metastases from testicular nonseminomatous germ cell tumors: Patterns of dissemination and predictors of long-term survival with surgery

Objectives: The purpose of this study was to determine the pattern of mediastinal dissemination of nonseminomatous germ cell tumors of testicular origin and evaluate variables that may influence survival with mediastinal dissection in patients with metastatic nonseminomatous germ cell tumors. Methods: From 1981 to 2000, a total of 421 patients were seen at our institution for extirpation of residual lung or mediastinal disease after cisplatin-based chemotherapy for metastatic testicular nonseminomatous germ cell tumors. We reviewed 268 of these patients, with a mean age of 26.8 years, who required at least one surgical procedure to remove residual mediastinal disease. Pathologic types of resected residual mediastinal disease were necrosis (15%), teratoma (59%), persistent nonseminomatous germ cell cancer (15%), and non-germ cell carcinomatous degeneration (11%). Twelve variables were evaluated by univariate analyses, and four variables potentially statistically significant at P <.10 were subsequently entered into a Cox regression model. Results: All patients demonstrated metastases to the visceral mediastinum. Fewer patients also demonstrated metastases to the paravertebral sulcus or anterior compartments (16% and 7%, respectively). Overall 5- and 10-year survivals were 86% ± 2% and 74% ± 4%, respectively. According to multivariate analysis, disease-related survival was negatively influenced by an elevated preoperative β-human chorionic gonadotropin level (P =.028) and adverse pathologic characteristics of residual mediastinal disease (P =.006). Conclusions: Testicular nonseminomatous germ cell tumors follow a predictable pattern of mediastinal dissemination, primarily following the course of the thoracic duct and its major tributaries. Patients who require surgery to remove residual mediastinal disease after cisplatin-based chemotherapy for metastatic nonseminomatous germ cell tumors have good to excellent long-term survivals. These results justify an aggressive surgical approach, including multiple surgical procedures if clinically indicated.J Thorac Cardiovasc Surg 2003;125:913-23

Early nasogastric tube removal combined with metoclopramide after postchemotherapy retroperitoneal lymph node dissection for metastatic testicular nonseminomatous germ cell tumor

Objectives. To evaluate the efficacy of combining early nasogastric tube (NGT) removal and metoclopramide after postchemotherapy retroperitoneal lymph node dissection (RPLND) in decreasing complications, time to diet tolerance, and discharge. Methods. We performed a retrospective study of 31 patients who underwent postchemotherapy RPLND at the University of Texas M. D. Anderson Cancer Center between 1994 and 1996, who were treated with a clinical care pathway that included NGT removal on postoperative day 1 and immediate use of promotility agents such as metoclopramide. A comparison was made with 42 historic controls treated from 1988 to 1994 who were managed with an NGT until the return of flatus and minimal promotility agents. Results. Both groups had comparable age, chemotherapy, and surgical procedures. The study group had fewer complications, with an earlier tolerance of solid food (median 5 ± 2.5 days compared with 7 ± 5.1 days in controls, P = 0.000) and discharge (median 6 ± 2.6 days compared with 9 ± 6.9 days in controls, P = 0.000). NGT replacement was required in 3.2% of study patients versus 9% of controls. Multiple regression analyses demonstrated that the number of NGT days was an independent predictor of early return of bowel function and length of hospitalization ( P = 0.000), and metoclopramide was not. Conclusions. Early NGT removal combined with metoclopramide after postchemotherapy RPLND allowed earlier diet tolerance and shortened hospital stays without increased complications. The role that promotility agents play as a necessary component of safe, early NGT removal is unclear.

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era

The current study reviews chronologic changes in the long term outcome of patients with metastatic nonseminomatous testicular germ cell tumors (NSTGCT) who were treated at a single institution during the past two decades. The 10-year survival of prognostic subgroups according to the classification of the International Germ Cell Consensus Classification Group (IGCCCG) and various other prognostic classifications is examined in time to evaluate whether cumulative experience has led to an improved outcome of patients with metastatic NSTGCT and to explore differences in outcome of prognostic subgroups. Two hundred ninety-nine patients with metastatic NSTGCT who were treated with cisplatin-based polychemotherapy during the period from 1977 to 1996 were staged retrospectively according to the Royal Marsden (RM) classification and the following prognostic classifications: IGCCCG, Indiana, Medical Research Council (MRC), and European Organization for Research and Treatment of Cancer (EORTC). The numbers of patients who were treated during the periods 1977-1986 and 1987-1996 were 146 and 153, respectively. Survival curves were constructed using the Kaplan-Meier method, and disease specific 10-year survival rates of prognostic subgroups treated during the two consecutive 10-year periods were compared using the log rank test. The median follow-up of surviving patients during the periods 1977-1986 and 1987-1996 was 14.7 years (range, 0.2-20.6 years) and 7.0 years (range, 0.4-11.4 years), respectively. The actuarial disease specific 10-year survival rate of patients with metastatic NSTGCT increased from 76% during the period 1977-1986 to 88% during the period 1987-1996 (relative risk [RR], 0.51; 95% confidence interval [95% CI], 0.29-0.89; P < 0.05). The 10-year survival rates of patients with good, intermediate, and poor prognoses according to the IGCCCG classification were 95%, 74%, and 37%, respectively, during the period 1977-1986 and 94%, 87%, and 66%, respectively, during the period 1987-1996. Patients with a poor prognosis according to the IGCCCG classification showed the greatest increase in 10-year survival (RR, 0.43; 95% CI, 0.18-1.04; P = 0.06). Analysis using the RM, Indiana, and EORTC classifications also showed an improved 10-year survival rate of patients with a poor prognosis who were treated during 1987-1996 compared with those who were treated during 1977-1986. The 10-year survival rate of patients with metastatic NSTGCT who were treated with cisplatin-based chemotherapy significantly increased from 76% during the period 1977-1986 to 88% during the period 1987-1996. This improvement during the cisplatin era resulted mainly from an increase in the survival of patients with metastatic disease who had a poor prognosis. These results indicate that the management of patients with NSTGCT is still improving.

First-Line High-Dose Chemotherapy for ’Poor Risk’ Metastatic Non-Seminomatous Testicular Germ Cell Tumors

First-Line High-Dose Chemotherapy for ’Poor Risk’ Metastatic Non-Seminomatous Testicular Germ Cell Tumors