Nonseminomatous Germ Cell Tumor Patients Research Articles

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.

The prognostic impact of different tumor marker levels in nonseminomatous germ cell tumor patients with intermediate prognosis: A registry of the International Global Germ Cell Tumor Collaborative Group (G3)

BackgroundGerm cell tumor patients with intermediate prognosis (IPGCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification represent a heterogeneous group with different clinical features. This analysis was performed to investigate the prognostic impact of different tumor marker levels prior to first line chemotherapy within IPGCT. MethodsFor this study an international registry for IPGCT was established. Eligibility criteria were intermediate prognosis according to IGCCCG criteria, nonseminomatous histology, male sex, and age ≥ 16 years. Uni- and multivariate analysis were conducted to identify characteristics associated with survival outcomes. Receiver-Operating-Characteristic curve analysis was applied to find cut-off parameters. Five-year overall survival (OS) rate was the primary and 5-year progression-free survival rate the secondary endpoint. ResultsThis database included 634 IPGCT with a median follow-up of 9.0 years (interquartile range: 14.35). Patients received first line treatment with platinum based chemotherapy, associated with a 5-year OS rate of 87%. The stratification of patients according to AFP levels revealed a correlation between AFP levels and outcome, associated with 5-year OS rates of 88% for AFP levels <1,000 IU/ml (n = 303), 89% for 1,000 to 2,000 IU/ml (n = 82), 87% for >2,000 to 6,000 IU/ml (n = 121), and 82% for >6,000 IU/ml (n = 57) prior first course of chemotherapy, respectively (P= 0.013). LDH levels prior fist course of chemotherapy also correlated with outcome associated with 5-year OS rates of 92% for <2 UNL (n = 271), 89% for ≥2 to 3 UNL (n = 85), 78% for >3 to 4 UNL (n = 34), and 77% for >4 UNL (n = 79), respectively (P= 0.03). Different HCG levels prior chemotherapy were not associated with outcome. In multivariable analysis AFP levels >6,000 IU/ml (P= 0.023; hazard ratio HR 2.263) or >1,982 IU/ml (P= 0.031; HR 1.722), and LDH levels >3 UNL (P< 0.001; HR 2.616) were independent prognosticators for OS. ConclusionsPrognostication according to LDH and AFP levels prior chemotherapy could offer a new approach to stratify patients within the intermediate prognosis cohort. According to our findings, patients with AFP values above 6,000 IU/ml or/and LDH > 3 UNL represent an independent high risk cohort.Our results need to be confirmed in the upcoming IGCCCG reclassification.

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.

Dose-reduced first cycle of chemotherapy for prevention of life-threatening acute complications in nonseminomatous germ cell tumor patients with ultra high tumor markers and/or poor performance status.

Patients with metastatic nonseminomatous germ cell tumors (mNSGCT) and a high tumor burden or a poor performance status at initial diagnosis are at risk from potentially life-threatening early complications during or after the first chemotherapy cycle. The outcomes with dose-reduced first cycle of chemotherapy in this population of patients are not well established. We performed a retrospective analysis of patients with mNSGCT and International Germ Cell Cancer Collaborative Group (IGCCCG) poor risk features. All patients received cisplatin and etoposide-based combinations as first-line treatment. Ultra high tumor marker levels were defined as α-fetoprotein ≥ 100,000ng/ml or human chorionic gonadotropin ≥ 200,000mIU/ml. Before 2005, the first treatment cycle was administered at a full dose in our center. After 2005, we used an abbreviated course of cisplatin and etoposide (EP) for the first cycle, followed by subsequent full-dose administration. From 1987 to 2012, 265 patients with poor risk features according to IGCCCG received first-line chemotherapy. Among them, 63 out of 265 (24%) patients had ultra high tumor marker levels and/or ECOG performance status of 3-4. Dose reduction of the first chemotherapy cycle was associated with a significant decrease of life-threatening complications from 76 to 44% (p = 0.01), but not with the overall survival (HR 0.99, 95% CI 0.44-2.26). Dose reduction of the first EP cycle by 40-60% in the subgroup of poor risk patients with ultra high tumor marker levels and/or ECOG performance status 3-4 is associated with significantly lowered acute complication rates but not with overall survival.

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.

Serum miRNA to predict post-chemotherapy viable disease in testicular non-seminomatous germ cell tumor patients.

546 Background: Retroperitoneal lymph node dissection (RPLND) is recommended for residual masses &gt; 1cm post-chemotherapy (pc) for nonseminomatous germ cell tumors (NSGCT). There is no reliable predictor for pcRPLND histology and up to 50% will harbour necrosis/fibrosis only, thus rendering a potentially morbid surgery to be of limited therapeutic value. Objective: To evaluate the ability of defined serum microRNA (miRNA) using the ampTSmiR test to predict residual viable NSGCT after chemotherapy. Methods: Serum miRNA levels (miR-371a-3p, miR-373-3p and miR-367-3p) were measured in 82 patients (cohort A = 39, cohort B = 43) treated with orchiectomy, chemotherapy and pcRPLND to predict viable GCT post-chemotherapy. Outcomes, measurements and statistical analysis: miRNA levels were compared to clinical characteristics, serum tumor markers and correlated with presence of viable GCT (vs. teratoma; vs. necrosis/fibrosis). miRNA-discriminative capacity was determined by receiver operating characteristic (ROC) analysis. Results: Serum miRNA were associated with stage at the time of chemotherapy and declined significantly post-chemotherapy. Patients with fibrosis/necrosis and teratoma had a significant decline in all three miRNA levels after chemotherapy, while those with viable disease had very little change. Patients with necrosis/fibrosis demonstrated similar miRNA levels as patients with residual teratoma. miR-371a-3p demonstrated the highest discriminative capacity [area under the curve (AUC) 0.874, CI 95% 0.774 - 0.974 p &lt; 0.0001] for viable disease post chemotherapy. If considering a more relaxed cut-point of 3cm before consideration of pcRPLND, miR-371a-3p correctly stratified all patients with residual retroperitoneal lesions ≤ 3 cm ( p= 0.02; 100% sensitivity). Conclusions: Our study is the first to explore a miRNA-based serum test to determine histology in post-chemotherapy residual masses and we demonstrated the value of miR-371a-3p to predict presence of viable GCT. Prospective studies are required to confirm its clinical utility.

Growing teratoma syndrome: Is it a subtype of germ-cell tumors or another entity?

e16040 Background: Growing teratoma syndrome(GTS ) is a process presenting with growing masses despite normal tumor marker levels(TML) after chemotherapy in non-seminomatous germ cell tumors (NSGCT). Methods: GTS patients between 2000-2016 were evaluated for clinicopathological features and survival outcomes retrospectively. Results: 17 (6,4%) of 266 NSGCT had GTS. Median follow-up was 57.7 ( 13.8-132.7) months. Median age 27 (17-51) years . Most (n = 14) of them had mixed germ-cell tumors &amp; 12 had mature/immature teratoma in primary pathology at diagnosis. Most (n = 11) of them had stage 3 disease &amp; 10 had high TML (S1-3). 11 GTS patients had good risk NSGCT. All (n = 17) had 4 BEP(bleomycin, etoposide, cisplatin) cycles. Recurrence occured in retroperitoneum (n = 13), lung (n = 3) &amp; brain (n = 1). They were considered as GTS since they had normal TML despite growing masses. 5 patients were referred to surgery without salvage chemotherapy and they had teratoma on postoperative surgery. 13 had surgery after salvage chemotherapy (TIP: taxane, ifosfamide, platin) but 4 had unresectable disease and they had clinical benefit with interferone α2b. Two operated patients had diffuse necrosis on pathology whereas others had documented teratoma. Median DFS was 12.3 ( 5.7-18.8) months whereas median OS was 64.8 (15.5-158) months. 3 patients had no recurrence after surgery for GTS. 9 had salvage chemotherapy (gemcitabine/oxaliplatin, TIP) for NSGCT metastatic lesions with TML elevation and 2 of them had autolog stem cell transplantation. Conclusions: GTS is rare in NSGCT, but it should be considered in NSGCT patients with both growing masses &amp; normal TML after primary treatment approach. GTS patients surgery with resectable masses should be referred to surgery since teratoma without viable tumor seems to have less benefit from chemotherapy and/or radiotherapy. Interferon α2b might be an option in unresectable GTS.

Outcomes of surveillance versus adjuvant chemotherapy for patients with stage IA and IB nonseminomatous testicular germ cell tumors.

Currently, it is accepted that risk assessment of clinical stage I (CS I) nonseminomatous germ cell tumors (NSGCT) patient is mainly dependent on the presence of lymphovascular invasion (LVI). Initial active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND) are acceptable treatment options for these patients, but there is no uniform consensus. The purpose of this study was to compare outcomes of active surveillance with adjuvant chemotherapy. A total of 201 patients with CS I NSGCT after orchiectomy were included. Outcomes of active surveillance and adjuvant chemotherapy were retrospectively analyzed. The prognostic significance of risk factors for survival and relapse was evaluated. Of the 201 patients, 110 (54.7%) received adjuvant chemotherapy, while the remaining 91 patients (45.3%) underwent surveillance. Relapses were significantly higher for patients underwent surveillance compared to adjuvant chemotherapy group (18.3 vs. 1.2%, p<0.001). The 5-year relapse-free survival (RFS) rate for patients who were treated with adjuvant chemotherapy was significantly better than those of patients underwent surveillance (97.6 vs. 80.8%, respectively; p<0.001). Univariate analysis showed that the presence of LVI (p=0.01) and treatment option (p<0.001) were prognostic factors for RFS and pT stage (p=0.004) and invasion of rete testis (p=0.004) and the presence of relapse (p<0.001) were significant prognostic factors for OS. Multivariate analysis revealed that the treatment strategy was an independent prognostic factor for RFS (p<0.001, HR 0.54). A logistic regression analysis demonstrated that treatment options (p=0.031), embryonal carcinoma (EC) >50% (p=0.013) and tumor diameter (p=0.016) were found to be independent factors for predicting relapse. Our results indicate that adjuvant chemotherapy is associated with improved RFS compared with surveillance for CS I NSGCT patients. Moreover, the treatment strategy is an important prognostic indicator for RFS and a predictive factor for relapse. Although adjuvant chemotherapy seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still preferred management option.

The Biochemical and Pathological Correlates of Successful Semen Cryopreservation From Patients With Testicular Cancer: A Single Tertiary Center Experience

To determine the predictors for success with regard to semen cryopreservation and good semen quality of patients with testicular cancer. A total of 50 men (aged 16-36 years) with testicular cancer, referred for semen cryopreservation prior to gonadotoxic treatment, were included. Age, alpha fetal protein (α-FP), beta human chorionic gonadotropin, lactate dehydrogenase, clinical staging, tumor volume, and pathological reports were evaluated as correlates of successful semen cryopreservation and good semen quality. The overall success rate was 52%. α-FP (4113.1 ng/mL vs 81.2 ng/mL) and tumor volume (77.7 mL vs 25.5 mL) were significantly higher in the failure group as compared to the success group. The seminoma to nonseminomatous germ cell tumor ratio was lower in the failure group as compared to the success group (9/17 vs 3/21). There was nearly a significant difference (P = .066). The optimal cutoff value for α-FP > 1000 ng/mL showed the highest Youden index (0.689) and resulted in a sensitivity of 0.625 and specificity of 1.0 for predicting poor outcome. In terms of multivariate analysis, the α-FP (P = .013), tumor volume (P = .047), and α-FP > 1000 ng/mL (P = .010) were significantly associated with poor semen quality and failure to preserve semen. Sperm quality was found to be higher in the seminoma versus the nonseminomatous germ cell tumor patients in: sperm concentration (21.5 million/mL vs 11.8 million/mL, P < .027). Furthermore, tumor volume is correlated to α-FP (P = .018) and is weakly correlated to lactate dehydrogenase (P = .067) CONCLUSION: Elevated α-FP and tumor volume are independently poor factors for semen quality and semen cryopreservation. In clinical use, α-FP is a noninvasive tool to predict the success of semen cryopreservation and patients with α-FP > 1000 ng/mL should be informed of the higher risk of poor semen quality and semen cryopreservation concerns.

Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor.

To clarify the significance of the International Germ Cell Cancer Collaborative Group classification in the 2000s, especially in intermediate- and poor-prognosis testicular germ cell tumor in Japan. We retrospectively analyzed 117 patients with intermediate- and poor-prognosis testicular non-seminomatous germ cell tumor treated at five university hospitals in Japan between 2000 and 2010. Data collected included age, levels of tumor markers, spread to non-pulmonary visceral metastases, treatment details and survival. The median follow-up period of all patients was 57months. A total of 50 patients (43%) were classified as having intermediate prognosis, and 67 patients (57%) as poor prognosis according to the International Germ Cell Cancer Collaborative Group classification. As first-line chemotherapy, 92 patients (79%) received bleomycin, etoposide and cisplatin. Of all patients, 74 patients (63%) received second-line chemotherapy. The most commonly used second-line chemotherapy regimens were a combination of taxanes, ifosfamide and platinum in 49 cases (66%). Overall, 33 patients (28%) received third-line chemotherapy. A total of 88 patients (75%) underwent post-chemotherapy surgery. The 5-year overall survival for intermediate (n=50) and poor prognosis (n=67) was 89% and 83% (P=0.21), respectively. In poor prognosis patients, patients with two or more risk factors (any of high lactic dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin levels, and presence of non-pulmonary visceral metastases) had significantly worse survival than those with only one risk factor (71% and 91%, respectively, P=0.01). The 5-year overall survivals of poor-prognosis testicular non-seminomatous germ cell tumor patients reached 83%. Further stratification of poor-prognosis patients based on a number of risk factors has the potential to further identify those with poorer prognosis.

Outcomes of progression on surveillance for clinical stage I nonseminomatous germ cell tumours (NSGCT).

377 Background: Active surveillance (AS) is universally accepted for clinical stage (CS) IA and favoured by most centers for CSIB. Patients progressing on AS are typically treated with chemotherapy, but there is no consensus. We describe patterns and mode of detection of progression and treatment of progression in our NSGCT AS cohort. Methods: From Dec 1980 to Aug 2011, 466 CSI NSGCT patients were managed with AS and 133 (28%) had disease progression while on AS. Treatment upon progression was physician choice but based on site of progression (e.g. retroperitoneum vs. extra-retroperitoneal), size or multifocality, and markers (S0 or stable, low level S1 vs. ≥ S1). Mode of detection of progression, characteristics at progression and primary treatment of progression (chemotherapy vs. retroperitoneal lymphadenectomy (RPLND)) were explored. Multivariate logistic regression was used to explore factors associated with receipt of more than one therapy in treatment of progression after surveillance. Results: Median time to progression was 7.3 months and detected by routine imaging (47%), routine serum tumour markers (37%), or both (12%). Progression most frequently occurred in the retroperitoneum (67%). Following progression, first-line treatment was chemotherapy for 71 (53%), RPLND for 51 (38%) and 11 (8.3%) underwent other therapy. In 59%, only one modality of treatment was required: chemotherapy only in 42/71 (59%); RPLND only in 36/51 (71%). For those treated with chemotherapy, pure embryonal carcinoma in the orchiectomy pathology (OR 0.11; p=0.05) was inversely associated with requiring further therapy. For those treated with RPLND, elevated markers pre-RPLND (OR 7.31; p=0.01) was associated with requiring further therapy. Overall, a second relapse occurred in 25/133 (19%) patients. With a median follow-up of 8.2 years, there were 5 deaths from testis cancer (3.8% of AS progressors; only 1.1% of overall AS cohort). Conclusions: The majority of patients progressing on surveillance do so in the retroperitoneum and within the first year. Of those that progress, most will achieve complete response with single modality treatment. In particular, RPLND can be utilized as monotherapy in select cases.

Complex residual tumors after chemotherapy of nonseminomatous germ cell tumors. Laparoscopic management - limits and chances

Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is often required in patients with metastatic nonseminomatous germ cell tumors (NSGCT) and residual tumors after chemotherapy. Laparoscopy has become established as a safe procedure in the surgical management of these tumors. Due to the rapid development of laparoscopy, complex retroperitoneal and even intrathoracic residuals can also be treated in high volume centers. This study included 21 retrospectively identified NSGCT and seminoma patients (mean age 29 years) with metastatic disease and clinical stage (CS) IIA-IIIB. A bilateral L-RPLND was performed in all male patients between 2009 and 2014. In 19 patients an infiltration of the great vessels was detected during surgery and vascular reconstruction was necessary. In 2 patients an intrathoracic residual 5.4cm and 7cm in size, respectively, was diagnosed during follow-up. Exclusion criteria for L-RPLND were positive tumor markers after chemotherapy, patients with local recurrence after previous open L-RPLND and patients with excessive vascular involvement. In this series no conversions to open surgery were necessary. The mean tumor size post-chemotherapy was 3.6cm (range 1.5-9.7cm). The mean measured blood loss was 294ml (range 50-1000ml). The mean hospitalization time was 6 days (range 3-9 days) and mean follow-up was 16 months (range 1-37 months). No complications higher than grade II (Clavien-Dindo classification) were registered in the immediate postoperative course. During the follow-up period no in-field recurrences were registered. The L-RPLND seems to be a safe alternative surgical procedure for certain complex residuals with vascular involvement after chemotherapy of testicular cancer. Bilateral L-RPLND is technically feasible and reproducible under guaranteed oncological principles. An infiltration of the great vessels and also intrathoracic residuals can be managed in selected patients without compromising the clinical and oncological course.

Postchemotherapy Laparoscopic Retroperitoneal Lymph Node Dissection for Nonseminomatous Germ Cell Tumors Infiltrating the Great Vessels

Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is an alternative in patients with metastatic nonseminomatous germcell tumors (NSGCT) necessitating resection of residuals postchemotherapy. With the advancement of laparoscopic vascular surgery, prospective management of the great vessels has become feasible and safe. We present our experience with L-RPLND in NSGCT residuals with significant vascular involvement necessitating intracorporeal reconstruction. We have retrospectively identified 19 NSGCT patients (mean age 27 years) who presented with residuals postchemotherapy. A bilateral L-RPLND was performed in all men. Infiltration of the great vessels was confirmed intraoperatively. Prospective vascular control and temporary clamping was performed in all cases. The vessel wall was reconstructed using vascular surgery techniques. All patients had at least clinical stages of IIA or higher. Follow-up was obtained in all. There were no conversions to open surgery. The mean size of the residuals after chemotherapy was 3.87 cm (1.5-9.7 cm). The mean blood loss was 310 mL (50-1000 mL). Mean hospital stay was 6 days (3-9 days). There were no perioperative complications exceeding grade II according to the Clavien-Dindo classification. Distant or in-field recurrence (mean observational period 18 months) did not develop in any patient. Laparoscopic RPLND may be considered a safe alternative concept for the management of post-chemotherapy NSGCT residuals involving the great vessels. Bilateral L-RPLND in patients with vascular infiltration is feasible and reproducible when laparoscopic vascular surgery can be reliably handled. All standard principles of open surgery are respected, and initial oncologic results are promising.

Optimal Management of Clinical Stage I Testis Cancer: One Size Does Not Fit All

Optimal Management of Clinical Stage I Testis Cancer: One Size Does Not Fit All

Postchemotherapy Residual Masses in Nonseminomatous Germ Cell Tumor Patients: 18F-FLT PET Is Unlikely to Identify Mature Teratoma, but Imaging of αvβ3 Integrin Expression Could

TO THE EDITOR: In a recent study comparing 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) and 18F-FDG for therapy monitoring in 11 nonseminomatous germ cell tumor (NSGCT) patients, Pfannenberg et al. ([1][1]) reported 2 patients in whom resected residual masses contained mature teratoma and harbored

Assessment of immature teratoma by 18F-FDG PET/CT

Teratomas are the most frequent extra-gonadal non-seminomatous germ cell tumors (NSGCTs). Retroperitoneum is the third most common site for teratomas and 30–40% of them may have immature tissue. The use of 18F-FDG PET in NSGCTs has been recently investigated. Here we report a 22 year-old male patient with metastatic immature teratoma, followed by PET/CT according to the existence of 18F-FDG avid metastatic lesions. According to our experience, functional imaging with PET/CT has an additive effect to anatomical imaging modalities in NSGCT patients when the tumoral tissue contains more primitive immature elements.

Survival After Resection for Metastatic Testicular Nonseminomatous Germ Cell Cancer to the Lung or Mediastinum

Since the advent of cisplatin-based chemotherapy, nonseminomatous germ cell tumors (NSGCT) have been considered one of the most curable solid neoplasms and a model for multimodality cancer therapy. We undertook an institutional review of testicular NSGCT patients who underwent operations to remove lung or mediastinal metastases after chemotherapy in the cisplatin era to determine outcomes. From 1980 to 2006, 431 patients underwent 640 postchemotherapy surgical procedures to remove lung (n = 159, 36.8%), mediastinal (n = 136, 31.6%), or both lung and mediastinal (n = 136, 31.6%) metastases within 2 years of chemotherapy. Multiple variables potentially predictive of survival were analyzed. The overall median survival was 23.4 years, with 295 (68%) patients alive and well after an average follow-up of 5.6 years. There was no survival difference in patients who underwent removal of lung or mediastinal metastases. Pathologic categories of resected residual disease were necrosis (21.5%), teratoma (52.7%), persistent NSGCT (15.0%), and degenerative non-germ cell cancer (10.1%). Multivariable analysis identified older age at time of diagnosis (p = 0.001), non-germ cell cancer in testes specimen (p = 0.004), and pathology of residual disease (p < 0.001) as significantly predictive of survival. Patients who undergo resection of residual lung or mediastinal disease for metastatic testicular NSGCT as a planned approach after cisplatin-based chemotherapy have overall excellent long-term survival. Survival is equivalent comparing hematogenous and lymphatic routes of metastases but depends on the pathology of the resected disease. These results justify an aggressive surgical approach, particularly to remove residual teratoma in the lung or mediastinum after chemotherapy, including multiple surgical procedures if necessary.

Retroperitoneal Lymph Node Dissection with No Adjuvant Chemotherapy in Clinical Stage I Nonseminomatous Germ Cell Tumours: Long-Term Outcome and Analysis of Risk Factors of Recurrence

BackgroundThe best management for patients with clinical stage I (CS1) nonseminomatous germ cell tumours (NSGCT) is still under debate. ObjectiveWe evaluated the long-term oncologic outcome of retroperitoneal lymph node dissection (RPLND) in patients with CS1 NSGCTs and reevaluated the traditional predictors of recurrence in a set of patients not undergoing adjuvant treatment. Design, setting, and participantsBetween 1985 and 1995, 322 consecutive CS1 NSGCT patients underwent primary RPLND not followed by adjuvant chemotherapy in a single referral centre. Patients were followed until relapse for a median time of 17 yr. MeasurementsWe estimated the crude cumulative incidence of any recurrence. Categories pN and pT, vascular invasion (VI), percentage of embryonal carcinoma, and presence of teratoma were evaluated as 2-yr recurrence predictors of event in a binary logistic model. Results and limitationsFifty patients had a recurrence (46 in ≤2 yr and only 4 [1.2%] in >2 yr). The 10-yr recurrence incidence was 15.2%. Significant predictors of recurrence at multivariable analysis were pN+, pT >1, and the presence of VI. However, the discriminative ability of the model was modest (Harrell C=0.74); only 9% and 3% of patients had a predicted recurrence probability >30% and >50%, respectively. ConclusionsRPLND alone could prevent recurrence in 85% of patients and minimise late relapses to 1.2%. Most patients could avoid the immediate and late toxicity of chemotherapy. Prognostic parameters combined into the multivariable model appeared of limited use in identifying a subset of patients at high risk of recurrence.

Salvage chemotherapy with methotrexate, etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: A preliminary report

The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high-dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of ß-human chorionic gonadotropin (ß-HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1–5, etoposide: 100 mg/body on days 1–5) was subsequently administered. After MEA therapy (median: 3 cycles), serum ß-HCG was normalized in five of the nine patients. Of these five, three achieved long-term disease-free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of ß-HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment-related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.

Prediction of Retroperitoneal Histology in Metastatic Nonseminomatous Testicular Cancer Patients after Chemotherapy Based on Clinical and Radiological Parameters

Introduction: We retrospectively analysed the predictive value of numerous clinical and radiological parameters to identify a predictor for either necrosis or residual tumors found by retroperitoneal lymph node dissection (RPLND) histology in a collection of nonseminomatous germ cell tumor (NSGCT) patients. Materials and Methods: A database was created containing detailed clinical, radiological and histological information of all consecutive NSGCT patients, who underwent post chemotherapy RPLND between 1984 and 2007. According to the histology of the RPLND specimen, patients were assigned to the “necrosis-only” group or the “residual tumor” group. Associations between clinical and radiological parameters and histology of RPLND were analyzed. Results: Histology of dissected masses showed complete necrosis in 57.4% of patients and residual tumors in 42.6% (3.1% viable cancer and 39.5% teratoma). Univariate analysis showed significant correlation of RPLND histology and the following parameters: teratoma-positive primary tumors, pre-chemotherapy α-fetoprotein (AFP) and – less pronounced – human chorionic gonadotropin levels, size of metastatic mass, total volume of metastatic retroperitoneal lymph nodes, and percentage of volume reduction. The best prediction for necrosis in RPLND histology was in patients with no evidence of teratomatous elements in primary tumors and with normal pre-chemotherapy AFP levels and small lymph nodes. Stepwise multivariate logistic regression analysis confirmed AFP < 10 ng/ml as the best independent predictor for only necrosis in RPLND histology. Conclusions: At the present time we still consider all patients with metastatic NSGCT as candidates for a post-chemotherapy RPLND, arguing that in experienced hands mortality is negligible and morbidity is low and therefore not relevant compared to the risk of missing a residual tumor.