Metastatic Nonseminomatous Germ Cell Tumors Research Articles

V06-04 ROBOT ASSISTED INFERIOR VENA CAVOSCOPY

You have accessJournal of UrologyAdrenal, Testis, UTUC Oncology & More1 Apr 2018V06-04 ROBOT ASSISTED INFERIOR VENA CAVOSCOPY Haidar Abdul-Muhsin, Anthony Chau, Richard Fowl, and Erik Castle Haidar Abdul-MuhsinHaidar Abdul-Muhsin More articles by this author , Anthony ChauAnthony Chau More articles by this author , Richard FowlRichard Fowl More articles by this author , and Erik CastleErik Castle More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1583AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Conventional therapy of inferior vena cava tumor invasion (IVC) retroperitoneal malignancies involves caval resection with or without vascular grafting. Assessment of the extent of tumor invasion relies on preoperative (CT and MRI) and intraoperative (US) imaging. However, these imaging modalities cannot differentiate between bland and tumor thrombi. In this video we are presenting a technique for direct visualization of the IVC lumen to assess for tumor invasion during a robot assisted retroperitoneal lymph node dissection for testicular cancer. METHODS A 29 year old male patient with metastatic non-seminomatous mixed germ cell tumor was found to have a persistent metastatic retroperitoneal lymph node mass following four cycles of BEP chemotherapy. Preoperative imaging demonstrated a 6 cm interaortocaval mass with adjacent filling defect in the IVC. Preoperative imaging could not differentiate between tumor invasion vs bland thrombus. RESULTS After induction of general anesthesia, the patient was placed in a modified lithotomy position. Following port placement and robot docking, the small bowel was retracted cephalad and to the left upper quadrant. The retroperitoneal space was developed. Retroperitoneal lymph node dissection was started in a regular manner. The large mass was encountered in the interaortocaval region and was adherent to the IVC wall. It was dissected free from all attachments except the IVC wall. Proximal and distal control was obtained with vessel loops. A small venotomy was made on the IVC anterior wall just distal to the mass. A flexible cystoscope was introduced through one of the assistant ports and into the IVC lumen. Examination of the IVC showed multiple synechiae and vascular webs consistent with organized and recanalized bland thrombus with no evidence of tumor invasion. Given these findings no caval resection was needed. These webs were excised and the remaining part of the wall reconstructed, preserving more than 50% of the IVC circumference. The remaining part of the dissection was completed in the conventional manner. Operative time was 383 min, EBL was 150 ml, and LOS was one day. Postoperatively patient had smooth recovery with no postoperative complication. Postoperative pathology was consistent with a bland thrombus. Follow up imaging showed preserved IVC circumference and no filling defects. CONCLUSIONS Direct visualization of the IVC lumen is feasible using conventional endoscopic instruments and robotic approach. This helps avoid a large venotomy or graft placement and completion of the retroperitoneal lymph node dissection in a minimally invasive manner. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e662 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Haidar Abdul-Muhsin More articles by this author Anthony Chau More articles by this author Richard Fowl More articles by this author Erik Castle More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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.

A New Model to Predict Benign Histology in Residual Retroperitoneal Masses After Chemotherapy in Nonseminoma

BackgroundPostchemotherapy retroperitoneal lymph node dissection (pcRPLND) is indicated in testicular cancer patients with normalised or plateaued serum tumour markers and residual retroperitoneal lesions >1cm. Challenges remain in predicting postchemotherapy residual mass (pcRM) histology, which may lead to unnecessary surgery. ObjectiveTo develop an accurate model to predict pcRM histology in patients with nonseminomatous germ cell tumours (NSGCTs). Design, setting, and participantsA retrospective review of 335 patients undergoing pcRPLND for metastatic NSGCTs to develop a model to predict benign histology in retroperitoneal pcRM. Our model was compared with others and externally validated. InterventionChemotherapy and pcRPLND. Outcome measurements and statistical analysisMultivariable logistic regression to evaluate the presence of benign histology, and fractional polynomials to allow for a nonlinear association between continuous variables and the outcome. The final Princess Margaret model (PMM) was selected based on the number of variables used, reliability, and discriminative capacity to predict benign pcRM. Results and limitationsPMM included the presence of teratoma in the orchiectomy, prechemotherapy α-fetoprotein, prechemotherapy mass size, and change in mass size during chemotherapy. Model specificity was 99.3%. Compared with Vergouwe et al’s model, PMM had significantly better accuracy (C statistic 0.843 vs 0.783). PMM appropriately identified a larger number of patients for whom pcRPLND can safely be avoided (13.9% vs 0%). Validated in external cohorts, the model retained high discrimination (C statistic 0.88 and 0.80). Larger and prospective studies are needed to further validate this model. ConclusionsOur clinical model, externally validated, showed improved discriminative ability in predicting pcRM histology when compared with other models. The higher accuracy and reduced number of variables make this a novel and appealing model to use for patient counselling and treatment strategies. Patient summaryPrincess Margaret model accurately predicted postchemotherapy benign histology. These results might have clinical impact by avoiding unnecessary retroperitoneal lymph node dissection and consequently changing the paradigm of advanced testicular cancer treatment.

Modified retroperitoneal lymph node dissection for post-chemotherapy residual tumour: a long-term update.

To update previously reported outcomes of modified-template post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in appropriately selected patients with metastatic non-seminomatous germ cell tumour (NSGCT), as our previous report was criticised for short follow-up and so we now provide a long-term update on this cohort. In all, 100 patients with normal serum markers after cisplatin-based chemotherapy and residual retroperitoneal tumour underwent modified PC-RPLND between 1991 and 2004. Using a prospectively managed institutional testicular cancer database, long-term follow-up was obtained. As previously reported, 43 patients underwent a right-modified template, 18 patients underwent a full-left-modified template, and 39 patients underwent a left-modified template. The updated long-term median follow-up for the entire cohort is 125 months. Seven patients developed recurrent disease with a median (range) time to recurrence of 11 (6-102) months, and one patient died from recurrent disease in the chest 4 years after surgery. All recurrences were outside the boundaries of a full-bilateral template RPLND, with the most common location of recurrence being the chest. The 5- and 10-year recurrence-free survival rates were 93% and 92%, respectively. The overall survival at 10 years was 99%. In appropriately selected patients with low-volume disease before and after chemotherapy, a modified template has durable long-term efficacy without risk of in-field recurrences at a median follow-up of 125 months.

Validation of a prediction model for avoiding post-chemotherapy retroperitoneal lymphadenectomy in patients with metastatic nonseminomatous germ cell cancer.

Post-chemotherapy residual masses (PCRMs) may contain persistent cancer or teratoma in more than 50% of patients with metastatic non-seminomatous germ cell tumours (mNSGCTs). Retroperitoneal lymph node dissection (RPLND) is curative, but controversy exists about selection criteria for surgery. A validated prediction model by Vergouwe et al (2007) based on over 1000 patients was evaluated at our centre. mNSGCT patients treated with RPLND for PCRMs were identified from an electronic database. Typographical errors in the model were identified and corrected using their 2003 publication, but retaining the 2007 coefficients. Six clinical variables were included in the model and the calculated probability of benign tissue was compared with pathology. "Benign tissue only" was considered a positive test outcome in patients with a predicted probability of "benign tissue only" greater than 70%. Fifty-two (52) mNSGCT patients between 1980 and 2014 were evaluable. Median age was 32 years (range 17-52) and International Germ Cell Consensus Classification (IGCCC) prognostic stages were: good 46.2%, intermediate 32.7%, and poor 21.2%. Most patients received bleomycin/etoposide/cisplatin (BEP) chemotherapy and full bilateral RPLND. Pathology showed residual cancer or teratoma in 31 patients (59.6%) and benign findings in 21 patients (40.6%). Positive and negative predictive values and accuracy were 100%, 69%, and 73%, respectively. "Benign tissue only" was found in 100% of patients in whom this was predicted using our pre-determined criteria. This study involved a limited number of patients, but confirms the potential value of the Vergouwe et al model. Routine use of this prediction model in clinical practice should be tested for mNSGCT patients with PCRMs.

A Statistical Approach to Determine the Optimal Duration of Post-Treatment Follow-Up: Application to Metastatic Nonseminomatous Germ Cell Tumors

BackgroundThe objective of this study was to present a statistical method to define an optimal duration of follow-up for patients in remission after treatment for cancer, for detection of recurrences. Patients and MethodsSurveillance duration was estimated using the 2-step approach proposed by Mould et al. Relapse-free interval was modeled using the parametric cure model proposed by Boag. The optimal length of follow-up was then estimated as the minimal elapsed time after which the probability of a patient to relapse and to be cured with success is below a given threshold value. The method is applied to 2 real data sets of patients treated for metastatic non seminomatous germ-cell tumors: T93BP and T93MP. ResultsFor the T93BP, cure rate was estimated at 91.3% and proportions of patients who relapsed after 3 and 5 years were estimated at 0.5% and 0.2%. With a probability of success of salvage treatment equal to 80% and 50%, numbers of delayed cases after 5 years were 2 and 1. For T93MP, the proportion of patients who presented relapse after 5 and 10 years were estimated at 5.2% and 2.6%. Considering a probability of salvage treatment equal to 20%, the number of delayed cases after 5 and 10 years were 10 and 5. ConclusionUsing this methodology, duration of post-therapeutic follow-up might be tailored according to an objective criteria: the number of patients who present relapse after the end of follow-up and who could have been treated with success in case of early detection.

Surgical controversies in the management of post-chemotherapy nonretroperitoneal residual disease in metastatic nonseminomatous germ cell tumors.

Following the advent of platinum-based chemotherapy, Surgery, excepting orchidectomy, has become an adjunct treatment in the management of metastatic non-seminomatous germ cell tumors (NSGCT). Role of surgery comes into play in metastatic NSGCT when residual disease persists following standard chemotherapy. Surgical excision of all post chemotherapy residual disease at all places, whenever surgically feasible with acceptable morbidity and mortality, should be undertaken. As histopathological examination of the excised postchemotherapy residue shows only necrosis and fibrosis in significant number of patients; surgical exercise in this group of patients seems futile and unwarranted retrospectively. This issue becomes more contentious when surgeons are confronted with multiple nonretroperitoneal post chemotherapy residues. This article aims to deal with the management of postchemotherapy nonretroperitoneal residues in metastatic NSGCT.

Expression of P40 and P63 in lung cancers using fine needle aspiration cases. Understanding clinical pitfalls and limitations

Fine-needle aspiration (FNA) biopsy of lung lesions is a highly accurate method for diagnosing and staging of lung cancers, particularly in patients with advanced cancer. Although, the majority of FNA cases of non-small cell lung carcinoma (NSCLC) can be subclassified by hematoxylin and eosin (H&E) sections, immunohistochemical (IHC) markers are usually necessary for difficult cases. Our previous study has shown that both P40 and P63 demonstrate differential sensitivity and specificity in the subclassification of squamous cell carcinoma (SqCC) using tumor tissue microarrays (TMA). In the present study, we further evaluated the utility of P40 and P63 and the potential pitfalls and limitations associated with the usefulness of these stains in FNA cases. By a computer search of pathology archives, 144 FNA biopsies with diagnoses of lung cancers and P40/P63 stains were identified, including 50 adenocarcinomas (ADCs), 56 SqCCs, 8 small cell lung carcinomas (SCLCs), and 12 cases of poorly differentiated carcinoma (PD CA). Ten benign FNA lung lesions and 8 other malignant neoplasms were also included as controls. Nuclear staining patterns of P40 and P63 were scored semi-quantitatively as 0 (negative), 1 (<10%, weak and focal), or 2 (>10%, strong and diffuse). In lung SqCCs, P40 and P63 were positive in 77.3% and 89.5% cases, respectively. In ADCs, P40 was weakly and focally positive in 6.1% cases, and P63 was variably positive in 62.8% cases. In SCLCs, P40 and P63 were focally positive in 12.5% and 50% cases. In PD CAs, no P40 or P63 immunoreactivity was detected. In the group of other neoplasms (n=8) both P40 and P63 were positive in the case of metastatic non-seminomatous germ cell tumor (NSGCT) (n=1), and P63 was positive in the case of metastatic Merkel cell carcinoma (n=1). The sensitivity and specificity of P40 and P63 were 76.9%/93.3%, and 90.2%/50.7% in the lung SqCC. P63 has a better sensitivity, and P40 has a better specificity for SqCC. A positive staining pattern with both markers was also found in certain non-SqCC cases. Recognizing limitations of these markers are particularly important in FNA cases.

Low RBM3 protein expression correlates with clinical stage, prognostic classification and increased risk of treatment failure in testicular non-seminomatous germ cell cancer.

BackgroundExpression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate with favourable clinicopathological parameters and prognosis in several cancer diseases. The aim of this study was to examine the expression and prognostic ability of RBM3 in patients with testicular non-seminomatous germ cell tumours (NSGCT).Patients and MethodsImmunohistochemical RBM3 expression was analysed in tissue microarrays with tumours from 206 patients. Chi-square test was applied to analyze associations between RBM3 expression and clinicopathological parameters. Kaplan-Meier analysis was used to assess the impact of RBM3 expression on cancer-specific survival (CSS) and failure-free survival (FFS). Cox regression proportional hazards models were used to estimate the relative risk for failure.ResultsIn the entire cohort, there was a significant association between clinical stage (p=0.044) and RBM3 expression. Weak RBM3 expression correlated with a significantly reduced FFS [79.3% versus 90.4% (p=0.019)] and CSS [87.5% versus 97.3% (p=0.047)]. For patients with metastatic disease (n = 88), significant associations were found between RBM3 expression and IGCCC group (p=0.007). The FFS was significantly inferior for patients with low tumour-specific RBM3 expression [59.3% versus 79.0% (p=0.013)], and this association remained significant in a multivariable model for patients with metastatic disease (HR=3.67; 95% CI 1.14, 11.89).ConclusionLow RBM3 expression is an independent predictor of treatment failure in metastatic NSGCT, in relation to the prognostic factors included in the International Germ Cell Consensus Classification (IGCCC). These findings suggest that RBM3 may be a potential biomarker for treatment stratification in patients with metastatic non-seminomatous germ cell tumours, and therefore merit further validation.

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.

Low Rbm3 Protein Expression Correlates with Clinical Stage, Prognostic Index and Increased Risk of Treatment Failure in Testicular Non-Seminomatous Germ Cell Cancer

ABSTRACT Aim: Expression of the RNA-binding motif protein 3 (RBM3) has in previous studies been shown to correlate with favourable clinicopathological parameters and prognosis in a number of cancer forms. The aim of this study was to examine the expression and prognostic ability of RBM3 in patients with non-seminomatous germ cell tumours (NSGCT). Methods: Immunohistochemical RBM3 expression was analysed in tissue microarrays with tumours from 206 patients with NSGCT. Chi-square test was applied to analyze associations between RBM3 expression and clinicopathological parameters. Kaplan-Meier analysis was used to assess the impact of RBM3 expression on cancer-specific survival (CSS) and progression-free survival (PFS). Cox regression proportional hazards models were used to estimate the relative risk for progression in both uni- and multivariable analysis. Results: In the entire cohort, there was a significant association between clinical stage (p=0.044) and RBM3 expression. Low RBM3 expression correlated with a significantly reduced PFS [67.7% versus 87.8% (p=0.001)] and CSS [87.5% versus 97.3% (p=0.047)]. For patients with metastatic disease (n=88), significant associations were found between RBM3 expression and IGCCC prognostic index (p=0.007), combined tumor marker status (p=0.001) and HCG level (p=0.010). The PFS was significantly inferior for patients with low tumour-specific RBM3 expression [40.0% versus 73.0% (p=0.002)], and this association remained significant in a multivariable model (HR=2.98; 95% CI 1.14, 7.75). Conclusions: Low RBM3 expression is significantly associated with a worse IGCCC-prognostic index and is an independent predictor of disease progression in metastatic NSGCT. These findings suggest that RBM3 may be a potential biomarker for treatment stratification in patients with metastatic non-seminomatous germ cell tumours, and therefore merit further validation. Disclosure: All authors have declared no conflicts of interest.

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.

A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic non-seminomatous germ cell tumor

Approximately a quarter of men with metastatic non-seminomatous germ cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after chemotherapy. The management of small residual masses (≤1 cm) is controversial, with good outcomes seen with either post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) or surveillance. We sought to review our experience of surveillance and synthesize the cumulative findings with the current literature in the form of a meta-analysis. We searched PubMed, EMBASE and abstracts from ASCO and AUA to identify relevant, English-language studies for the meta-analysis. The DFCI (Dana Farber Cancer Institute) database was constructed from a database of men undergoing cisplatin-based chemotherapy for metastatic NSGCT. The outcomes of interest were the proportion with necrosis, teratoma or active cancer on histology at PC-RPLND (literature) and the total number of relapses, RP-only relapses and overall survival in men undergoing surveillance (literature and DFCI cohort). Three of 47 men undergoing post-chemotherapy surveillance at our institution relapsed over a median follow-up of 5.4 years. All three were alive at a median of 4.2 years after relapse. On meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in the 588 men who underwent PC-RPLND were 71, 24 and 4%, respectively. Of the combined 455 men who underwent surveillance, the pooled estimate of the relapse rate was 5%, with an RP-only relapse rate of 3%. Of the 15 men who suffered an RP-only relapse on surveillance, two died of disease. Surveillance is a reasonable strategy for men with minimal residual RP disease after chemotherapy and avoids an RPLND in ∼97% of men who are cured with chemotherapy alone.

Prediction of metastatic status in non-seminomatous testicular cancer

To examine the significance of 90 biomarkers for predicting metastatic status in non-seminomatous germ cell tumors (NSGCT). By predicting metastatic status, it may be possible to eliminate unnecessary therapeutic or diagnostic efforts. We investigated 552 males who were diagnosed with non-metastatic (n = 273) and metastatic (n = 279) NSGCT between 2000 and 2011. The sample included cancers of different histologies: embryonal cell carcinoma (n = 131), teratoma (n = 55), and mixed histology (n = 366). We collected and analyzed more than 90 parameters via logistic regression: demographic characteristics, medical history, histopathological parameters, and levels of tumor markers and hormones. Testis histology (p = 0.004), clinical symptoms (p = 0.0005), tumor length (p = 0.005), infiltration of the rete testis (p = 0.008), invasion of lymphatic (pL1) and blood vessels (pV1) (p < 0.0001), and levels of enzymes such as LDH, βHCG, AFP, and FSH (p values as small as <0.0001) were associated with metastatic status. With one model, we identified 14 out of 76 (18.4 %) metastatic NSGCT cases with 93-100 % certainty (positive predictive value) at 99 % specificity by the peripheral blood levels of LDH (day of operation) in combination with FSH measurements (1 day after operation). A second model included pV, tumor length, and FSH (1 day after operation). It identified 25 out of 90 (27.8 %) non-metastatic NSGCT with approximately 90 % certainty (negative predictive value) at 94-98 % sensitivity. No single parameter was able to discriminate metastatic from non-metastatic NSGCT, but combinations of parameters in two predictive models accurately identified the metastatic status in 23 % of the cases in our sample.

A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT).

324 Background: Around a quarter of men with metastatic nonseminatous germ cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after chemotherapy. While post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is accepted to be the best way to manage large retroperitoneal masses, the treatment of small residual masses (≤1cm) is controversial. Both PC-RPLND and surveillance produce good outcomes for men in this situation, and we sought to review our experience of surveillance and synthesize the cumulative findings in the form of a meta-analysis. Methods: We searched PubMed and abstracts from ASCO and AUA to identify relevant, English language studies. Inclusion criteria was the presence of a subcentimeter post-chemotherapy retroperitoneal mass. The Dana-Farber Cancer Institute cohort was constructed from a database of men undergoing cisplatin-based chemotherapy for metastatic NSGCT. The outcomes of interest were the proportion with necrosis, teratoma or active cancer on histology at PC-RPLND, and the total number of relapses, retroperitoneal (RP)-only relapses and overall survival in men undergoing surveillance. Results: A total of 47 men formed our surveillance cohort and three relapsed with a median follow-up of 5.4 years and median time to relapse of 12.7 months. All three were alive at a median of 4.2 years after relapse with salvage therapy. On meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in the 588 men who underwent PC-RPLND were 71%, 24% and 4% respectively. Of the combined 455 men who underwent surveillance, the pooled estimate of relapse rate was 5%, with an RP-only relapse rate of 3%. Overall, of the 15 men who suffered an RP-only relapse on surveillance, two died of disease. Conclusions: Surveillance is an alternative strategy for managing men with minimal residual RP disease after chemotherapy and avoids an RPLND in about 95% of men who are cured with chemotherapy alone.

Inferior Vena Cava Tumour Thrombus from Nonseminomatous Germ Cell Tumour Detected with F-18 FDG PET/CT

21-year-old male presented with recently diagnosed metastatic nonseminomatous germ cell tumour and left orchidectomy. CT demonstrated mixed density in the inferior vena cava (IVC) extending from the union of the common iliac veins to the level of the liver just below the confluence of the hepatic veins. Retroperitoneal nodal disease and deposits in the left lung were suspicious for metastatic deposits. F-18Flurodeoxyglucose (FDG) PET/CT images demonstrated avid FDG uptake within the lumen of the IVC from the level of the renal veins, with extension into both renal veins, to the level of T10. While benign and malignant thrombi have previously been demonstrated on F18-FDG PET imaging, this case highlights the use of F-18 FDG PET/CT when identifying tumour thrombosis in patients with nonseminomatous germ cell tumour.

Salvage Chemotherapy for Patients With Germ Cell Tumors: Is There a Best Regimen?

patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 25:247-256, 2007 6. de Wit R, Skoneczna I, Daugaard G, et al: Randomized phase III study comparing paclitaxel–bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: Intergroup Study EORTC 30983. J Clin Oncol 30:792-799, 2012 7. Kollmannsberger C, Daneshmand S, So A, et al: Management of disseminated nonseminomatous germ cell tumors with risk-based chemotherapy followed by response-guided postchemotherapy surgery. J Clin Oncol 28:537-542, 2010 8. Olofsson SE, Tandstad T, Jerkeman M, et al: 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. J Clin Oncol 29:2032-2039, 2011 9. Kris MG, Meropol NJ, Winer EP (eds): Accelerating progress against cancer: ASCO’s blueprint for transforming clinical and translational cancer research. http://www.asco.org/ASCOv2/Department%20Content/Cancer% 20Policy%20and%20Clinical%20Affairs/Downloads/Blueprint.pdf 10. Abernethy AP, Etheredge LM, Ganz PA, et al: Rapid-learning system for cancer care. J Clin Oncol 28:4268-4274, 2010 11. Frankovich J, Longhurst CA, Sutherland SM: Evidence-based medicine in the EMR era. N Engl J Med 365:1758-1759, 2011

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.