German Testicular Cancer Study Group Research Articles

Relapse-free and overall survival in patients with non-seminomatous testicular germ cell tumours with teratoma-free primaries.

421 Background: Characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate. Methods: We performed a retrospective analysis including 557 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". Results: Of the eligible 557 patients with NSGCT, 237 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 320 (58%) were teratoma-free. Teratoma-containing primaries had a significantly higher clinical stage (p=0.002) and worse prognosis (p=0.051) compared to teratoma-free specimens. Lymph node metastasis were significantly larger before (4.5 vs 2.5cm; p<0.001) and after chemotherapy (3.5 vs 2.5 cm; p<0.001) in teratoma-containing primaries. Post-chemotherapy retroperitoneal lymph node dissection was performed in 57% of all patients. As teratoma-containing specimens revealed a significantly lower number of complete responses after chemotherapy, PC-PRLND was more often performed, with teratomatous elements being more often present in the PC-RPLND specimens compared to non-teratoma containing primaries. Kaplan-Meier estimates revealed that 19% of all patients relapsed during a median follow-up of 56 months [29-112] with a median time to relapse of 10 months. Teratoma-containing had a significantly lower relapse-free survival (RFS) compared to teratoma-free NSGCT (relapse rate 24% vs 16%, p=0.020). 8% (45/533) of all patients died due to their disease. There was no difference regarding the tumour-specific survival between teratoma-containing NSGCT and teratoma-free NSGCT when looking at the entire cohort of patients (8% vs. 9%, p=0.563), however median overall survival was not reached. Conclusions: In our study, NSGCT patients with teratoma-containing primaries showed a significantly higher clinical stage and worse prognosis at time of presentation compared to teratoma-free primaries. Furthermore, patients with teratoma-containing primaries showed a significantly worse relapse-free survival. Consequently, treating physicians should be aware of these patients portending a dismal prognosis and the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

Association of nonseminomatous testicular germ cell tumors with teratoma-free primaries with disease relapse and overall survival.

422 Background: As the characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate, this study aims at evaluating recurrence-free and tumor-specific survival in this cohort of patients. Methods: We performed a retrospective analysis including 218 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". We analysed patient characteristics as well as follow-up of all included patients, being treated from 2000 to 2021. Results: Of the eligible 218 patients with NSGCT, 92 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 126 (58%) were teratoma-free. Kaplan-Meier estimates revealed that 28% of all patients relapsed during a median follow-up of 58 months [35-112] with a median time to relapse of 10 months. Teratoma-containing and teratoma-free NSGCT did not show a significant difference regarding the occurrence of relapse, however, teratoma-containing NSGCT had a significantly lower rate of early relapses ( < 24 months) compared to teratoma-free NSGCT (57% vs. 82%, p = 0.035). 14% (30/218) of all patients died due to their disease with a median time to death of 15 months, however median overall survival was not reached. There was no difference regarding the tumour-specific survival between teratoma-containing NSGCT and teratoma-free NSGCT when looking at the entire cohort of patients (11% vs. 16%, p = 0.299). However, in the group of intermediate or poor IGCCCG prognosis patients, tumour-specific survival was significantly worse in patients teratoma-free NSGCT compared to teratoma-containing specimens (16% vs. 35%, p = 0.040). Furthermore, patients with intermediate or poor IGCCCG prognosis showed a higher tumour-related mortality in pure teratoma-free primaries compared to patients with pure teratoma in the orchiectomy specimens (28% vs. 14%, p = 0.070). Here, pure embryonal carcinoma showed the highest relative mortality (80%). Conclusions: In our study, NSGCT patients with teratoma-containing primaries showed a significantly lower number of early relapses as well as a reduced tumour specific survival in intermediate and poor prognosis patients compared to teratoma-free NSGCT. Especially pure embryonal carcinoma patients revealed the highest rate of mortality. Consequently, treating physicians should be aware of these patients portending a dismal prognosis.

Peritoneal carcinosis in male germ cell tumor patients: a registry study compiled by the German Testicular Cancer Study Group (GTCSG)

PurposeTo report on the clinical characteristics, outcome, and frequency of peritoneal carcinosis (PC) in patients with advanced germ cell tumors (GCT), a multicenter registry analysis was carried out.MethodsA multicenter registry analysis was conducted by the German Testicular Cancer Study Group (GTCSG) with international collaborators. Data was collected and analyzed retrospectively. Patients were eligible for inclusion if PC was diagnosed either by radiologic or histopathologic finding during the course of disease. Descriptive and explorative statistical analysis was carried out with cancer-specific survival (CSS) as primary study endpoint.ResultsCollaborators from ten GCT expert centers identified 28 GCT (0.77%) patients with PC after screening approximately 3767 GCT patient files and one case was contributed from a cancer registry request. Patients were diagnosed from 1997 to 2019 at a median age of 37 years (interquartile range, 13). Two patients (7%) presented with stage I and 27 patients (93%) with synchronous metastatic disease at first diagnosis. The primary histology was seminoma in seven (27%) and non-seminoma in 21 patients (72%). PC was detected after a median of 15.3 months from primary diagnosis (range 0–177) and two consecutive treatment lines (range 0–5), respectively. The median CSS from the time of detection of PC was 10.5 months (95%Confidence Interval 0.47–1.30) associated with an overall 2-year CSS rate of 30%.ConclusionPC represents a rare tumor manifestation in GCT patients and was primarily associated with the occurrence of advanced cisplatin-refractory disease conferring to a dismal prognosis.

LBA30 Single-dose carboplatin followed by involved-node radiotherapy as curative treatment for seminoma stage IIA/B: Efficacy results from the international multicenter phase II trial SAKK 01/10

Standard treatment options for patients (pts) with seminoma clinical stage (CS) IIA/B are either extensive “dog-leg” para-aortic/pelvic radiotherapy (RT) or 3-4 cycles of cisplatin-based combination chemotherapy (ChT) with a 3-year progression free survival (PFS) of ≥90%, but potential acute and late toxicities. SAKK 01/10 is a trial of the Swiss Group for Clinical Cancer Research (SAKK) and the German Testicular Cancer Study Group (GTCSG) aiming at reducing therapy toxicity while preserving efficacy in CS IIA/B seminoma by combining deescalated ChT and RT.

Treatment compliance and early toxicity in SAKK 01/10: Single-dose carboplatin and involved-node radiotherapy for treatment of stage IIA/B seminoma.

405 Background: Standard treatment options for stage IIA/B seminoma include either extensive paraaortal/pelvic radiotherapy or intensive chemotherapy with 3x BEP or 4x EP. Both treatment modalities are associated with excellent efficacy but also a high rate of acute and late toxicities. Therefore, de-escalation strategies appear warranted for this patient group aiming to minimize acute and long-term toxicities while maintaining efficacy. SAKK 01/10 is a joint project of the Swiss Group for Clinical Cancer Research and the German Testicular Cancer Study Group. Methods: Patients with stage IIA/B seminoma (de novo or relapse on active surveillance) were eligible for participation in this single arm phase II trial. A repeat scan was advised in patients with equivocal lymph node enlargement. Treatment consisted of one cycle carboplatin AUC7 followed by involved-node radiotherapy with 30 Gy in stage IIA and 36 Gy in stage IIB disease. The primary endpoint of the trial is 3-year progression free survival. We report on treatment compliance and early toxicity during treatment and within 30 days. Results: 120 patients with stage IIA/B seminoma were recruited from 10/12 until 06/18 in 20 study centers in Switzerland and Germany. 116 patients were eligible and initiated treatment per protocol (40% stage IIA, 60% stage IIB). All patients received chemotherapy (CT) with a median applied dose of 984 mg (range: 560-1920 mg). The median planning target volume (PTV) for radiotherapy (RT) was 297 cm3 (range: 24-1047 cm3). RT was delayed/interrupted in two patients due to adverse events. During CT, grade 2 and grade 3 adverse events were seen in 21% and 2% of all patients respectively (most common grade 2 events: neutropenia 6%, nausea 5%). During RT, grade 2 and grade 3 adverse events were seen in 26% and 6% of all patients respectively (most common grade 2 events: neutropenia 15%, nausea 6%). One case of transient creatinine increase was reported as a severe adverse event, resolving without sequelae. Conclusions: Treatment with one cycle carboplatin AUC7 and 30-36 Gy involved-node radiotherapy for stage IIA/B seminoma is feasible and demonstrates a very favorable early toxicity profile. Clinical trial information: NCT01593241.

Treatment of refractory germ-cell tumours with single-agent cabazitaxel: a German Testicular Cancer Study Group case series.

Outcomes of multiply relapsed, refractory germ-cell tumour (GCT) patients remain poor with an overall survival (OS) of a few months only. Thus, new therapeutic advances are urgently needed. Cabazitaxel has shown preclinical activity in platinum-resistant GCT models. Here, we report the first clinical case series of cabazitaxel treatment for platinum-refractory GCT. Data of multiply relapsed GCT patients receiving single-agent cabazitaxel were retrospectively analysed. Endpoints included 12-week progression-free survival (PFS) rate, disease control rate, tumour marker responses, median PFS and OS, and toxicity. Cabazitaxel showed limited activity in 13 heavily pre-treated GCT patients. After a median follow-up of 23weeks (IQR 29), 69% of patients were deceased. A median of 2 cycles of cabazitaxel (range 1-7) were applied. The 12-week PFS rate was 31%. Median PFS and OS were 7 and 23weeks, respectively. Two patients achieved objective responses (15%), three patients (23%) achieved a tumour marker decline ≥ 50%, and the disease control rate was 39%. Cabazitaxel was well tolerated. CTCAE° III-IV haemato-toxicity was most common (54%), and dose reductions were scarce (15%). In this case series, cabazitaxel showed limited activity in heavily pre-treated GCT patients. Two-phase II studies are underway (NCT02115165, NCT02478502) prospectively assessing cabazitaxel in multiply relapsed GCTs.

Management of growing teratoma syndrome (GTS): Results of the German Testicular Cancer Study Group.

566 Background: Growing teratoma syndrome (GTS) is an infrequent clinical phenomenon constituting only about 2 to 8% of all testis cancer patients. Data in the literature on the therapy of GTS are sparse, reflecting the rarity of the disease. The objective of was to determine the diagnostic, surgical and oncological outcome of patients with GTS treated in the 21st century. Methods: Between 01/2000 and 01/2010 post-chemotherapeutic retroperitoneal lymph node dissections (PCRLND) were performed in 296 patients with advanced NSGCT. We analysed the peri- and postoperative outcome of 16 patients (5.4%) that fulfilled the criteria of a GTS: enlarging metastatic mass in the retroperitoneum or visceral organs during systemic chemotherapy with normalized or decreasing tumour markers. Results: Mean patient age was 31 years (17-57). Initially, all patients had NSGCT with a good or intermediate prognosis according to IGCCCG; one patient had a poor prognosis. In all cases the primary tumour predominantly contained mature teratoma; two patients had a clinical stage IIb, nine and three presented with clinical stage IIc and III respectively. Median tumour diameter at time of surgery was 8.1 cm (1.5-32). Tumour markers were plateauing or normalized in all patients. Tumour masses were localized in the retroperitoneum in 15 patients; one patient demonstrated a pulmonary mass. After a median follow-up of 4.2 years, 2 patients developed outfield recurrences; all but one patients are alive. Conclusions: GTS is a rare disease among patients with advanced NSGCT and necessitates complete surgical resection of the masses with curative intention. Surgery should be considered at time of progression to facilitate complete removal of the growing teratoma and be performed in tertiary referral centers only.

Thromboprophylaxis and the route of administration of chemotherapy in testicular cancer patients in German-speaking countries.

Due to the excellent cure rates for testicular cancer (TC), focus has shifted towards decreasing therapy-related morbidities. Thrombosis is a frequent complication of cisplatin chemotherapy. Furthermore, the optimal route of administration for chemotherapy is still under debate. The purpose of this study was to assess the patterns of care concerning dosing and duration of thromboprophylaxis currently utilized in TC patients in German-speaking countries as well as the route of chemotherapy administration. A standardized questionnaire was sent to all members of the German TC Study Group (GTCSG) and to all the urological university hospitals in Germany. The questionnaire was also sent to the oncologic clinics at those universities where urologists do not administer chemotherapy. The response rate was 87% (55/63). Prophylactic anticoagulation with low-molecular-weight heparin (LMWH) was administered in 94% of the clinics. The dosing of LMWH was prophylactic (85%), high prophylactic (adjusted to bodyweight) (7%), or risk adapted (9%). After completion of chemotherapy, anticoagulation was continued in 15 clinics (33%) for 2 to 24weeks, while the remainder stopped the LMWH upon cessation of chemotherapy. Chemotherapy was administered via central venous access in 59%, peripheral IV in 27%, or both in 14% of the clinics. Most of the institutions performed some form of thromboprophylaxis, although the modes of application varied by institution type and amongst the urologists and oncologists. Prospective studies are needed to evaluate the incidence, date of occurrence, and risk factors of venous thrombosis during TC chemotherapy to provide a recommendation concerning prophylactic anticoagulation.

Efficacy and safety of gemcitabine, oxaliplatin, and paclitaxel in cisplatin-refractory germ cell cancer in routine care—Registry data from an outcomes research project of the German Testicular Cancer Study Group

BackgroundChemotherapy (CTX) with gemcitabine, oxaliplatin, and paclitaxel (GOP) has demonstrated efficacy with an overall response rate (ORR) of approximately 50% in patients with multiply relapsed or cisplatin-refractory germ cell cancer (GCC) or both within a phase II study. We analyzed the efficacy and safety of GOP in routine clinical practice within a registry of the German Testicular Cancer Study Group. MethodsOverall, 63 patients with refractory GCC, who received GOP because of progression under cisplatin-based treatment or relapse after high-dose CTX, were included in this database. Patient characteristics, response rate, toxicity, progression-free and overall survival (OS) were analyzed. For further risk stratification, univariate and multivariate analyses were performed. ResultsGOP was applied as second to eighth treatment line (median fourth) after cisplatin-based CTX. The ORR was 44% with complete remissions achieved in 8 patients (4 patients with CTX plus additional residual tumor resections and 4 patients with CTX alone) and partial remissions achieved in 19 of all for best response evaluable patients. The median progression-free survival and OS were 4.0 months (95% CI: 3.08–4.94) and 13.3 months (95% CI: 9.50–17.06), respectively. Long-term OS of>2 years was achieved in 13 (21%), and grade III and IV toxicities, mainly thrombocytopenia and leukopenia, occurred in 29 patients. ConclusionOur results were similar compared with the previous results from the phase II study with a distinct activity with an ORR of 44%, and a long-term OS in 21% of the patients. Our data support the recommendation to use GOP ± secondary surgery in patients with multiply refractory metastatic GCC.

German second-opinion network for testicular cancer: sealing the leaky pipe between evidence and clinical practice.

In 2006, the German Testicular Cancer Study Group initiated an extensive evidence-based national second-opinion network to improve the care of testicular cancer patients. The primary aims were to reflect the current state of testicular cancer treatment in Germany and to analyze the project’s effect on the quality of care delivered to testicular cancer patients. A freely available internet-based platform was developed for the exchange of data between the urologists seeking advice and the 31 second-opinion givers. After providing all data relevant to the primary treatment decision, urologists received a second opinion on their therapy plan within <48 h. Endpoints were congruence between the first and second opinion, conformity of applied therapy with the corresponding recommendation and progression-free survival rate of the introduced patients. Significance was determined by two-sided Pearson’s χ2 test. A total of 1,284 second-opinion requests were submitted from November 2006 to October 2011, and 926 of these cases were eligible for further analysis. A discrepancy was found between first and second opinion in 39.5% of the cases. Discrepant second opinions led to less extensive treatment in 28.1% and to more extensive treatment in 15.6%. Patients treated within the framework of the second-opinion project had an overall 2-year progression-free survival rate of 90.4%. Approximately every 6th second opinion led to a relevant change in therapy. Despite the lack of financial incentives, data from every 8th testicular cancer patient in Germany were submitted to second-opinion centers. Second-opinion centers can help to improve the implementation of evidence into clinical practice.

First salvage treatment in patients with advanced germ cell cancer after cisplatin-based chemotherapy: analysis of a registry of the German Testicular Cancer Study Group (GTCSG)

We analyzed prognostic categories at first relapse according to the International Prognostic Factors Study Group (IPFSG) criteria as well as the efficacy of salvage treatment. 143 patients with relapsed or refractory germ cell cancer undergoing first salvage treatment with conventional-dose (CD-CX, n = 48) or high-dose chemotherapy with autologous stem cell support (HD-CX, n = 95) contributed by nine centers were retrospectively analyzed. Prognostic subgroups according to IPFSG criteria were: very low risk 13/143, low risk 36/143, intermediate risk 66/143, high risk 22/143, and very high risk 6/143 patients. The IPFSG categories significantly correlated with overall survival (OS) (p = 0.025) after 1st salvage treatment. After a median follow-up of 19 months, 55 % of all patients had relapsed and 33 % had died. For the entire cohort, progression-free survival (PFS) rate after 2 years was 43 %, and OS rate after 5 years was 52 %. Compared to the HD-CX group, vital carcinoma was found more often in secondarily resected lesions following CD-CX (22/29 vs. 22/45; p = 0.021). Second relapse rate was higher with 75 versus 44 %, resulting in a shorter median PFS with 8 versus 42 months (p < 0.001), but this did not translate into different OS (p = 0.931). At subsequent relapses, 26/36 patients received HD-CX as ≥2nd-salvage treatment. This analysis confirms the prognostic value of the IPFSG prognostic score. HD-CX seemed superior to CD-CX as first salvage treatment with respect to PFS in this retrospective analysis.

First-salvage treatment in patients with recurrent or refractory advanced germ-cell cancer after cisplatin-based chemotherapy: A database of the German Testicular Cancer Study Group.

4559 Background: About 20-30% of patients (pts) with advanced germ-cell cancer (GCC) relapse after cisplatin-based chemotherapy. This database evaluates first salvage treatment and the prognostic categories at first relapse according to the International Prognostic Factors Study Group (= IPFSG; JCO 2010). Methods: A total of 144 pts (78% nonseminoma) with relapsed or refractory GCC undergoing 1st salvage treatment with either conventional (CD-CX) or high-dose chemotherapy with autologous stem cell support (HD-CX) from 16 German centers were retrospectively analysed. Results: Subgroups according to the IPFSG prognostic categories, were: very low risk in 9/144 (6%), low risk in 26/144 (18%), intermediate risk in 78/144 (54%), high risk in 27/144 (19%), and very high risk in 4/144 pts (3%). 1st salvage treatment consisted of HD-CX in 96 (67%) and CD-CX in 48 pts (33%). Treatment response was CR/PR- in 60%, PR+/SD in 33%, and PD in 7%. After a median follow-up (mFU) of 21 months (mos) (range, 0 – 193), 53% of all pts had relapsed and 30% had died resulting in a median progression-free survival (PFS) of 7 mos (95%CI 0-16) and overall survival (OS) of 47 mos (95%CI 21-73). At subsequent relapses, 25/48 pts (52%) received HD-CX as &gt; 2nd-salvage treatment. For the total cohort, PFS rate after 2 years was 35%, and OS rate after 5 years was 53%. Stratification according to IPFSG prognostic categories significantly correlated with PFS (p=0.001) and OS (p=0.004) after 1st salvage treatment. Even among high-risk and very high risk (n=31, mFU 12 mos) a PFS of 37 % at 2 years and an OS of 60 % at 2 years was observed, after 1st or 2nd salvage treatment, which might be due to patient selection and short follow-up. Conclusions: IPFSG prognostic categories highly correlated with observed PFS and OS after first salvage treatment in this cohort of pts with refractory or relapsed GCC. First salvage treatment with CD- or HD-CX resulted in overall 5 year-OS rates of about 50% across all prognostic categories. Even pts with high and very high risk achieved 2 year-OS rates of about 60% with salvage HD-CX at first or subsequent relapses.

Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: A survey of the German Testicular Cancer Study Group

BackgroundThe treatment of testicular intraepithelial neoplasia (TIN), the progenitor of testicular germ cell tumours (GCTs), is based on little data. Patients and methodsTwo hundred and twenty-eight GCT patients with contralateral TIN were retrospectively enrolled. Ten had surveillance, 122 radiotherapy to testis with 18–20 Gy, 30 cisplatin-based chemotherapy (two cycles), 51 chemotherapy (three cycles), and 15 carboplatin. The study end point was a malignant event (ME), defined as detection of TIN upon control biopsy or occurrence of a second GCT. The Secondary end point was hypogonadism during follow-up. ResultsNumbers, proportions of ME, and median event-free survival (EFS) times were: radiotherapy N = 3, 2.5%, 11.08 years; chemotherapy (two cycles) N = 15, 50%, 3.0 years; chemotherapy (three cycles) N = 12, 23.5%, 9.83 years; carboplatin N = 10, 66%, 0.9 years; surveillance N = 5, 50%, 7.08 years. EFS is significantly different among the groups. Hypogonadism rates were in radiotherapy patients 30.8%, chemotherapy (two cycles) 13%, chemotherapy (three cycles) 17.8%, carboplatin 40%, surveillance 40%. ConclusionsLocal radiotherapy is highly efficacious in curing TIN. Chemotherapy is significantly less effective and the cure rates are dose-dependent. Though hypogonadism occurs in one-third of patients, radiotherapy with 20 Gy remains the standard management of TIN.

Residual Tumor Size and IGCCCG Risk Classification Predict Additional Vascular Procedures in Patients with Germ Cell Tumors and Residual Tumor Resection: A Multicenter Analysis of the German Testicular Cancer Study Group

Background Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome. Objectives The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients. Design, setting, and participants A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets. Measurements The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume. Results and limitations In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p = 0.0047) and residual tumor size (3.7% size <5 cm vs 17.9% size ≥5 cm; p < 0.0001). In multivariate analysis, IVC intervention was significantly associated with residual tumor size ≥5 cm (odds ratio [OR]: 4.61; p = 0.0007). In a predictive model combining residual tumor size and IGCCCG classification, every fifth patient (20.4%) with a residual tumor size ≥5 cm and intermediate or poor prognosis needed an IVC intervention during RTR. The need for an aortic prosthesis showed no correlation to either IGCCCG ( p = 0.1811) or tumor size ( p = 0.0651). Conclusions The necessity for IVC intervention during RTR is correlated to residual tumor size and initial IGCCCG classification. Patients with high-volume residual tumors and intermediate or poor risk features must initially be identified as high-risk patients for vascular procedures and therefore should be referred to specialized surgical centers with the ad hoc possibility of vascular interventions.

High-dose chemotherapy with autologous peripheral blood stem cell transplantation in patients with poor- and intermediate-prognosis metastatic germ cell tumors: A retrospective monocenter analysis of 44 cases.

e15043 Background: Metastatic germ cell tumors (GCT) are curable. The International Germ Cell Cancer Collaborative Group (IGCCCG) reports a poor prognosis subgroup with a 5-year survival rate of 48%. High-dose chemotherapy with autologous peripheral blood stem cell transplantation (HD-PBSCT) in these patients showed promising results in phase II trials, but failed to show significant advantage in randomized trials. We report on our series of patients with poor and intermediate prognosis GCT treated with individually tailored multiple-course HD-PBSCT and secondary surgery of remaining tissue. Methods: We performed a retrospective analysis of our complete single center series of 44 patients (40 poor prognosis; 4 intermediate prognosis) treated with HD-PBSCT. All patients received 1 up to 6 cycles of standard-dose cisplatin-etoposide-ifosfamide (PEI) chemotherapy followed by granulocyte colony-stimulating factor and stem cell mobilisation. Subsequent high-dose chemotherapy regimen HD-PEI was adapted from a phase I/II trial of the German Testicular Cancer Study Group (GTCSG). In 14 patients we added paclitaxel according to another phase I/II study by the GTCSG. Up to 4 cycles of HD-chemotherapy were administered according to individual patient’s response and tolerability. Patients with residual disease in computed tomography (CT) or positron-emission tomography (PET)-CT underwent secondary surgery. Results: In this retrospective analysis the CR rate after up to 4 cycles of HD-PBSCT and resection was 73%. Three patients showing a marker-negative PR did not undergo surgery, because they were PET negative and/or fine needle aspiration did not show viable tumor. The 3-year survival rate was 80%, with a median follow up of 43 months (range: 3-130 months). Disease-related death rate was 16%. Treatment-related death after HD-PBSCT did not occur. One patient died postoperatively. Conclusions: In our single center experience multiple courses of individually tailored HD-PBSCT is a safe and effective treatment option in poor and intermediate prognosis metastatic germ cell cancer.

832 PROGNOSTIC CLINICAL PARAMETERS TO PREDICT THE NECESSITY OF RECONSTRUCTIVE VASCULAR SURGERY FOR PATIENTS WHO UNDERGO POSTCHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR ADVANCED NONSEMINATOUS GERM CELL TUMORS (NSGCT). RESULTS OF THE GERMAN TESTICULAR CANCER STUDY GROUP (GTCSG) AND THE ASSOCIATION OF UROLOGIC ONCOLOGY (AUO)

You have accessJournal of UrologyPenis/Testis/Urethra: Benign & Malignant Disease1 Apr 2011832 PROGNOSTIC CLINICAL PARAMETERS TO PREDICT THE NECESSITY OF RECONSTRUCTIVE VASCULAR SURGERY FOR PATIENTS WHO UNDERGO POSTCHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR ADVANCED NONSEMINATOUS GERM CELL TUMORS (NSGCT). RESULTS OF THE GERMAN TESTICULAR CANCER STUDY GROUP (GTCSG) AND THE ASSOCIATION OF UROLOGIC ONCOLOGY (AUO) Axel Heidenreich, Klaus Peter Diekmann, Hans Schmelz, Christoph Winter, and David Pfister Axel HeidenreichAxel Heidenreich Aachen, Germany More articles by this author , Klaus Peter DiekmannKlaus Peter Diekmann Hamburg, Germany More articles by this author , Hans SchmelzHans Schmelz Koblenz, Germany More articles by this author , Christoph WinterChristoph Winter Düsseldorf, Germany More articles by this author , and David PfisterDavid Pfister Aachen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.652AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES PC-RPLND remains an integral part of the multimodality treatment for advanced NSGCT. The need to resect and to replace the major retroperitoneal vessels must be known preoperatively to enable complete resection of the residual masses. METHODS PC-RPLND was performed in 411 patients with NSGCT and normalized (81%) or plateauing (19%) tumor markers following 3–4 cycles PEB/PEI. PC-RPLND was performed in 5 institutions with a variable surgical frequency of 14 to 158 PC-RPLNDs. Good, intermediate, and poor prognosis according to the IGCCCG criteria was identified in in 59.8%, 21.2%, and 19% respectively. RESULTS Resection of the inferior vena cava was performed in 28 (6.81%) patients, resection of the abdominal aorta was necessary in 13 (3.16%) patients. In 29/41 (70.7%) adjunctive surgical procedures such as nephrectomy, small bowel resection, ureteral resection had to be performed to ensure complete resection of the residual masses. Histologically vital carcinoma or mature teratoma was identified in 78.1% of the resected vascular specimens. Mean time of surgery was 295 (243–615) Min., mean blood loss was 690 (350 – 3400) ml. Good prognosis was identified in 15.4%, an intermediate and poor prognosis was present in 41%and 43.6%, respectively. Of all 411 patients involvement of the major retroperitoneal vessels was found in 3.2%, 18.4% and 21.8% with good, intermediate, and poor prognosis, respectively. The mean tumor diameter was 5.9 (1.0 – 32) cm for the entire cohort and 9.8 (4–32) cm for the cohort of patients with vascular surgery. Significant prognosticators to predict vascular involvement were identified by multivariate analysis: intermediate/poor prognosis, number of cycles of chemotherapy, tumor diameter > 14cm, circumferential encasement of > 50% of the vessel diameter. CONCLUSIONS Complete resection of the inferior vena cava or the abdominal aorta during PC-RPLND is necessary in about 10% of patients. The identified predictors enable already preoperatively a risk adapted interdisciplinary approach for complete resection of the residual masses in an experienced centre. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e335 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Axel Heidenreich Aachen, Germany More articles by this author Klaus Peter Diekmann Hamburg, Germany More articles by this author Hans Schmelz Koblenz, Germany More articles by this author Christoph Winter Düsseldorf, Germany More articles by this author David Pfister Aachen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Partial Orchiectomy for Presumed Malignancy in Patients With a Solitary Testis Due to a Prior Germ Cell Tumor: A Large North American Experience

Partial orchiectomy is becoming more accepted for indications such as a metachronous germ cell tumor due to reported oncological control, and minimal functional, physical and psychological morbidity. Most data originate from Europe. Thus, we reviewed our North American experience with such men who underwent partial orchiectomy for a presumed contralateral testicular malignancy. We identified demographic, clinical, pathological and outcome data on men in our institutional database who underwent partial orchiectomy for presumed testicular malignancy from 1994 to 2009 and had a prior germ cell tumor. Patients were followed with examination, markers and imaging. We identified 27 men, of whom 17 (63%) had malignancy, including seminoma in 9, teratoma in 3, embryonal lesion in 1, Leydig cell tumor in 3 and carcinoma in situ in 1, and 10 (37%) had benign lesions. Frozen section was accurate, no positive margins were reported and all tumors were stage 1. Carcinoma in situ was found in 9 patients (53%). No perioperative complications were recorded. Management after partial orchiectomy was observation in 12 of 17 cases. Two patients underwent completion orchiectomy for local recurrence of carcinoma in situ only, including chemotherapy in 1. A patient with seminoma elected radiation and 1 required retroperitoneal lymph node dissection for teratoma. The remaining 5 patients with carcinoma in situ were surveilled. Of the men 31% required testosterone substitution. All patients were disease free at a median 5.7-year followup with no local recurrences. Partial orchiectomy is an option to decrease morbidity in men with a metachronous germ cell tumor. Clearly a definite benefit of partial orchiectomy is that a significant proportion of patients with suspicious testicular lesions did not have malignancy and were definitively treated with an organ sparing approach. However, partial orchiectomy is potentially associated with the need for adjuvant treatment and androgen substitution, which should be discussed with all patients.

Testosterone deficiency in testicular germ-cell cancer patients is not influenced by oncological treatment

The aim of the study was to investigate prospectively the prevalence of testosterone deficiency (TD) in patients with testicular germ-cell cancer (TGCC) using longitudinal data. A total of 376 TGCC patients were evaluated for serum testosterone levels before, during and after the following therapies: cisplatin-based polychemotherapy, carboplatin monotherapy, radiotherapy or surgery only. Complete serial hormone analyses were performed on 160 patients (age: 33.8±9.1years, mean±SD). All patients received treatment according to the guidelines of the 'German Testicular Cancer Study Group' and the 'European Germ Cell Cancer Consensus Group' or within studies performed by the 'European Organisation for Research and Treatment of Cancer' and the 'Deutsche Krebsgesellschaft'. Main outcome measurements were sexual hormone profiles over time. Statistical analysis of 1831 testosterone serum levels over time revealed a persistent TD in 23.9% of seminoma and 26.2% of non-seminoma patients. TD was associated with subnormal residual testicular volumes (<12mL). In conclusion, TD rates are high in testis cancer patients. This is present at primary diagnosis and most likely related to testicular dysgenesis or atrophy. Our longitudinal evaluation indicates that treatment modalities have minor influence and effect on the persistently high rates of TD in TGCC patients.

Burden or Relief: Do Second-Opinion Centers Influence the Quality of Care Delivered to Patients with Testicular Germ Cell Cancer?

BackgroundTo improve the quality of care, the German Testicular Cancer Study Group (GTCSG) has been publishing a series of testicular germ cell cancer guidelines since 1996. These guidelines were updated in the 2008 publication, “European Consensus on Diagnosis and Treatment of Germ Cell Cancer.” Several studies have shown that published guidelines have a limited effect on clinical practice. For this reason, the GTCSG made a further effort in 2006 to improve the quality of care by establishing a national second-opinion system for therapy planning for patients who underwent orchiectomy and staging evaluations. ObjectiveThe primary aim was to analyze the influence of the second-opinion system on guideline implementation with a view to improving the quality of care. Design, setting, and participantsAn Internet data exchange was established between the urologist seeking advice and the second-opinion centers. Second-opinion centers were 18 clinics that had contributed toward developing treatment guidelines. MeasurementsData sets included the primary clinical, radiologic, and pathohistologic data; the planned therapy; the therapy recommended by the second-opinion center; and the follow-up. Results and limitationsFrom February 2006 to September 2008, 642 second opinions were requested. The therapy planned by the urologist seeking advice differed from that recommended by the second-opinion center in 32.3% of the cases. The discrepancy was significantly higher for nonseminomas than for seminomas (p=0.045) and showed a tendency to increase with advancing tumor stage (p=0.067). In cases of discrepancy, the applied therapy coincided with the second opinion in 71.8% of the cases. A discrepant second opinion prevented overtreatment in 40.3% and undertreatment in 26.5%. ConclusionsApproximately every sixth second opinion resulted in a relevant change in the scope of therapy. Published guidelines for germ cell cancer are applied only sporadically and should be supported by second-opinion systems.

Testikuläre Keimzelltumoren

To improve quality of care, since 1989 the German Testicular Cancer Study Group (GTCSG) has published a series of guidelines on testicular germ cell cancer. These guidelines were updated in the 2007 publication"European Consensus on Diagnosis and Treatment of Germ Cell Cancer" (ECDTGCC). As an additional approach to improve the quality of care, the GTCSG established a national second-opinion system in 2006. The objective of this article is to summarise the present results, particularly regarding the interdependence between the guidelines and the second-opinion system.Data was exchanged between urologists and the second-opinion centres (SOCs) via the Internet. Data sets included the clinical primary data after orchiectomy, the intended therapy, the SOC's therapy recommendation, and the follow-up. The SOCs were 18 clinics that had qualified themselves through their participation in developing the ECDTGCC.From February 2006 to September 2008, 642 second opinions were requested. The discrepancy between the urologists' intended therapy and the SOCs' recommendations was 32.3%. The deviating second opinion in 40.3% (26.5%) of cases prevented overtreatment or undertreatment.Published guidelines are applied only sporadically. The results of the SOC system show that on the basis of this system, guidelines can be better implemented; in turn, the discrepancy between evidence-based guidelines and the actual treatment administered can be diminished.