International Germ Cell Cancer Collaborative Group Research Articles

High dose chemotherapy and autologous stem cell transplantation for salvage therapy of relapsed /refractory germ cell tumors; a single center experience.

The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1 to 3 plus etoposide 750 mg/m2 on days 1 to 3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment related complications and survival outcomes were recorded. The median age of the patients was 31 (range 18-62). The median follow-up was 31.1 months (95% CI, 28.9 to 33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1-43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium

AimsTo resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). Patients and methodsUsing the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. ResultsAmong 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). ConclusionTeratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

A population-based validation of the IGCCCG Update Consortium for survival in metastatic non-seminoma testis cancer.

In 2021, the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium reported improved overall survival (OS) rates in a modern cohort of metastatic non-seminoma testis cancer patients within each of the IGCCCG prognosis groups (96% in good vs. 89% in intermediate vs. 67% in poor), compared to the previous IGCCCG publication (92% in good vs. 80% in intermediate vs. 48% in poor). We hypothesized that a similar survival improvement may apply to a contemporary North-American population-based cohort of non-seminoma testis cancer patients. The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of IGCCCG prognosis groups on overall mortality (OM). Of 1672 surgically treated metastatic non-seminoma patients, 778 (47%) exhibited good vs. 251 (15%) intermediate vs. 643 (38%) poor prognosis. In the overall cohort, five-year OS rate was 94% for good prognosis vs. 87% for intermediate prognosis vs. 65% for poor prognosis. In multivariable Cox regression models predicting OM, intermediate (Hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.4-3.9, P<0.001) and poor prognosis group (HR 6.6, 95% CI 1.0-1.0, P<0.001) were independent predictors of higher OM, relative to good prognosis group. The survival improvement reported by the IGCCCG Update Consortium is also operational in non-seminoma testis cancer patients within the most contemporary SEER database. This observation indicates that the survival improvement is not only applicable to centres of excellence, but also applies to other institutions at large.

Clinico-epidemiological Profile and Outcome of Testicular Germ Cell Tumors: A Retrospective Study from a Tertiary Cancer Centre of North-East India

Introduction: Testicular Germ Cell Tumor (GCT) is a disease of young adults and is also highly curable. But in India, most of the patients present in an advanced stage and succumb to the disease as compared to the Western nations where patients present at an earlier stage and are mostly cured. Also, there is a scarcity of literature on testicular GCT from the Indian subcontinent. We present our experience from the Tata Memorial Centre of North-east India. Methods: This retrospective study was conducted at Tata Memorial Centre - BBCI, Guwahati for the period of 5 years from January 2018 to December 2022. The study focused on epidemiology, clinical presentation, and treatment outcomes. Results: Seventy-two cases of testicular GCTs were studied (28 cases were seminoma, and 44 were non-seminoma). Most common presenting stage was stage I in seminoma (53.6%), and stage III (77.2%) in non-seminoma. As per the International Germ Cell Cancer Collaborative Group (IGCCCG) classification, 25%, 35%, and 40% of patients were good-risk, intermediate-risk, and poor-risk in non-seminoma. In patients with seminoma, 54% and 46% were in good and intermediate-risk, respectively. Seventy-two percent and 21% had achieved a radiologic complete response (CR) and partial response (PR) with conventional chemotherapy in patients with seminoma. Radiologic CR and PR rates were 20% and 61% among non-seminoma patients. The median recurrence-free survival (RFS) was 43 months. RFS was better in seminoma versus non-seminoma, stage I versus stage III, and good-risk versus high-risk group. Conclusion: Most of our patients presented with an advanced stage of the disease and a high nodal burden. In patients with non-seminoma GCT, the best response to conventional chemotherapy was a partial response. The use of an alternative chemotherapy regimen to improve outcomes for such patients can be further explored.

Delivered relative dose intensity in adolescent and young adult germ cell tumours in England: Assessment of data quality and consistency from clinical trials compared to national cancer registration data.

Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens. However, evidence specific to AYA is limited by poor recruitment of AYA to trials and dose delivery outside trials not being well examined. We examined the utility of cancer registration data and a clinical trials dataset to investigate the delivery of relative dose intensity (RDI) in routine National Health Service practice in England, compared to within international clinical trials. Linked data from the Cancer Outcomes and Services Dataset (COSD) and the Systemic Anti-Cancer Therapy (SACT) dataset, and data from four international clinical trials were analysed. Survival over time was described using Kaplan-Meier estimation; overall, by age category, International Germ-Cell Cancer Collaborative Group (IGCCCG) classification, stage, tumour subtype, primary site, ethnicity and deprivation. Cox regression models were used to determine the fully adjusted effect of RDI on mortality risk. The quality of both datasets was critically evaluated and clinically enhanced. RDI was found to be well maintained in all datasets with higher RDIs associated with improved survival outcomes. Real-world data demonstrated several strengths, including population coverage and inclusion of sociodemographic variables and comorbidity. It is limited in GCT however, by the poor completion of data items enabling risk classification of patients and a higher proportion of missing data.

Patterns of Relapse in Australian Patients With Clinical Stage 1 Testicular Cancer: Utility of the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Surveillance Recommendations.

International guidelines advocate for active surveillance as the preferred treatment strategy for patients with stage 1 testicular cancer after orchidectomy although a personalized discussion is required. We conducted an analysis of individuals registered in iTestis, Australia's testicular cancer registry, to describe the patterns of relapse and outcomes of patients treated in Australia where the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Surveillance Recommendations are widely adopted. A total of 650 individuals diagnosed between 2000 and 2020 were included, 63% (411 of 650) seminoma and 37% (239 of 650) nonseminoma. The median age was 34 years (range 14-74). 26% (106 of 411) with seminoma and 15% (36 of 239) nonseminoma received adjuvant chemotherapy. After a median follow-up of 43 months (range 0-267) postorchidectomy, relapse occurred in 10% (43 of 411) of seminoma and 18% (43 of 239) of nonseminoma. The two-year relapse-free survival was 92% (95% CI, 89 to 95) and 82% (95% CI, 78 to 87) in seminoma and nonseminoma, respectively. All relapses (86 of 86) were detected at a routine surveillance visit; 98% (85 of 86) were asymptomatic and detected solely through imaging (62 of 86, 72%), tumor markers (6 of 86, 7%), or a combination (17 of 86, 20%). The most common relapse site was isolated retroperitoneal lymphadenopathy (53 of 86, 62%). No nonpulmonary visceral metastases occurred. At relapse, 98% (84 of 86) had International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis; 2 of 86 intermediate prognosis (both nonseminoma). No deaths occurred. In our cohort of stage 1 testicular cancer, where national surveillance recommendations have been widely adopted, recurrences were detected at routine surveillance visits and, almost exclusively, asymptomatic with IGCCCG good-prognosis disease. This provides reassurance that active surveillance is safe.

MP50-06 SURVIVAL OF TESTICULAR PURE TERATOMA VS. MIXED GERM CELL TUMOR PATIENTS ACROSS ALL STAGES

You have accessJournal of UrologyCME1 Apr 2023MP50-06 SURVIVAL OF TESTICULAR PURE TERATOMA VS. MIXED GERM CELL TUMOR PATIENTS ACROSS ALL STAGES Cristina Cano Garcia, Reha-Baris Incesu, Mattia Piccinelli, Stefano Tappero, Francesco Barletta, Zhe Tian, Fred Saad, Shahrokh F Shariat, Alberto Briganti, Alessandro Antonelli, Carlo Terrone, Ottavio De Cobelli, Markus Graefen, Derya Tilki, Mike Wenzel, Severine Banek, Luis A. Kluth, Felix K. H. Chun, and Pierre I. Karakiewicz Cristina Cano GarciaCristina Cano Garcia More articles by this author , Reha-Baris IncesuReha-Baris Incesu More articles by this author , Mattia PiccinelliMattia Piccinelli More articles by this author , Stefano TapperoStefano Tappero More articles by this author , Francesco BarlettaFrancesco Barletta More articles by this author , Zhe TianZhe Tian More articles by this author , Fred SaadFred Saad More articles by this author , Shahrokh F ShariatShahrokh F Shariat More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Alessandro AntonelliAlessandro Antonelli More articles by this author , Carlo TerroneCarlo Terrone More articles by this author , Ottavio De CobelliOttavio De Cobelli More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Derya TilkiDerya Tilki More articles by this author , Mike WenzelMike Wenzel More articles by this author , Severine BanekSeverine Banek More articles by this author , Luis A. KluthLuis A. Kluth More articles by this author , Felix K. H. ChunFelix K. H. Chun More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Treatment of testicular cancer is based on stage and the distinctions between seminoma and non-seminoma. However, within non-seminoma germ cell tumors (NSGCT) presence of potentially higher risk histological subtypes, such as presence of teratoma or even more so, presence of pure teratoma received limited consideration in treatment and follow-up guidelines based on the rarity of this histological subtype. Moreover, it is unknown to what extent the presence of pure teratoma increases the risk of mortality relative to mixed germ cell tumors (GCT) in metastatic, regional or localized stages. The aim of this study was to test for survival differences between testicular pure teratoma vs. mixed GCT patients within stages I, II and III. METHODS: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify testicular pure teratoma and mixed GCT patients. Kaplan-Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models tested for independent predictor status of pure teratoma vs. mixed GCT. RESULTS: Of 9183 patients, 433 (5%) had pure teratoma vs. 8750 (95%) mixed GCT. Median age was 28 years in both groups and median follow-up was 70 months. Pure teratoma differed from mixed GCT patients regarding higher clinical stage (stage III 27 vs. 19%), higher rate of retroperitoneal lymph node dissection (RPLND, 28 vs. 19%) and higher proportions of International Germ Cell Cancer Collaborative Group (IGCCCG) poor prognosis group (49 vs. 39%). Conversely, pure teratoma patients exhibited a lower rate of lung metastases than mixed GCT (21 vs. 43%; p<0.001). In stage I and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 92.3 vs. 97.2%, p<0.001; stage III: 66.8 vs. 77.8%; p=0.03), but not in stage II (96.3 vs. 95.9%). In stage I, survival differences originated from higher OCM in pure teratoma vs. mixed GCT (6.4 vs. 1.2%; p<0.001). Conversely in stage III, survival differences originated from higher CSM in pure teratoma vs. mixed GCT (29.4 vs. 19.0%; p=0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 3.97; p<0.01). Conversely, in stage III in multivariable CRR models pure teratoma was associated with higher CSM (HR: 1.71; p=0.01). CONCLUSIONS: In testicular pure teratoma, the survival disadvantage in stage I patients was previously unknown and relates to OCM. The survival disadvantage in stage III pure teratoma originates from higher CSM that was also previously unknown. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e687 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cristina Cano Garcia More articles by this author Reha-Baris Incesu More articles by this author Mattia Piccinelli More articles by this author Stefano Tappero More articles by this author Francesco Barletta More articles by this author Zhe Tian More articles by this author Fred Saad More articles by this author Shahrokh F Shariat More articles by this author Alberto Briganti More articles by this author Alessandro Antonelli More articles by this author Carlo Terrone More articles by this author Ottavio De Cobelli More articles by this author Markus Graefen More articles by this author Derya Tilki More articles by this author Mike Wenzel More articles by this author Severine Banek More articles by this author Luis A. Kluth More articles by this author Felix K. H. Chun More articles by this author Pierre I. Karakiewicz More articles by this author Expand All Advertisement PDF downloadLoading ...

EDEN (Etude Désescalade sEmiNome): Prospective therapeutic de-escalation and miRNA-M371 biomarker evaluation phase II study for stage IIa/IIb &lt; 3 cm seminomas.

TPS434 Background: At diagnosis, 10 to 15% of testicular pure seminomas have a stage II defined by the presence of retroperitoneal lymph node metastases. The optimal choice of treatment modalities are associated with excellent efficacy but also acute and late toxicities. De-escalating treatment for seminoma patients with stage IIb, IIc and III and good prognosis according to IGCCCG (International Germ Cell Cancer Collaborative Group) based on negative FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) after 2 cycles of EP (etoposide, cisplatine) chemotherapy seems feasible and safe according to SEMITEP cohort 2 results (Loriot Y, and al GETUG SEMITEP Trial: Eur Urol. 2022 Aug;82(2):172-179). Serum levels of microRNA (miR)-371a-3p (miRNA-M371) have been significantly associated with clinical stage and response to treatment in testicular germ cell tumors, with sensitivity and specificity higher than those of classic markers. The aim of the study NCT05529251 is to propose a new therapeutic approach for the stages IIa/IIb. Methods: This phase II, multicenter, prospective, randomized, non-comparative, de-escalation study will include patient with primary testicular seminomatous germ cell tumor with stage IIa/IIb &lt; 3 cm in largest diameter seminoma, histologically proved after orchiectomy and good prognosis according to IGCCCG and LDH (Lactate DesHydogenase) &lt; 2.5 x Upper Limit of Normal (ULN). They must have progressive disease and no prior treatment with radiotherapy or chemotherapy. In case of negative week-3 (after 1 EP cycle) PET-scan, patients will be randomized according to 2 arms ARM A: Boost of radiotherapy 20 to 30 Gray (Gy); ARM B Carboplatin AUC7 chemotherapy. In case of positive week-3 PET-scan: 3 courses of EP chemotherapy (ARM C). Primary outcome will include progression-free rate at 36 months. Secondary Outcome Measures will be serum level of miRNA M371, correlation with response to treatments and PET scan results, overall survival (OS), quality of life and tolerance to treatment. Blood samples (miRNA-M371) will be collected at screening, at the time of randomization before second cycle of chemotherapy or radiotherapy, at the end of treatment and at relapse. Enrollment has started in October 2022. A total of 90 patients will be included in the interventional study, leading to approximately 60 patients with negative FDG-PET randomized. Clinical trial information: NCT05529251 .

Predicting outcomes in female germ cell tumors using a modified International Germ Cell Cancer Collaborative Group classification system to guide management

ObjectiveWe previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and assessed it in female patients with germ cell tumors (GCTs). We sought to validate these modified IGCCCG (mIGCCCG) models in a new cohort. MethodsWe queried institutional databases for female patients with GCTs treated at Memorial Sloan Kettering Cancer Center from 1/1/1990–6/1/2020. The mIGCCCG model classifies patients with non-dysgerminomas as good, intermediate, or poor risk based on tumor markers using male IGCCCG cutoffs and absence/presence of non-pulmonary/peritoneal visceral metastasis. In dysgerminomas, good- and intermediate-risk groups are defined by absence/presence of non-pulmonary/peritoneal visceral metastasis. Progression-free survival (PFS) and overall survival (OS) were estimated for each group in the validation and combined original and validation cohorts. Associations between individual clinical factors and outcomes were evaluated. ResultsAmong 183 female patients with GCTs, clinical characteristics and outcomes were similar between the original (n = 93) and validation (n = 90) cohorts. In multivariable models, higher stage, older age, and non-dysgerminoma histology predicted worse PFS and OS (p < 0.05). Among 162 patients who received chemotherapy, preoperative and pre-chemotherapy mIGCCCG models were significantly associated with PFS and OS (p < 0.001 for all groups). With the preoperative model, 3-year PFS rates were 94%, 76%, and 50% in the good-, intermediate-, and poor-risk patients, respectively; OS rates were 96%, 86%, and 52%, respectively. Even within stage groups, mIGCCCG risk classifications were associated with clinical outcomes. ConclusionsA female-specific mIGCCCG risk model effectively stratifies patients and should be incorporated into clinical trials.

Predicting outcomes in female germ cell patients using a modified International Germ Cell Cancer Collaborative Group classification system to guide management (100)

<b>Objectives:</b> The International Germ-Cell Cancer Collaborative Group (IGCCCG) classification guides testicular germ-cell tumor (GCT) management, but there is no validated risk-based model for female patients (pts). We devised modified IGCCCG (mIGCCCG) classifications for female GCT pts undergoing chemotherapy, validated it in a separate cohort, and investigated clinical-pathologic factors associated with survival outcomes. <b>Methods:</b> An mIGCCCG risk classification was created in a test cohort of female GCT pts treated at a single center (1990-2012). In non-dysgerminomas, good, intermediate and poor-risk groups were stratified by tumor markers or metastatic site (AFP<1,000 ng/mL, HCG <5,000 mIU/mL or LDH<1.5x upper limit of normal (ULN); AFP 1,000-10,000 ng/mL, HCG 5,000-50,000 mIU/mL or LDH 1.5-10xULN; AFP>10,000 ng/mL, HCG>50,000 mIU/mL or LDH>10xULN OR non-pulmonary visceral [excluding peritoneal] metastases, respectively). In dysgerminomas, good and intermediate-risk groups were segregated by non-visceral metastases. The mIGCCCG risk model was validated in an independent cohort treated at the same institution (1986-2020). Progression-free survival (PFS) and overall survival (OS) were estimated among all pts using the Kaplan-Meier method. Differences by clinical-demographic factors were assessed with the log-rank test and Cox proportional-hazards models. <b>Results:</b> Median age, race, stage, histology, and chemotherapy regimen were similar between the original (<i>n</i>=93) and validation (<i>n</i>=94) cohorts. As in the original cohort, both preoperative and pre-chemotherapy mIGCCCG models were significantly associated with outcome in the validation and combined cohorts (Figure 1). Using pre-chemotherapy tumor markers, estimated 3-year OS rates for good, intermediate, and poor-risk pts were 89%, 92%, and 45%, respectively, in the original cohort, whereas 100%, 80%, and 50% in the validation cohort and 94%, 88%, and 51% in the combined cohort (all p-values <0.001). Using preoperative tumor markers, estimated 3-year OS rates for good, intermediate, and poor-risk pts were 92%, 86%, and 46%, respectively, in the original cohort, whereas 100%, 86%, and 60% in the validation cohort, and 96%, 86% and 54% in the combined cohort (all p-values <0.01). On multivariable regression analyses, worse PFS outcomes were associated with the higher stage (HR: 4.3, 95% CI: 1.5-12.0, p=0.006), non-dysgerminoma histology (HR: 3.4, 95% CI: 1.8-6.4, p<0.001), and older age (HR: 1.17 per 5-year increase, 95% CI: 1.03-1.32, p=0.01). Worse OS was also associated with the higher stage (HR: 3.7, 95% CI: 1.6-8.7, p=0.003), non-dysgerminoma histology (HR: 4.8, 95% CI: 1.1-20.0, p=0.04), and older age (HR: 1.28 per 5-year increase, 95% CI: 1.09-1.50, p=0.002). <b>Conclusions:</b> A female-specific mIGCCCG risk score identifies good-risk pts with better outcomes who may benefit from less intensive chemotherapy than intermediate- and poor-risk pts requiring more intensive chemotherapy and surveillance.Fig. 1

Management of stage II seminoma: a contemporary UK perspective.

Background and AimsTesticular Germ Cell Tumours (TGCTs) are the commonest young adult male cancer, with excellent survival outcomes even with metastatic disease. Chemotherapy, radiotherapy, and surgery are international guideline-dictated standard of care (SOC) treatments for International Germ Cell Cancer Collaborative Group (IGCCCG) “good risk” TGCT, but are associated with significant toxicities. Therapy de-escalation aims to reduce treatment morbidity whilst preserving cure rates, and has been adopted by some centres for stage IIA/B seminoma. Here, we report on the contemporary UK treatment landscape for stage IIA/B seminoma.MethodsA questionnaire-based survey of NHS England-designated specialist cancer centres hosting supra-regional specialist multi-disciplinary team (sMDT) services (n = 13) as well those within NHS Scotland, NHS Wales and Health and Social Care Northern Ireland. Respondents were asked to order preferences of SOC and therapy de-escalation treatments for stage IIA/B seminoma.ResultsWe identified significant geographical heterogeneity in treatment preferences. Whilst up to a third of centres have adopted a treatment de-escalation regimen, the majority deliver combination chemotherapy or radiotherapy.ConclusionA wider recognition of UK treatment heterogeneity and consideration of therapy de-escalation strategies at supra-regional sMDTs will increase stage IIA/B seminoma treatment options as part of clinical trials with oncological and quality of life endpoints.

Safety of Minimizing Intensity of Follow-up on Active Surveillance for Clinical Stage I Testicular Germ Cell Tumors

BackgroundWe have recommended active surveillance as the preferred management option for clinical stage I (CSI) testicular germ cell tumors (GCTs) since 1980. Over time, the recommended intensity of surveillance has decreased; however, the impact on relapse detection has not been investigated. ObjectiveTo examine relapse rate, time to relapse, extent of disease, and burden of treatment at relapse across decreasing surveillance intensity over time. Design, setting, and participantsCSI GCT patients under active surveillance from 1981 to 2021 were included in this study. Outcome measurements and statistical analysisThrough four major iterations in both nonseminomatous (NSGCT) and seminoma surveillance schedules, visit frequency, blood testing, and imaging have been decreased successively. Low-dose, noncontrast computed tomography (CT) scans were adopted in 2011. Categorical variables and time to relapse were compared using chi-square and Fisher’s exact or Kruskal-Wallis test, respectively. Results and limitationsA total of 1583 consecutive patients (942 with seminoma and 641 with NSGCT) were included. In seminoma, chest x-rays were reduced from 13 to one and CT scans were reduced from 20 to ten. Relapse rate, time to relapse, N or M category, and International Germ Cell Cancer Collaborative Group (IGCCCG) classification did not change. In NSGCT, chest x-rays were reduced from 27 to zero and CT scans were reduced from 11 to five. Relapse rate (from 46.2% to 21.2%, p = 0.002) and the median time to relapse (from 6.54 to 4.47 mo, p = 0.025) decreased. No difference in relapsed disease burden was identified by N, M, and S category or IGCCCG classification. Treatment burden at relapse and GCT cancer deaths remained similar for seminoma and NSGCT. Limitations include the retrospective design and large time period covered. ConclusionsDespite considerable reductions in surveillance intensity, we did not observe an increase in disease extent, treatment burden, or GCT cancer deaths upon relapse. These results support that our current lower-intensity active surveillance schedules are safe for managing CSI GCT. Patient summaryOur current reduced-intensity surveillance schedules for clinical stage I germ cell tumors appear to be safe.

High-dose chemotherapy for relapsed germ cell tumours: outcomes in low-volume specialized centres.

To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high-dose chemotherapy (HDCT) and autologous stem-cell transplantation in low-volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019. We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression-free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors. The median (range) age was 30 (14-68) years and GCT histology was non-seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional-dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC-paclitaxel (6%) and other (5%). With a median follow-up of 4.4 years, the 1-, 2- and 5-year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment-related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high-dose cycles received nor when HDCT was delivered after salvage CDCT. This large dual-national registry-based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low-volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice.

Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium.

PURPOSEThe classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990.MATERIALS AND METHODSData on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set.RESULTSCompared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update).CONCLUSIONThe IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium.

PURPOSEThe classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.MATERIALS AND METHODSData on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients.RESULTSCompared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH.CONCLUSIONPFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.

Outcome of testicular non-seminomatous germ cell tumours: report from a tertiary cancer centre in eastern India.

Non-seminomatous germ cell tumour (NSGCT) is a rare but highly curable malignancy. The literature on the management and outcomes of NSGCT is scarce from India. Here, we report the demography and treatment outcomes of NSGCT treated at our centre. This is a retrospective analysis of testicular and retroperitoneal NSGCT patients treated from March 2011 to December 2019. Patients were staged appropriately with imaging, pre- and post-operative tumour marker. Patients received stage adjusted adjuvant treatment after high inguinal orchiectomy. Patients with advanced disease were risk stratified as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. A total of 100 patients were treated with a median age of 28 years (Range: 18–51). Primary site was testis in 92 and retroperitoneum in 8 patients. Testicular violation was present in 17 (18%) patients. The stage of the disease was I in 32, II in 19 and III in 49 patients, respectively. IGCCCG risk groups were good in 29 (46%), intermediate in 13 (21%) and poor in 21 (33%) patients. Eleven patients (24%) underwent retroperitoneal lymph node dissection amongst 45 with post-chemotherapy residual disease. After a median follow-up of 26.6 months (range: 2.2–100.7), 3-year event-free survival and overall survival (OS) were 70.7% ± 5.6% and 78.2% ± 5.4%, respectively. S3 tumour marker (p = 0.01) and non-pulmonary visceral metastasis (p < 0.001) emerged as independent poor prognostic factors for OS in multivariate analysis. To conclude, testicular NSGCT has very high cure rate. Two-third patients present with advanced disease and one-third of them had poor risk disease. S3 tumour marker and non-pulmonary visceral metastasis are poor risk factors for OS.

Low Survival in Poor Prognosis Metastatic Germ Cell Cancer in Belarus.

PURPOSESince the development of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification in a 1997 study, high-income countries have reported a significant increase in survival for poor prognosis patients. There are scant data on IGCCCG risk-stratified survival from low- and middle-income countries. We assessed the progression-free survival (PFS) and overall survival (OS) rates in a contemporary cohort of Belarusian patients with advanced germ cell cancer (GCC) stratified by the IGCCCG prognostic classification and analyzed prognostic factors for survival.MATERIALS AND METHODSThe consecutive cohort of patients with clinical stage IIb-III testicular GCC or extragonadal germ cell tumors who received treatment or consultation in our two centers between 2010 and 2015 was included. All patients underwent primary chemotherapy. The patients were divided into seminoma and nonseminomatous germ cell carcinoma (NSGCC) subgroups. The Kaplan-Meier method was used to estimate 5-year PFS and OS.RESULTSThis study included 111 patients with a median age of 32 years, 95% of whom were diagnosed with testicular cancer. Seminoma and NSGCC were identified in 32 (29%) and 79 (71%) patients, respectively. The median follow-up was 6.1 years. The 5-year PFS and OS rates for the entire cohort were 70% and 77%, respectively. In patients with good prognosis seminoma and good, intermediate, and poor prognosis NSGCC, the estimated PFS rates were 76%, 88%, 74%, and 39% and those for OS were 83%, 97%, 83%, and 38%, respectively.CONCLUSIONIn our cohort of Belarusian patients with advanced germ cell tumors, we failed to demonstrate an improvement in PFS and OS compared with the 1997 IGCCCG study. Moreover, survival in poor prognosis group is inferior to that in IGCCCG and all contemporary series from high-income countries.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Metastatic Testicular Cancer.

We investigated the prognostic utility of pre-chemotherapy neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic germ cell tumors (GCTs) undergoing first-line chemotherapy. We utilized two institutional databases to analyze the pretreatment-derived NLR (dNLR). Predictive accuracy was evaluated using the Cox proportional hazard model adjusted for the international germ cell cancer collaborative group (IGCCCG) risk classification. Discriminatory accuracy was evaluated by determining the area under the receiver operating characteristic curve (AUROC). In total, 569 of 690 patients had available dNLR (IGCCCG: good, 64%; intermediate, 21%; poor, 16%). The 5-year and 10-year overall survivals (OSs) for good, intermediate, and poor risk groups were 96.2%, 92.8%, and 62.7% and 93.9%, 90.3%, and 62.7%, respectively. A dNLR of 2 provided the best discriminatory accuracy with an AUROC of 0.58 (95% CI: 0.52–0.65, p = 0.01) for progression-free survival (PFS), whereas for OS, a dNLR of 3 provided the best discriminatory accuracy with an AUROC of 0.62 (95% CI: 0.53–0.70, p < 0.01). A dNLR > 2 was associated with a hazard ratio (HR) of 1.99 (95% CI: 1.27–3.12, p < 0.01) for PFS, which lost its effect after adjustment for IGCCCG (HR: 1.44, 95% CI: 0.90–2.30, p = 0.13). For OS, a dNLR >3 was associated with an HR of 3.00 (95% CI: 1.79–5.01, p < 0.01), but lost its effect after adjustment for IGCCCG. Systemic inflammation plays a role in metastatic GCT, but its prognostic utility beyond established algorithms is limited. The general prognostic value of NLR can be seen across a number of tumors, although the consistency and magnitude of the effect differ according to cancer type, disease stage, and treatment received. We identified that an elevated NLR was associated with an adverse PFS and OS, but not independent of the IGCCCG risk classification. dNLRs >2 and >3 were associated with an adverse PFS and OS, respectively, in patients with metastatic GCT receiving first-line chemotherapy, but not independent of the IGCCCG risk classification.

Multimodality treatment outcome in patients with primary malignant mediastinal germ cell tumor in adults.

BackgroundMalignant mediastinal germ cell tumor (MGCT) is rare and has poor outcomes even after multimodality treatment. Data from resource‐poor countries are scarce in the literature.AimsTo evaluate the clinicopathologic features and treatment outcome of primary malignant MGCT at our center.Methods and ResultsSingle institutional data review of patients aged ≥18 years, treated with a diagnosis of malignant MGCT between Nov'2013 and Nov'2019. Risk stratification was done as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients were treated with platinum based chemotherapy and surgical resection for the residual disease was performed in non‐seminomatous histology.28 patients had MGCT with a median age of 25 years (range:18‐36) and all were male. Seven patients had superior vena cava obstruction (SVCO) at diagnosis and pre‐treatment histological diagnosis was available in 23 (82%) patients. Seven (25%) patients had seminoma histology, all were of good risk as per IGCCCG risk criteria, whereas others had non‐seminoma histology with poor‐risk group. Seven patients with seminoma histology achieved a complete response after initial treatment. Six patients with non‐seminoma histology underwent complete resection of residual disease post‐chemotherapy and five revealed residual viable tumors. After a median follow‐up of 10.8 months (range:2.9‐75), 3‐year progression‐free survival (PFS) and overall survival (OS) estimate was 61.2% and 94.7% in the whole cohort, respectively and 3‐year PFS and OS estimate was 100% in patients with seminoma histology.ConclusionsThis is the largest data set of MGCT patients' outcomes reported from India with multi‐modality treatment. All patients were male and one‐fourth had SVCO at presentation. Seminoma histology patients had a 100% outcome after initial platinum based chemotherapy. But, those with non‐seminoma histology had a poor outcome even with chemotherapy and surgery.

Improved outcomes in metastatic germ cell cancer: results from a large cohort study

PurposeTreatment of metastatic germ cell cancer (GCC) is based on the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic classification published in 1997. 5-year survival rates were reported to be 91%, 79%, and 48% for patients with good, intermediate and poor prognosis, respectively. However, treatment results may have improved over time due to cumulative experience, improved supportive care and modern-type chemotherapy.MethodsPatients with metastatic GCC who received cisplatin-based chemotherapy at two institutions in Munich between 2000 and 2013 were retrospectively studied. Clinical characteristics, treatment and outcomes were analyzed with respect to the IGCCG prognostic classification.ResultsOf 225 patients (median age 35 years), 72 (32%) had seminoma (S) and 153 (68%) nonseminoma. 175 (78%), 30 (13%) and 20 patients (9%) had good, intermediate and poor prognosis according to the IGCCCG classification. The 2-year-progression free survival of patients with good, intermediate and poor prognosis was 91%, 83% and 37%, and the 5-year-overall survival (OS) was 98%, 96%, and 66%, respectively. There was no significant difference in the OS between patients in the good and intermediate prognosis group.ConclusionCompared to data from the original IGCCCG classification system, the outcome of patients with metastatic GCC has considerably improved over time. While the prognosis of intermediate-risk patients is excellent, treatment in the poor-prognosis group remains to be improved.