OBJECTIVE: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT).
METHODS: Using 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.
RESULTS: Among 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).
CONCLUSIONS: Teratoma 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.

BACKGROUND: Historic evidence suggests that non-Caucasian race/ethnicity predisposes to higher testis cancer-specific mortality (CSM) in non-seminoma. However, it is unknown, whether higher CSM in non-Caucasians applies to Hispanics or Asians or African-Americans, or all of the above groups. In contemporary patients, we tested whether CSM is higher in these select non-Caucasian groups than in Caucasians, in overall and in stage-specific comparisons: stage I vs. stage II vs. stage III.
METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2004 -2019) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of race/ethnicity on CSM after stratification for stage (I vs. II vs. III) and adjustment for prognosis groups in stage III.
RESULTS: In all 13,515 non-seminoma patients, CSM in non-Caucasians was invariably higher than in Caucasians. In stage-specific analyses, race/ethnicity represented an independent predictor of CSM in Hispanics in stage I (HR 1.8, p = 0.004), stage II (HR 2.2, p = 0.007) and stage III (HR 1.4, p < 0.001); in African-Americans in stage I (HR 3.2; p = 0.007) and stage III (HR 1.5; p = 0.042); and in Asians in only stage III (HR 1.6, p = 0.01).
CONCLUSIONS: In general, CSM is higher in non-Caucasian non-seminoma patients. However, the CSM increase differs according to non-Caucasian race/ethnicity groups. Specifically, higher CSM applies to all stages of non-seminoma in Hispanics, to stages I and III in African-Americans and only to stage III in Asians. These differences are important for individual patient management, as well as for design of prospective trials.

BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.

Metastatic germ cell tumors of the testis (GCTs) are risk-stratified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system. This risk classification is based on anatomical risk factors as well as tumor marker levels of AFP, HCG, and LDH assessed pre-chemotherapy after orchiectomy treatment. An incorrect classification is possible when pre-orchiectomy marker levels are used, possibly resulting in over- or undertreatment of patients. The aim was to investigate the potential frequency and clinical relevance of incorrect risk stratification using pre-orchiectomy tumor marker levels.
A multicenter registry analysis, including patients with metastasized nonseminomatous GCT (NSGCT), was conducted by investigators of the German Testicular Cancer Study Group (GTCSG). Based on the marker levels at different timepoints, IGCCCG risk groups were calculated. The agreement was tested using Cohen\'s kappa.
A total of 672 of 1910 (35%) patients were diagnosed with metastatic NSGCTs, and 523 (78%) had sufficient data for 224 follow-up data points. By using pre-orchiectomy tumor marker levels, 106 patients (20%) would have been incorrectly classified. Seventy-two patients (14%) were classified into a higher risk category, and 34 patients (7%) were classified into a lower risk category. Cohen\'s kappa was 0.69 (p < 0.001), showing a strong agreement between the use of both marker timepoints. The treatment of misclassified patients would have resulted in an overtreatment of 72 patients or undertreatment of 34 patients.
The use of pre-orchiectomy tumor marker levels may lead to an incorrect risk classification and might subsequently lead to under- or overtreatment of patients.

BACKGROUND: The prognostic classification system of the International Germ Cell Cancer Cooperative Group (IGCCCG) for testicular germ cell tumors is based on the histological subtype, location of the primary tumor, extent of metastatic spread and prechemotherapy tumor marker serum concentrations.
OBJECTIVE: In this study, we aim to identify whether the use of preorchiectomy instead of prechemotherapy tumor marker serum concentration has an impact on IGCCCG risk group assignment.
METHODS: We performed a retrospective analysis including 135 patients with metastasized testicular germ cell tumors. Analysis of the clinical information with a focus on the tumor marker serum concentration preorchiectomy and prechemotherapy was performed, thus leading to the grouping of patients according to IGCCCG risk group assignment.
RESULTS: Using preorchiectomy instead of prechemotherapy tumor markers led to an incorrect IGCCCG risk group classification in 8% (11/135) of all patients, and consequently to a non-guideline concordant treatment. Up-staging was observed in 8 of 11 patients, representing 6% (8/135) of the total patient cohort. Three of the 11 misclassified patients showed a down-staging and thus describe 2% (3/135) of the total patient cohort.
CONCLUSIONS: Using preorchiectomy tumor markers instead of prechemotherapy serum concentration might lead to an incorrect IGCCCG risk group assignment as well as non-guideline concordant treatment. Consequently, prechemotherapy tumor marker serum concentration should be applied for guideline concordant staging of patients.
UNASSIGNED: HINTERGRUND: Das Klassifikationssystem zur Prognoseeinschätzung der International Germ Cell Cancer Cooperative Group (IGCCCG) für testikuläre Keimzelltumoren basiert auf dem histologischen Subtyp, der Lokalisation des Primärtumors und der Metastasen sowie der Serumkonzentrationen der Tumormarker vor Chemotherapie.
UNASSIGNED: Ziel der Arbeit war die Evaluation des Einflusses der Verwendung der Tumormarkerserumkonzentrationen vor Ablatio testis im Vergleich zu denen vor Chemotherapie im Hinblick auf die Eingruppierung entsprechend der IGCCCG-Klassifikation.
UNASSIGNED: Wir führen eine retrospektive Datenanalyse an 135 Patienten mit metastasiertem testikulärem Keimzelltumor durch, die eine Primärtherapie mit einer Chemotherapie erhalten haben. Es erfolgte die Analyse von klinischen Parametern mit Fokus auf der Tumormarkerserumkonzentration vor Ablatio testis und vor Chemotherapie, die zur Eingruppierung in eine Prognosegruppe entsprechend der IGCCCG-Klassifikation führten.
UNASSIGNED: Die Verwendung der Tumormarkerserumkonzentrationen zur Berechnung der IGCCCG-Klassifikation vor der Ablatio testis im Vergleich zu denen vor Chemotherapie führte bei 8 % (11/135) aller Patienten zu einer veränderten Prognosegruppe sowie daraus folgend nicht-leitliniengerechten Therapieschemata. Es zeigt sich ein „up-staging“ bei 8 der 11 Patienten und somit 6 % (8/135) der gesamten Patientenkohorte, d. h. die Serumkonzentrationen der Tumormarker sind nach Ablatio bis zum Beginn der Chemotherapie abgefallen. Bei 3 der 11 Patienten bzw. 2 % (3/135) der gesamten Patientenkohorte, kam es zu einem „down-staging“, d. h. die Tumormarker sind bis zum Beginn der Chemotherapie angestiegen.
UNASSIGNED: Die Verwendung der Tumormarkerserumkonzentrationen vor Ablatio testis im Vergleich zu denen vor Chemotherapie kann zu einer signifikanten IGCCCG-Fehlklassifikation und somit inkorrekter Therapie führen. Für ein leitlinienkonformes „staging“ der Patienten sollten folglich die Tumormarker vor der Chemotherapie verwendet werden.

BACKGROUND: Testicular cancer is one of the few solid cancers that can be cured even when it is metastasized with overall survival rate of more than 90%. The aim of this study was to establish the age adjusted incidence of testicular cancer and to critically assess the management of testicular tumor.
METHODS: This is a quantitative retrospective study utilizing a review of clinical notes for patients who underwent testicular orchidectomy. The number of cancer cases, types of pathology and cancer staging were examined.
RESULTS: There is no substantial difference between the crude and the age-standardized incidence, moreover no difference from the reported crude incidence by the Scottish intercollegiate guidelines. We found 55.1% of seminoma, 14.28% of non-seminoma and 30.61% of combined (seminoma and non-seminoma), and stage I disease in 61.22% of cases, stage II in 36.73% of cases, and stage IV in 2.04% of cases. Most of the cancers were in the age group 20 - 50 with the majority (48.97%) in the age group 31 - 40. About 42.85% of cases were identified with high tumor markers; higher percentage of seminoma at stage II (40.74%).
CONCLUSIONS: There is no substantial difference between the crude and the age-standardized incidence, moreover no difference from the reported crude incidence. Most of the cancers were in the age group 20 - 50 with the majority (48.97%) in the age group 31 - 40. Only 25% of seminomas had elevated tumor markers. Moreover, it is important to re-enforce strict adaptation to the IGCCCG prognostic factor-based classifications.

OBJECTIVE: Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer.
METHODS: Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome.
RESULTS: Of 93 patients, 92 (99%) underwent primary surgery and 85 (92%) received chemotherapy. Modified IGCCCG classification was significantly associated with progression-free survival (PFS) and overall survival (OS), both when applied preoperatively and pre-chemotherapy (p<0.001 for all four analyses). Progression after initial chemotherapy (n=29) was detected by imaging in 14 (48%) patients, by serum tumor markers in 6 (21%) patients, and by multiple methods in the rest. Seven (29%) of 24 patients treated with salvage chemotherapy achieved long-term PFS, including 4/6 who received high-dose chemotherapy (HDCT) as initial salvage versus 3/16 treated with other initial salvage regimens. The estimated 3-year OS rate was 84% (95% CI, 76-92%), with a trend favoring dysgerminoma over non-dysgerminoma histologies (p=0.12).
CONCLUSIONS: Modified IGCCCG classification was prognostic for female GCT patients in this cohort and identified a poor-risk group who may benefit from more intensive first-line chemotherapy. Both imaging and tumor marker evaluation were important in identifying relapses after first-line chemotherapy. The majority of long-term remissions with salvage therapy were achieved with initial salvage HDCT.