Age as a Predictor of Treatment Outcome in Metastatic Testicular Germ Cell Tumors

Terbuch, Angelika; Posch, Florian; Bauernhofer, Thomas; Pichler, Martin; Peinsith, Heidi; Szkandera, Joanna; Riedl, Jakob M.; Hutterer, Georg C.; Pummer, Karl; Partl, Richard; Kapp, Karin S.; Stöger, Herbert; Stotz, Michael; Gerger, Armin

doi:10.21873/anticanres.13753

Cited by 8 publications

(11 citation statements)

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“…The proper management include the risk-stratification with regard to thromboembolism, cardiovascular toxicity and neutropenic complications [4][5][6]. Even elderly patients with metastatic TGCT can achieve high cure rates similar to younger patients if they tolerate risk-adapted chemotherapy [7].…”

Section: Introductionmentioning

confidence: 99%

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Regouc

Belge

Lorch

et al. 2020

Cancers

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Testicular cancer is an important disease with increasing incidence and a high burden of morbidity and mortality in young men worldwide. Histological examination of the testicular tissue after orchiectomy plays an important role alongside patient history, imaging, clinical presentation and laboratory parameters. Surgical procedures and chemotherapeutic treatment provide a high chance of cure in early stages, though some patients in advanced stages belonging to a poor risk group experience cancer-related death. Though conventional serum-based tumor markers, including α-fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), are useful as prognostic and diagnostic biomarkers, unfortunately, these tumor markers only have a sensitivity of about 60%, and in pure seminoma even lower with about 20%. Therefore, the development of new tumor markers is an important and intensively ongoing issue. The analysis of epigenetic modification and non-coding RNA microRNAs (miRNAs) are carrying most promising potential as tumor markers in future. miRNAs are small RNAs secreted by testicular tumor cells and circulate and be measurable in body fluids. In recent years, miRNAs of the miR-371-373 cluster in particular have been identified as potentially superior tumor markers in testicular cancer patients. Studies showed that miR-371a-3p and miR-302/367 expression significantly differ between testicular tumors and healthy testicular tissue. Several studies including high prospective multi-center trials clearly demonstrated that these miRNAs significantly exceed the sensitivity and specificity of conventional tumor markers and may help to facilitate the diagnosis, follow-up, and early detection of recurrences in testicular cancer patients. In addition, other miRNAs such as miR-223-3p, miR-449, miR-383, miR-514a-3p, miR-199a-3p, and miR-214 will be discussed in this review. However, further studies are needed to identify the value of these novel markers in additional clinical scenarios, including the monitoring in active surveillance or after adjuvant chemotherapy, but also to show the limitations of these tumor markers. The aim of this review is to give an overview on the current knowledge regarding the relevance of non-coding miRNAs as biomarkers in testicular cancer.

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Section: Introductionmentioning

confidence: 99%

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Regouc

Belge

Lorch

et al. 2020

Cancers

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“…However, Terbuch et al found among metastatic TGCT cases that although higher age is associated with worse OS, it is not correlated with worse DFS or higher disease progression risk. Elderly patients could also gain high cure rates as younger patients if they tolerate riskadapted chemotherapy; thus, age might not remarkably affect the prognosis of metastatic TGCT cases (Terbuch et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

RNA-Binding Proteins Play an Important Role in the Prognosis of Patients With Testicular Germ Cell Tumor

Yao

Cong

et al. 2021

Front. Genet.

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Testicular germ cell tumors (TGCTs) are common urological neoplasms in young adult males. The outcome of TGCT depends on pathologic type and tumor stage. RNA-binding proteins (RBPs) influence numerous cancers via post-transcriptional regulation. The prognostic importance of RBPs in TGCT has not been fully investigated. In this study, we set up a prognostic risk model of TGCT using six significantly differentially expressed RBPs, namely, TRMT61A, POLR2J, DIS3L2, IFIH1, IGHMBP2, and NPM2. The expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression datasets. We observed by performing least absolute shrinkage and selection operator (LASSO) regression analyses that in the training cohort, the expression of six RBPs was correlated with disease-free survival in patients with TGCT. We assessed the specificity and sensitivity of 1-, 3-, 5-, and 10-year survival status prediction using receiver operating characteristic curve analysis and successfully validated using the test cohorts, the entire TCGA cohort, and Gene Expression Omnibus (GEO) datasets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses were carried out to seek the possible signaling pathways related with risk score. We also examined the association between the model based on six RBPs and different clinical characteristics. A nomogram was established for TGCT recurrence prediction. Consensus clustering analysis was carried out to identify the clusters of TGCT with different clinical outcomes. Ultimately, external validations of the six-gene risk score were performed by using the GSE3218 and GSE10783 datasets downloaded from the GEO database. In general, our study constructed a prognostic model based on six RBPs, which could serve as independent risk factor in TGCT, especially in seminoma, and might have brilliant clinical application value.

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“…The association was most evident in patients with metastatic disease (seminoma: HR 8.62; P < .001; nonseminoma: HR, 6.35; P < .001). 22 In a singleinstitution study of 1225 GCT patients, Terbuch et al 23 reported that higher age did not predict increased risk of progression; 5-year PFS was 85% in the <40years-of-age group and 83% in the ≥40years-of-age group. However, although not statistically significant, patients ≥40 years of age had numerically worse OS.…”

Section: Discussionmentioning

confidence: 99%

Survival outcomes and toxicity in patients 40 years old or older with relapsed metastatic germ cell tumors treated with high‐dose chemotherapy and peripheral blood stem cell transplantation

Agrawal

Abonour

Zaid

et al. 2021

Cancer

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BACKGROUND: High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective salvage therapy for relapsed metastatic germ cell tumors (GCTs) but has potential toxicity. Historically, an age of ≥40 years has been associated with greater toxicity and worse outcomes. METHODS: This is a retrospective analysis of 445 consecutive patients with relapsed GCT treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen. Kaplan-Meier methods and log-rank tests were used for progression-free survival (PFS) and overall survival (OS) analysis. RESULTS: A total of 329 patients were <40 years of age, whereas 116 patients were ≥40 years of age; HDCT was used as second-line therapy in 85% and 79%, respectively. Median follow-up time was 42.5 months (range, 0.3-173.4 months). Grade ≥3 toxicities were similar between either group, except for greater pulmonary (P = .02) and renal toxicity (P = .01) in the ≥40-years-of-age group. Treatment-related mortality was similar between both age groups: 10 patients (3%) in the <40-years-of-age group and 4 patients (3.5%) in ≥40-years-of-age group died from complications of HDCT. Two-year PFS for <40 years of age versus ≥40 years of age was 58.7% versus 59.6% (P = .76) and 2-year OS was 63.9% versus 61.5% (P = .93). Factors predicting worse PFS included Eastern Cooperative Oncology Group performance status ≥1, platinum refractory disease, nonseminoma histology, and not completing 2 cycles of HDCT. Age was not an independent predictor of worse outcomes. CONCLUSIONS: HDCT plus PBSCT is effective salvage therapy in patients ≥40 years of age with relapsed metastatic GCT. Patients ≥40 years of age experience similar rates of toxicity and treatment-related mortality as those <40 years of age.

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Age as a Predictor of Treatment Outcome in Metastatic Testicular Germ Cell Tumors

Cited by 8 publications

References 0 publications

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

RNA-Binding Proteins Play an Important Role in the Prognosis of Patients With Testicular Germ Cell Tumor

Survival outcomes and toxicity in patients 40 years old or older with relapsed metastatic germ cell tumors treated with high‐dose chemotherapy and peripheral blood stem cell transplantation

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