Incremental dose-response effect of age on mortality in non-seminoma testis cancer patients

Author:

Incesu Reha-Baris1ORCID,Piccinelli Mattia Luca2,Morra Simone2,Scheipner Lukas2,Tappero Stefano2,Barletta Francesco2,Garcia Cristina Cano2,Tian Zhe2,Saad Fred2,Shariat Shahrokh F.3,Chun Felix K. H.4,Briganti Alberto5,Terrone Carlo6,Ahyai Sascha7,Longo Nicola8,de Cobelli Ottavio9,Tilki Derya10,Graefen Markus10,Karakiewicz Pierre I.2

Affiliation:

1. Centre Hospitalier de l'Université de Montréal Centre de Recherche

2. CHUM Research Centre: Centre de Recherche du Centre Hospitalier de l'Universite de Montreal

3. Medical University of Vienna: Medizinische Universitat Wien

4. Goethe University Frankfurt: Goethe-Universitat Frankfurt am Main

5. Università Vita Salute San Raffaele: Universita Vita Salute San Raffaele

6. University of Genoa: Universita degli Studi di Genova

7. Medical University of Graz: Medizinische Universitat Graz

8. Federico II University Hospital: Azienda Ospedaliera Universitaria Federico II

9. European Institute of Oncology: Istituto Europeo di Oncologia

10. Universitätsklinikum Hamburg-Eppendorf: Universitatsklinikum Hamburg-Eppendorf

Abstract

Abstract Background Age ≥ 40 predisposes to higher testis cancer-specific mortality (CSM) in non-seminoma. However, it is unknown, whether an incremental dose-response effect applies to subgroups of testis cancer patients (tertiles aged ≥ 40). We tested this hypothesis in contemporary non-seminoma patients. Methods The Surveillance, Epidemiology, and End Results (SEER) database (2004 − 2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of age on CSM after stratification for stage (I vs. II vs. III). Results Of 13,679 non-seminoma patients, 11,034 (81%) were aged < 40 vs. 2,645 (19%) were aged ≥ 40. Of patients aged ≥ 40, 943 were aged 40–44 (young age tertile) vs. 855 were aged 45–52 (intermediate age tertile) vs. 847 were aged ≥ 53 (old age tertile). In overall multivariable analyses relative to patients aged < 40, young age tertile (HR 1.4, p < 0.01), intermediate age tertile (HR 1.9, p < 0.001) and old age tertile (HR 3.6, p < 0.001) were associated with higher CSM. In stage-specific multivariable analyses relative to patients aged < 40, old age tertile predicted higher CSM in stage I (HR 4.7, p < 0.001), stage II (HR 9.9, p < 0.001) and stage III (HR 3.0, p < 0.001). In stage III, intermediate age tertile (HR 1.9, p < 0.001) and young age tertile (HR 1.5, p = 0.007) also predicted higher CSM. Conclusions We identified a dose-response effect of increasing age in non-seminoma patients aged ≥ 40, in the overall analysis as well as in stage-specific analyses.

Publisher

Research Square Platform LLC

Reference6 articles.

1. Adverse Prognostic Factors for Testicular Cancer-Specific Survival: A Population-Based Study of 27,948 Patients;Fosså SD;J Clin Oncol,2011

2. Howlader N, Noone AM, Krapcho M et al SEER Cancer Statistics Review, 1975–2018, National Cancer Institute. https://seer.cancer.gov/csr/1975_2018/

3. R Core Team (2022) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/

4. Changes in epidemiologic features of testicular germ cell cancer: Age at diagnosis and relative frequency of seminoma are constantly and significantly increasing;Ruf CG;Urologic Oncology: Seminars and Original Investigations,2014

5. Trends in Age and Histology of Testicular Cancer from 1980–2019: A Single-Center Study;Yamashita S;Tohoku J Exp Med,2020

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