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Cited by 88Multiple and Secondary Primary CancersTesticular diseases and treatmentsChildhood Cancer Survivors' Quality of Life

Risk of Solid Cancer after Treatment of Testicular Germ Cell Cancer in the Platinum Era

Open access
Groot, Harmke J., Lubberts, Sjoukje, de Wit, Ronald, Witjes, Johannes A., Kerst, Jan Martijn, de Jong, Igle J., Groenewegen, Gerard, van den Eertwegh, Alfons J.M. +14 more·2018·Journal of Clinical Oncology
DOI 10.1200/jco.2017.77.4174
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Abstract

Purpose: Testicular cancer (TC) treatment increases risk of subsequent malignant neoplasms (SMNs). It is unknown whether changes in TC treatment over time have affected SMN risk. Methods: Solid SMN risk was evaluated in a multicenter cohort comprising 5,848 1-year survivors treated for TC before age 50 years between 1976 and 2007. SMN incidence was compared with cancer incidence in the general population. Treatment-specific risks were assessed using multivariable regression in a case-cohort design. Results: After a median follow-up of 14.1 years, 350 solid SMNs were observed, translating into a 1.8-fold (95% CI, 1.6-2.0) increased risk compared with general population rates. Solid SMN risk was increased in patients with seminoma and those with nonseminoma (standardized incidence ratio, 1.52 and 2.21, respectively). Patients with nonseminoma experienced increased risk of SMNs of the thyroid, lung, stomach, pancreas, colon, and bladder and of melanoma and soft tissue sarcoma, whereas those with seminoma experienced increased risk of SMNs of the small intestine, pancreas, and urinary bladder. The 25-year cumulative incidence of solid SMNs was 10.3% (95% CI, 9.0% to 11.6%). In multivariable analysis, platinum-based chemotherapy was associated with increased risk of a solid SMN (hazard ratio [HR], 2.40; 95% CI, 1.58 to 3.62), colorectal SMN (HR, 3.85; 95% CI, 1.67 to 8.92), and noncolorectal GI SMN (HR, 5.00; 95% CI, 2.28 to 10.95). Receipt of platinum 400 to 499 and ≥ 500 mg/m 2 increased solid SMN risk compared with surgery only (HR, 2.43; 95% CI, 1.40 to 4.23 and HR, 2.42; 95% CI, 1.50 to 3.90, respectively), whereas risk was not significantly increased with lower doses (HR, 1.75; 95% CI, 0.90 to 3.43). The HR of a GI SMN increased by 53% (95% CI, 26% to 80%) per 100 mg/m 2 of platinum-containing chemotherapy. The HR of an infradiaphragmatic SMN increased by 8% per Gray of radiation dose administered (95% CI, 6% to 9%; P < .001). Conclusion: Radiotherapy and platinum-containing chemotherapy are associated with increased solid SMN risk, specifically with GI SMNs.

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Authors
Groot, H. J., Lubberts, S., de Wit, R., Witjes, J. A., Kerst, J. M., de Jong, I. J., Groenewegen, G., van den Eertwegh, A. J. M., Poortmans, P. M., Klümpen, H.-J., van den Berg, H. A., Smilde, T. J., Vanneste, B. G. L., Aarts, M. J., Incrocci, L., van den Bergh, A. C. M., Jóźwiak, K., van den Belt-Dusebout, A. W., Horenblas, S., Gietema, J. A., van Leeuwen, F. E., & Schaapveld, M.
Affiliations
  • University Medical Center Groningen (NL)
  • Harmke J. Groot, Jan Martijn Kerst, Katarzyna Jóźwiak, Alexandra W. van den Belt-Dusebout, Simon Horenblas, Flora E. van Leeuwen, and Michael Schaapveld, Netherlands Cancer Institute; Alfons J.M. van den Eertwegh, Vrije Universiteit Medical Center; Heinz-Josef Klümpen, Academic Medical Center, Amsterdam; Sjoukje Lubberts, Igle J. de Jong, Alfons C.M. van den Bergh, and Jourik A. Gietema, University Medical Center Groningen, University of Groningen, Groningen; Ronald de Wit and Luca Incrocci, Erasmus...
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2018-08-20
Volume
36
Issue
24
Pages
2504-2513
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2017.77.4174
OpenAlex
W2865362922
Cited by
88
References
33
Citations by year
2026: 3 · 2025: 12 · 2024: 11 · 2023: 11 · 2022: 13 · 2021: 12 · 2020: 7 · 2019: 16 · 2018: 3
FWCI
7.45
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of Clinical Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
  • Research Publications (Maastricht University) (acceptedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
  • Research Publications (Maastricht University) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
  • Health Sciences › Medicine › Surgery › Testicular diseases and treatments
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
Keywords
testicular germ cell tumors, secondary malignancies, platinum-based chemotherapy, seminoma, non-seminoma, colorectal cancer, gastrointestinal cancer, cumulative incidence, cancer survivors, thyroid cancer, melanoma, soft tissue sarcoma, bladder cancer, lung cancer, pancreatic cancer, gastric cancer, colon cancer, small intestine neoplasms
MeSH terms
Adult, Antineoplastic Agents, Humans, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal, Netherlands, Radiotherapy, Testicular Neoplasms, Incidence, Neoplasms, Second Primary, Platinum Compounds

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