Long-term survival in patients with germ cell testicular cancer: A population-based competing-risks regression analysis
Introduction
Testicular germ cell tumor (TGCT) represents one of the most curable malignancies, with an overall 10-year cancer-specific mortality (CSM)-free survival rate approaching 95%.1 Whereas survival has been maximized over the last decades, the long-term sequelae among testicular cancer survivors are well established. Namely, the risks of secondary malignant neoplasms and cardiovascular disease are considerable.2, 3, 4, 5, 6 For example, the excess risk of a second malignant organ among testicular cancer survivors according to an international population-based survey ranged from 1.5 to 4.0 after 10-years of follow-up (n = 40,576).3 Particularly, for patients treated with radiotherapy alone, the risks of a second malignant neoplasm in typical infradiaphragmatic fields were up to 2.7 times higher compared to non-exposed radiotherapy sites.3
The consideration of such adverse outcomes (i.e. secondary malignancies and cardiovascular disease) is of particular clinical relevance for men with TGCT, since the disease is diagnosed at a young age, where patients have an average life expectancy beyond 30 years following treatment.1, 7 In that regard, the occurrence of such adverse events may ultimately compromise patients' quality of life despite a complete remission from TGCT, and may possibly result in an undesirable life-threatening endpoint. As such, the characterization of other-cancer mortality (OCM) and non-cancer related mortality (NCRM) might be worthwhile for both patients and physicians during treatment decision and surveillance planning.
Although previous studies reported higher risk of secondary malignancies and cardiovascular diseases among TGCT survivors,5, 8 no study has systematically explored the risks of such endpoints after stratifying patients according to age and stage. To address this void, we sought to describe the rates of OCM, NCRM, and CSM at 15 years after TGCT diagnosis in a large retrospective population-based cohort. Due to the paucity of events given the long life expectancy of such patients, we relied on Poisson regression analyses, where to simultaneously account for all examined endpoints, competing-risks regression analyses were performed.
Section snippets
Population source
The Surveillance, Epidemiology, and End Results (SEER) program database comprising of 18 registries was used to extract the study population. The SEER routinely collects patient demographics, and publishes cancer incidence and survival data from population-based cancer registries, covering approximately 28% of the United States population.9 The characteristics of the SEER population are comparable with that of the general population of the United States.10
Study cohort
Patients with a primary diagnosis of
Baseline descriptive
Overall 31 330 patients with TGCT who underwent orchiectomy between 1973 and 2009 were identified (Table 1). Average age at diagnosis was 34.7 years (median: 33, interquartile range 27–41). The majority of patients were white (92.5%). Most harbored localized disease (71%). Respectively 18,263 (58.3%) and 13,067 (41.7%) individuals had seminoma and non-seminoma TGCT. Statistically significant differences in age at diagnosis, race, year of diagnosis and stage were recorded between the two groups
Discussion
The near 100% survival of testis cancer patients is partially mitigated by the non-negligible increased risks of secondary malignant neoplasms and cardiovascular diseases attributable to chemotherapy and radiotherapy.2, 3, 4, 5, 6, 8 Such long-term effects usually occur with a latency of at least 10 years following treatment of TGCT.15 As a better understanding of the specific pathophysiological mechanisms behind the development of such long-term treatment effects among TGCT survivors unfolds,7
Role of the funding source
No founding or other financial support was received.
Conflict of interest statement
None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
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2019, Clinical Genitourinary CancerCitation Excerpt :It should be noted that death was only modeled after a transition into the relapse state, supported by the low mortality rates from active TGCT disease and the high success rates of treatment.25 In the United States, according to the Surveillance, Epidemiology, and End Results database, 58.3% of TGCT patients have seminoma and 41.7% nonseminoma.26 Year 0 starting stages were based on the distribution of tumor stages at diagnosis.26
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Both authors contributed equally.