Long-term survival in patients with germ cell testicular cancer: A population-based competing-risks regression analysis

https://doi.org/10.1016/j.ejso.2013.09.019Get rights and content

Abstract

Backgrounds

Incidence of secondary malignancies and cardiovascular diseases among testicular germ cell tumor (TGCT) survivors is higher compared to the general population. We sought to describe the rates of other-cancer (OCM), non-cancer related (NCRM), and cancer-specific mortality (CSM) among men with TGCT.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER) database, 31,330 patients with a primary diagnosis of TGCT between 1973 and 2009 were identified. The primary endpoints comprised of 15-year CSM, OCM, and NCRM rates. Survival rates were stratified according to histology (seminoma vs. non-seminoma), median age (<34 vs. ≥34 years old), and disease stage (localized vs. regional vs. distant). Competing-risks Poisson regression methodologies were performed.

Results

For seminoma patients, the rates of CSM at 15 years increased with advancing stage (0.4–12.6%; P < 0.001), but varies little with age. In contrast, the rates of OCM (0.4–7.9%) and NCRM (2.9–8.9%) at 15 years increased with advancing stage and age (all P < 0.001). For non-seminoma patients, the 15-year CSM rates increased with advancing stage and age (1.9–24.4%; all P < 0.001). For the same time point, the rates of OCM (0.3–11.4%) and NCRM (2.4–8.0%) also increased with age and stage (all P ≤ 0.001).

Conclusions

The risk of dying from secondary malignancies or other causes significantly increases with advancing stage and age at diagnosis among TGCT survivors. Such information can help provide patients and physicians with better screening strategies, follow-up protocols, and mental preparedness for such undesirable effects.

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.

References (28)

  • G.K. Zagars et al.

    Mortality after cure of testicular seminoma

    J Clin Oncol

    (2004 Feb 15)
  • N. Howlader et al.

    SEER cancer statistics review, 1975–2009 (Vintage 2009 populations)

    (2011)
  • L.A.G. Ries et al.

    SEER cancer statistics review, 1975–2004

    (2004)
  • C.Y. Hu et al.

    Assessing the utility of cancer-registry-processed cause of death in calculating cancer-specific survival

    Cancer

    (2013 15)
  • Cited by (22)

    • Early ageing after cytotoxic treatment for testicular cancer and cellular senescence: Time to act

      2020, Critical Reviews in Oncology/Hematology
      Citation Excerpt :

      However, the median follow-up duration was only 10 years (Fosså et al., 2007). Another study showed a non-cancer related mortality rate of 3·2 % after a median follow-up of 15 years, but did not perform a comparison to the general population (Gandaglia et al., 2014). In Norwegian long-term TC survivors, an accelerated survival decline beyond 15–30 years of follow-up was evident.

    • Contemporary Assessment of Long-Term Survival Rates in Patients With Stage I Nonseminoma Germ-Cell Tumor of the Testis: Population-Based Comparison Between Surveillance and Active Treatment After Initial Orchiectomy

      2019, Clinical Genitourinary Cancer
      Citation Excerpt :

      For the purpose of our study, we relied on the Surveillance, Epidemiology, and End Results (SEER) database, which samples 26% of the United States and approximates the US population in its demographic composition as well as in its cancer incidence.15 We focused on men aged 18 years or older diagnosed between 1988 and 2015 with histologically confirmed testicular cancer (International Classification of Disease for Oncology [ICD-O] site codes C62.1, C62.9) and NSGCTT histology codes (9064, 9070-9071, 9080-9085, 9100-9102).3,16 We only considered patients with stage I NSGCTT who underwent orchiectomy.

    • Targeted treatment approaches in refractory germ cell tumors

      2019, Critical Reviews in Oncology/Hematology
    • Cost Analysis of Noninvasive Blood-Based MicroRNA Testing Versus CT Scans for Follow-up in Patients With Testicular Germ-Cell Tumors

      2019, Clinical Genitourinary Cancer
      Citation 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

    View all citing articles on Scopus
    1

    Both authors contributed equally.

    View full text