Elsevier

Brachytherapy

Volume 18, Issue 1, January–February 2019, Pages 29-37
Brachytherapy

Gynecologic Oncology
Increasing age predicts poor cervical cancer prognosis with subsequent effect on treatment and overall survival

https://doi.org/10.1016/j.brachy.2018.08.016Get rights and content

Abstract

Purpose

Stage and histology are well-established prognostic factors for cervical cancer, but the importance of age has been controversial and a clear role for this factor has not yet been defined. Thus, we aim with this study to evaluate the significance of age as an independent prognostic factor in women with cervical cancer and evaluate the therapeutic consequences and survival outcomes as they relate to this factor.

Methods and Materials

The Surveillance, Epidemiology, and End Results (SEER) database was used to retrospectively analyze patients diagnosed with cervical cancer from 1973 to 2013 in the United States. Data collected included demographics, tumor histology and stage, treatment details, and survival outcomes. Age was grouped into 20–49, 50–69, ≥70 years. Stage was localized (FIGO IA-IB1), regional (IB2-IVA), and distant (IVB). Treatments were classified as “aggressive” (surgery, external beam radiation therapy [XRT] + brachytherapy [BT], surgery + BT, surgery + XRT, or surgery + XRT + BT) or “nonaggressive” (XRT alone, BT alone, or no treatment). Statistical analysis performed on these data included the use of the Log-Rank test, χ2 analysis, and the Cox proportional hazards model.

Results

Forty-six thousand three hundred fifty women with cervical cancer were identified using the SEER database. 54% were aged <50 years, 33% 50–69 years, and 13% ≥70 years. Older women, particular those over age 70 years, show significantly decreased survival trends when stratified by stage and histology (p < 0.0001). Furthermore, taking stage, histology, race, and treatment into account, increasing age demonstrates negative prognostic significance with a hazard ratio of 2.87 for women over age 70 years and 1.46 for women aged 50–69 years. In addition, women over 70 years, regardless of stage, are significantly more likely to receive nonaggressive treatment regimens (<0.0001), or no treatment at all (p < 0.0001). Finally, older women gain a significant survival advantage from treatment, even with less-aggressive regimens, as compared with no treatment at all (p < 0.0001), with BT alone showing the greatest survival benefit (p < 0.0001 vs no treatment; p < 0.0087 vs XRT) among less-aggressive therapies. When evaluated by stage, BT continues to hold a significant survival advantage for localized, regional, and distant disease in individuals over age 70 years (localized: p = 0.0009 vs no treatment; regional and distant: p < 0.0001 vs no treatment), with both an overall survival and disease-specific survival benefit over XRT seen as well for women with distant disease (p < 0.0001).

Conclusions

Older women with cervical cancer show a poor overall survival trend that remains consistent among various stages and histologic subtypes. Risk analysis of this study population supports that age is an independent negative prognostic factor, even when accounting for stage, histology, and race. Furthermore, older women receive less-aggressive treatment as compared with their younger counterparts, with a significant number receiving no treatment at all. Despite this, older women still obtain a significant survival benefit with less-aggressive therapies, particularly with BT alone. Most interesting is that BT shows a survival benefit for older women among all cervical cancer stages, supporting the immense potential clinical benefit. In fact, women over 70 years with more advanced stage disease showed a significant survival benefit, both overall survival and disease-specific survival, with BT over external beam radiotherapy as well. Previous studies have created a foundation of literature, which shows that inclusion of BT in treatment regimens among all age groups improves survival and that older women in general are less likely to be adequately treated for cervical cancer. The novelty of this study lies in the fact that it demonstrates that older women, who we show are at risk for a poorer overall prognosis because of their age, are not only receiving appropriate treatment less often, they are also dying more frequently because of it. Our data support that older women are a high-risk group of patients who would benefit significantly from treatment, even if that treatment is BT alone. BT for cervical cancer is a tolerable procedure, even for most elderly women, and should, therefore, remain a standard clinical option for this population, regardless of their stage or histology at diagnosis.

Introduction

In 2017, there is estimated to be almost 13,000 cases of cervical cancer diagnosed, making it the third most common gynecologic malignancy (1). Although cervical cancer screening has helped dramatically in identifying disease at an earlier stage and reducing overall mortality, there is still estimated to be over 4000 women who will die from this disease in the United States this year [1], [2]. As a result, it is imperative that we continue to advance our understanding of both the disease process and of the most effective therapeutic practices.

There are a number of risk factors known to be associated with cervical cancer prognosis, including stage at diagnosis, histology, smoking, and race [1], [3], [4], [5]. Age as an independent prognostic factor for cervical cancer is a question that has been debated and evaluated in the literature without a clear, definitive answer. There is some evidence arguing that older age may serve as an independent factor for poor prognosis [6], [7], [8], whereas other studies have failed to find this association [9], [10]. We aim to evaluate this question using the Surveillance, Epidemiology, and End Results Program (SEER) database and determine the prognostic implication of age at diagnosis in women with cervical cancer. In addition, we aim to determine the impact of age on treatments received, clinical outcomes, and to determine implications for future treatment paradigms.

Section snippets

Patient population

SEER is an online database [11], [12] that aggregates cancer statistic data in the United States based on information from regional cancer registries. Using this resource, we obtained information on the diagnosis, treatment, and outcomes of women diagnosed with cervical cancer between the years of 1973 and 2015 in the United States. This study qualified for institutional review board approval exemption as the SEER data are already deidentified. A SEER program Data-Use agreement was submitted

Demographics

Forty-six thousand three hundred fifty women with cervical cancer were identified. Of these, 54% were aged <50 years, 33% 50–69 years, and 13% ≥70 years. Most patients were white (76%), had a localized stage (50%), and squamous cell histology (70%). Most women received aggressive therapy (75%) (Table 1).

Older women show poorer survival rates, regardless of disease stage

When looking at the total population, overall survival curves for women with cervical cancer tend to separate based on age, with increasingly poorer survival seen as women age (Fig 1a). There

Discussion

Although it is well established that the average age of cervical cancer diagnosis ranges from 35 to 44 years, with a median age of diagnosis of 49 years, there is still a significant number of older women who not only are diagnosed with cervical cancer but also die from it each year (1). From 2009 to 2013, 38% of cervical cancer cases occurred in women 55 years and older, with almost 20% of cases found in women greater than age 65 years [1], [2]. This information is particularly relevant given

Conclusion

As we and others have now shown, advancing age is an independent negative prognostic factor for mortality for women with cervical cancer. It is imperative that we reevaluate our clinical decision-making and not compromise standard of care in the setting of an elderly patient. We acknowledge that each patient is unique and presents with their own set of circumstances that may alter their ability to receive standard of care treatment, but we urge clinicians to strive to achieve this standard in

Acknowledgments

Services and products in support of this research project were generated by the VCU Massey Cancer Center Biostatistics Shared Resource, supported, in part, with funding from NIH–NCI Cancer Center Support Grant P30 CA016059.

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