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年龄增长预示着宫颈癌预后不良,进而影响治疗和总体生存。

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

作者信息

Quinn Bridget A, Deng Xiaoyan, Colton Adrianne, Bandyopadhyay Dipankar, Carter Jori S, Fields Emma C

机构信息

Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA.

Department of Biostatistics, Virginia Commonwealth University, Richmond, VA.

出版信息

Brachytherapy. 2019 Jan-Feb;18(1):29-37. doi: 10.1016/j.brachy.2018.08.016. Epub 2018 Oct 22.

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, χ 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.

摘要

目的

分期和组织学是宫颈癌公认的预后因素,但年龄的重要性一直存在争议,且该因素的明确作用尚未确定。因此,我们开展本研究旨在评估年龄作为宫颈癌患者独立预后因素的意义,并评估与该因素相关的治疗效果和生存结局。

方法和材料

利用监测、流行病学和最终结果(SEER)数据库对1973年至2013年在美国诊断为宫颈癌的患者进行回顾性分析。收集的数据包括人口统计学信息、肿瘤组织学和分期、治疗细节以及生存结局。年龄分为20 - 49岁、50 - 69岁、≥70岁。分期分为局限期(国际妇产科联盟[FIGO]IA - IB1期)、区域期(IB2 - IVA期)和远处转移期(IVB期)。治疗分为“积极”(手术、外照射放疗[XRT]+近距离放疗[BT]、手术+BT、手术+XRT或手术+XRT+BT)或“非积极”(单纯XRT、单纯BT或未治疗)。对这些数据进行的统计分析包括使用对数秩检验、χ分析和Cox比例风险模型。

结果

使用SEER数据库确定了46350例宫颈癌女性患者。54%的患者年龄<50岁,33%为50 - 69岁,13%≥70岁。年龄较大的女性,尤其是70岁以上的女性,按分期和组织学分层时生存趋势显著下降(p<0.0001)。此外,综合考虑分期、组织学、种族和治疗因素,年龄增加显示出负面的预后意义,70岁以上女性的风险比为2.87,50 - 69岁女性为1.46。另外,70岁以上的女性,无论处于何分期,接受非积极治疗方案的可能性显著更高(<0.0001),或根本不接受治疗(p<0.0001)。最后,与根本不治疗相比,年龄较大的女性即使采用不太积极的治疗方案也能从治疗中获得显著的生存优势(p<0.0001),在不太积极的治疗方法中,单纯BT显示出最大的生存获益(与未治疗相比p<0.0001;与XRT相比p<0.0087)。按分期评估时,BT在70岁以上的局限期、区域期和远处转移期患者中仍具有显著的生存优势(局限期:与未治疗相比p = 0.0009;区域期和远处转移期:与未治疗相比p<0.0001),对于远处转移期女性,BT在总生存和疾病特异性生存方面也优于XRT(p<0.0001)。

结论

老年宫颈癌女性总体生存趋势较差,在不同分期和组织学亚型中均保持一致。对该研究人群的风险分析支持年龄是一个独立的负面预后因素,即使考虑到分期、组织学和种族。此外,与年轻女性相比,老年女性接受的治疗不太积极,相当一部分根本未接受治疗。尽管如此,老年女性采用不太积极的治疗方法仍能获得显著的生存获益,尤其是单纯BT。最有意思的是,BT在所有宫颈癌分期中对老年女性均显示出生存获益,支持其巨大的潜在临床益处。事实上,70岁以上处于更晚期疾病的女性,在总生存和疾病特异性生存方面,BT均显著优于外照射放疗。以往的研究奠定了文献基础,表明在所有年龄组的治疗方案中纳入BT可提高生存率,且一般而言老年女性宫颈癌的治疗不足。本研究的新颖之处在于,它表明老年女性由于年龄因素总体预后较差,不仅接受适当治疗的频率较低,而且因此死亡的频率也更高。我们的数据支持老年女性是高危患者群体,即使仅采用BT治疗也能从治疗中显著获益。宫颈癌的BT治疗即使对大多数老年女性也是可耐受的,因此,无论其诊断时的分期或组织学如何,都应仍然是该人群的标准临床选择。

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