Elsevier

Gynecologic Oncology

Volume 127, Issue 2, November 2012, Pages 367-374
Gynecologic Oncology

Significance of age and comorbidity on treatment modality, treatment adherence, and prognosis in elderly ovarian cancer patients

https://doi.org/10.1016/j.ygyno.2012.07.001Get rights and content

Abstract

Background

Age is associated with poor prognosis in ovarian cancer patients. Reasons could be increased comorbidity, more advanced stage, or nonoptimal surgery or chemotherapy. Objectives of this study were to evaluate the significance of comorbidity and age ≥ 70 years on receiving cytoreductive surgery, standard combination chemotherapy (TC), adherence to TC treatment, and prognosis.

Methods

A retrospective cohort study of all women registered in a nation-wide database with ovarian or peritoneal cancer in 2005–2006. Logistic regression was employed for determining the predictive value of age and comorbidity (ASA score) on receiving cytoreductive surgery and TC, and on adhering to TC. Kaplan–Meier method and Cox proportional hazards analysis were employed for survival analyses.

Results

Of 961 patients, 348 (36.2%) were elderly. Age ≥ 70 years was independently predictive of not receiving surgery, OR 0.2(95% CI 0.1–0.5) and TC treatment, OR 0.03 (95% CI 0.01–0.1). Comorbidity was also independently predictive of not receiving standard treatment: OR for receiving surgery with ASA score of ≥ 3 was 0.2 (95% CI 0.1–0.5), and for receiving TC it was 0.03 (95% CI 0.01–0.1). Overall, age ≥ 70 was a poor prognostic factor in OS and PFS, but the effect of age ceased after 16 months. Comorbidity was a poor prognostic factor throughout the study period but with time-varying effect. For patients treated with TC, age was not a prognostic factor, whereas ASA score ≥ 3 was.

Conclusion

Elderly patients and patients with comorbidity less often receive optimal surgical and medical treatment. For those receiving optimal treatment, age ≥ 70 is not an independent poor prognostic factor, whereas severe comorbidity is.

Highlights

► Age ≥ 70 and comorbidity highly influence whether patients are offered surgery and standard chemotherapy (CT). ► In patients treated with standard CT, neither age ≥ 70 nor comorbidity, influences ability of adhering fully to treatment. ► Age ≥ 70 and comorbidity are associated with poor survival, but with time-varying effect.

Introduction

Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecologic cancer in the western world [1]. In Denmark the incidence of EOC has been rather stable during the past 20 years with approximately 580 new cases per year. The incidence and mortality of EOC increases with age and both peak at 75–79 years [2].

Age itself has been found to be a poor prognostic factor in patients with EOC [3], [4], [5], [6]. The reasons are not fully clarified. It could be factors such as comorbidity, more advanced stage at diagnosis, toxic effects of chemotherapy or that the elderly patients are withheld optimal surgery or chemotherapy.

The recommended treatment of EOC is upfront CRS and for all patients, except those with FIGO stage IA–IB grade 1 disease, followed by combination chemotherapy with carboplatin and a taxane (TC), 6 cycles administered every t3 weeks. In primary inoperable patients, three courses of neoadjuvant chemotherapy followed by interval debulking and then followed by another three courses of chemotherapy is an option. This treatment became standard after the GOG-111 and OV-10 both finding paclitaxel to be more effective than cyclophosphamide in combination therapy with cisplatin, and a meta-analysis of 37 randomised trials concluding that cisplatin and carboplatin are therapeutically equivalent in treatment of women with advanced EOC [7], [8], [9], [10]. Finally, TC was shown to be as effective as and less toxic than cisplatin and paclitaxel [11], [12], [13]. In these studies, however, median age did not exceed 60 years. Clinical trials directed specifically towards elderly cancer patients are scarce, and except for small-scale phase II trials, non‐existing for ovarian cancer.

The objectives of this study were to evaluate the significance of comorbidity and age on receiving cytoreductive surgery, standard combination chemotherapy (TC) , adherence to TC treatment, and finally, to estimate progression-free and overall 5-year survival.

Section snippets

Material and methods

The study is a retrospective cohort study. All Danish women who had a diagnosis of epithelial cancer of the ovaries or peritoneum in Denmark in 2005 and 2006 were included in the study. Data on these women were obtained from The Danish Gynecological Cancer Database (DGCD), The Danish Cancer Register (DCR), the Danish Causes of Death Register (DCDR), the National Register of Persons (NRP), and from the medical charts of the patients. Linkage of all data sources was performed via the personal

Results

We identified 979 patients in the DGCD with an incident diagnosis of cancer of the ovaries or peritoneum from January 1, 2005 to December 31, 2006. Of these, 18 were excluded: two were found not to have OC and 16 did not have epithelial OC.

A further 228 patients were identified in the DCR (Fig. 1). After manual review (by the DGCD), 83 of these could be excluded, either because they did not have EOC, or because they were registered in the DGCD as having a first time diagnosis of OC either

All patients

Of 961 patients, 629 (65%) had died at the end of the study period; of these, 554 (88%) died from progressive disease, 35 (6%) died within 30 days after surgery, and four patients (1%) died from acute toxicity. Twenty-one patients (3%) died from causes not related to the cancer disease and 15 patients (2%) died from unknown causes. Median overall survival (OS) of all women < 70 and ≥ 70 years was 50 and 18 months, respectively (log-rank test: P < 0.0001. Median progression-free survival (PFS) was 19

Discussion

In this study, we found that ovarian cancer patients aged ≥ 70 years are at a much higher risk of being excluded from surgical or medical therapy. These patients had a higher ASA score and they more often presented with advanced disease. When operated, they were less often optimally debulked. When treated according to the chemotherapy guidelines, elderly patients more often had dose reductions and discontinued treatment early. Although younger patients had a better prognosis, elderly benefited

Conflict of interest statement

The authors declare that there are no conflicts of interest. The work was supported by the Danish Cancer Society, the I.M. Daehnfeldt Foundation, and The Danish Health Insurance Foundation. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Acknowledgements

We would like to thank all who contributed to this work. Especially, we would like to thank Karina Dahl Steffensen, MD, PhD and Yvette Schandorf Sørensen, RN, both from Vejle Hospital for their help with the data collection.

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