Ovarian cancer in the octogenarian: Does the paradigm of aggressive cytoreductive surgery and chemotherapy still apply?
Commentary by Dr Christopher Steer
The article:
Moore KN., Reid MS., Fong DN., et al. Ovarian cancer in the octogenarian: Does the paradigm of aggressive cytoreductive surgery and chemotherapy still apply? Gynaecologic Oncology 2008:110(2):133-9.
The reviewer:
Dr Christopher Steer is a Medical Oncologist at Border Medical Oncology, Albury-Wodonga.
Summary
Abbreviations
Cytoreductive surgery (CRS), Epithelial ovarian cancer (EOC)
Study Design
This retrospective analysis of patients treated in a single centre between 1991 and 2006 aimed to examine the experience of treating very elderly women (>80yrs) with ovarian cancer. The study examined post-operative complications, chemotherapy received and overall survival. Patient data collected from records included: age at diagnosis, primary treatment modality, residual tumour after cytoreductive effort and post-operative complications. Charlson co-morbidity scores were calculated, and details of chemotherapy were collected, including time to initiation, agent selection, number of cycles, toxicity and response.
Findings
A total of 85 patients diagnosed with epithelial ovarian cancer (EOC) at age 80 years or older were identified from a database of over 600 consecutive patients treated at the University of Oklahoma between 1991 and 2006. The median age of this group at diagnosis was 83 years with a range of 80-95 years. Seventy percent of the cohort had at least one and 30% had two or more co-existing medical co-morbidities. Eighty five percent of patients presented with advanced (FIGO stage III/IV) disease.
It was noted that primary cytoreductive surgery with anticipated chemotherapy to follow was attempted in the majority of patients (80%). Chemotherapy alone was given to 15 patients (18%) and neoadjuvant therapy with interval cytoreductive surgery to 2 patients (2%). Among the 70 patients who underwent primary surgical exploration, two were stage IA and required no further therapy. Of the patients who underwent surgery for advanced disease, optimal cytoreduction was achieved in 74%. Radical procedures were utilised in 41% including 23 patients who underwent bowel resection.
Postoperative complications were frequent. Thirteen percent of patients who underwent primary surgery died during the initial hospitalization. Seven of these experienced delirium and oliguria and died without a clear cause being found. Eight patients (12%) received no adjuvant therapy after surgery; four of these patients died during their post-operative course and the additional four patients never recovered enough to tolerate adjuvant therapy. The majority of patients who received some adjuvant therapy were treated with combination paclitaxel and a platinum agent (73%). Two percent of patients were treated with platinum and cyclophosphamide and 25% were treated with single agent platinum. Of those who began chemotherapy, 43% completed 3 or fewer cycles, while 51% completed 6 or more cycles. Seventeen percent of patients were treated as part of a clinical trial.
Median follow-up for patients who underwent primary surgical staging was 17.5 months compared with 16 months for primary chemotherapy group. Two year overall survival for primary surgery group was 51% (stage III patients, no stage IV who underwent primary surgery lived beyond 1 month) compared with 27% for primary chemotherapy group (p=0.08). Twenty-six percent of patients treated with primary chemotherapy were deceased within two months after diagnosis. Self reported toxicities were relatively uncommon in this age group; with the most common being fatigue (25%), abdominal pain (14%) and extremity numbness (7%). The median length of hospital stay was 8 days, with a range of 2 to 54 days.
Conclusion
The authors concluded that their data suggest that patients >80yrs may not tolerate combination surgery and chemotherapy. The extremely high proportion of post-operative complications and relatively high proportion of post-operative deaths argues for a more prudent approach to this group of patients. Future research will help clinicians better determine which patients in this age group are fit enough to tolerate primary surgery followed by adjuvant therapy, versus those patients for whom palliation of symptoms and shorter term maintenance of quality of life are more important priorities. For these patients, some variation in the current paradigm is warranted.
Commentary
What does this article add to existing clinical evidence in this area?
The title of this article captures the essence of a problem that clinicians will face increasingly in the future. It is well known that our population is ageing. Life expectancy is increasing, and the number of people in the older age groups is also growing. A United Nations report on our ageing global population states: “The fastest growing age group in the world is the oldest-old, those aged 80 years or older. They are currently increasing at 3.8 per cent per year and comprise more than one tenth of the total number of older persons. By the middle of the century, one fifth of older persons will be 80 years or older.”1
The authors of this article have attempted to describe the difficulties associated with the treatment of ovarian cancer in the oldest-old. The age cut-off used to define the term “elderly” varies between studies and specific trials of patients over the age of 80 years are very rare. Another retrospective review performed by Cloven and colleagues in 1999, albeit of only 18 patients, described similar findings.2
Most published studies on this topic focus on the tolerability of either surgery or chemotherapy. It is generally accepted that fit elderly patients manage chemotherapy with acceptable toxicity and there is no difference in regard to response when compared with cohorts of younger patients.3 Retrospective trials in young-old patients (>65 years) have shown that fit elderly patients tolerate surgery and chemotherapy equally as well as their younger counterparts but survival is impacted if ‘suboptimal’ therapy is given.4
In challenging the paradigm of aggressive up-front cytoreduction for all patients, this study seems to confirm clinicians’ suspicions regarding the appropriateness of this approach in the oldest-old. The majority of patients with advanced disease underwent primary surgery however, this population may be better treated with neoadjuvant chemotherapy followed by interval debulking. They are then in a much fitter state medically, and able to withstand aggressive cytoreductive surgery without the morbidity and mortality reported in this study. Other factors which may have an impact on survival are the presence of co-morbidities, tumour stage and treatment in a non-specialist facility.4
In describing a series of patients who have all been treated in the one facility, the authors conclude that patients over the age of 80 face an unacceptably high rate of morbidity and mortality after cytoreductive surgery. In addition, the increased time that is often required to recover leads to a decrease in the utility of adjuvant chemotherapy. This may be one of the factors which leads to a less than optimal outcome.
How adequate was the methodology used in addressing the aims of this study?
This is a retrospective review of treatment performed in a single centre. It is the largest such descriptive trial recorded but remains relatively small and it is therefore not possible to draw accurate or detailed conclusions. The study appears thorough in its data collection but is inherently limited by its design. Although detailed patient data appears to have been collected, there was little information available regarding the reasons for initial treatment decisions.
What are the implications of this study for clinical practice in Australia?
At best this study should be considered hypothesis generating. It raises more questions than it provides answers. The authors should be commended for describing a case series in which the outcomes from treatment would appear to be suboptimal. The treatment paradigm employed by clinicians at this institution would appear to require modification. It could be argued from this study that radical cytoreductive procedures in the oldest-old can cause unacceptable morbidity and mortality.
The results of this review suggest that improvements are required in the patient selection process. Prospective studies employing comprehensive geriatric assessment to assist in the triage of patients are required. Alternative therapy such as optimally-dosed primary chemotherapy may be more appropriate in the oldest-old than aggressive cytoreductive surgery.
References
- United Nations Department of Economic and Social Affairs Population Division. World Population Ageing: 1950-2050; 2007.
- Cloven NG, Manetta A, Berman ML, Kohler MF, DiSaia PJ. Management of ovarian cancer in patients older than 80 years of Age. Gynecol Oncol 1999;73(1):137-9.
- Eisenhauer EL, Tew WP, Levine DA, Lichtman SM, Brown CL, Aghajanian C, Huh J, Barakat RR, Chi DS. Response and outcomes in elderly patients with stages IIIC-IV ovarian cancer receiving platinum-taxane chemotherapy. Gynecol Oncol 2007;106(2):381-7.
- Janda M, Youlden DR, Baade PD, Jackson D, Obermair A. Elderly patients with stage III or IV ovarian cancer: should they receive standard care? Int J Gynecol Cancer 2008;18(5):896-907.
Editor: Ms Alison Pearce, Program Manager, National Breast and Ovarian Cancer Centre.
Editorial Committee: Prof Michael Friedlander – Medical Oncologist, Prof Neville Hacker – Gynaecological Oncologist, Dr Gillian Mitchell – Medical Oncologist, Dr Deborah Neesham – Gynaecological Oncologist, Ms Georgie Richter – Gynaecological Nurse.
Disclaimer
Clinical Update - Ovarian Cancer is produced by the National Breast and Ovarian Cancer Centre (NBOCC) and is intended to provide health professionals with timely expert commentary on new research in ovarian cancer. Commentaries included in Clinical Update - Ovarian Cancer do not replace recommendations included in NBOCC clinical practice guidelines.
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