ABSTRACT: The incidence of ovarian carcinoma increases with advancing age, peaking during the 7th decade of life and remaining elevated until age 80 years. Despite the high prevalence of ovarian cancer in the elderly, the management of these patients is often less aggressive than that of their younger counterparts. As a result, many elderly cancer patients receive inadequate treatment. However, data do not support the concept that age, per se, is a negative prognostic factor. In fact, the majority of elderly patients are able to tolerate the standard of care for ovarian cancer including initial surgical cytoreduction followed by platinum and taxane chemotherapy. Because functional status has not demonstrated a reliable correlation with either tumor stage or comorbidity, each patient’s comorbidities should be assessed independently. For elderly patients with significant medical comorbidity, the extent of surgery and aggressiveness of chemotherapy should be tailored to the extent of disease, symptoms, overall health, and life goals. In addition, enhanced cooperation between geriatricians and oncologists may assist the pretreatment assessment of elderly patients and improve treatment guidelines in this population.
Dramatic improvements in health care and a decrease in mortality have resulted in an increase in life expectancy among people living in developed countries. In Western countries, a woman's life expectancy was 81.1 years in 1991 and is expected to reach 90.4 years by 2020.[1,2] As a result, the number of cancer-bearing patients aged 70 years and older may also be expected to increase.[3-5] The incidence of ovarian carcinoma rises with advancing age, peaks during the 7th decade of life, and remains elevated until age 80 years . Malignant ovarian neoplasms manifest after age 65 in 30% to 40% of patients.[6,7] Despite the high prevalence of this disease in the elderly, the management of these patients is often less aggressive than that of their younger counterparts, with the result being that many elderly patients receive inadequate treatment.[8-12]
Standard Management for Ovarian Cancer
Approximately 75% of patients with epithelial ovarian cancer are diagnosed when their disease has spread throughout the peritoneal cavity. Most commonly, patients will present with abdominal discomfort or pain. This is generally followed closely by abdominal distention due to the presence of intra-abdominal masses and/or malignant ascites. Gastrointestinal symptoms are nonspecific but include nausea, early satiety, constipation or obstipation, and, less frequently, urinary symptoms. If disease has progressed to involve the lungs by the presence of pulmonary metastases or malignant pleural effusions, the patient may complain of shortness of breath and lethargy.
The 5-year survival of patients with epithelial ovarian cancer correlates directly with tumor stage. The International Federation of Gynecology and Obstetrics (FIGO) staging system, revised in 1985, is presented in Table 1. With the exception of stage IV disease, which can be diagnosed by a cytologically positive pleural fluid, computed tomography-guided biopsy of intraparenchymal liver lesions, or other pathologic evidence of distant spread, the stage of disease is only accurately determined by an exploratory surgical assessment (ie, laparotomy or laparoscopy).
Laparotomy should be performed through a vertical midline incision to allow access to the upper abdomen. Peritoneal lavage or aspiration of ascites is performed to obtain specimens for cytologic analysis. Suspicious areas throughout the abdomen and pelvis, including adhesions, should be biopsied with separate specimens obtained from the pelvis, right and left paracolic gutters, and the undersurfaces of the right and left hemidiaphragms. All intestinal surfaces should be evaluated, and an omentectomy with random peritoneal biopsies should be performed. Pelvic and aortic lymph node sampling is also required.
When the staging is thorough and methodical, a significant number of patients initially thought to have localized disease will be upstaged. In a report by Young and colleagues, 31% of women thought to have stage I or II disease at initial surgery were upstaged at repeat surgical staging. Of these patients, 77% were upstaged to stage III. In a report by McGowan et al, gynecologic oncologists performed adequate surgical staging in 97% of cases, compared to 52% of cases for obstetrician/gynecologists and 35% of cases for general surgeons. In this report, 46% of the 291 women evaluated, had been inadequately staged.
In addition to the prognostic importance of accurate staging, surgical cytoreduction (or debulking) has proven to be an integral component in the management of epithelial ovarian cancer. The volume of residual disease following cytoreductive surgery is inversely related to survival.[16-19] Current criteria for optimal cytoreduction imply residual tumor nodules no greater than 1 cm in diameter. Patients who have undergone optimal cytoreduction have approximately a 22-month median survival advantage compared to patients with suboptimal cytoreduction (residual disease > 1 cm in maximum diameter). Hoskins and colleagues analyzed data from the Gynecologic Oncology Group and noted a significant improvement in survival among patients with 1- to 2- cm residual disease compared to those with greater than 2-cm residual disease.[ 20]
In addition to the survival benefits of cytoreductive surgery, recent reports also confirm that aggressive primary cytoreductions are associated with minimal morbidity and mortality when performed by experienced surgeons. Most studies supporting the survival benefit of cytoreductive surgery have enrolled patients with both stage III and IV disease. Four recent retrospective reports have examined cytoreductive surgery separately in patients with stage IV disease and have consistently demonstrated a statistically significant improvement in survival when a small volume of residual disease remains.[22-24]
Surgery alone rarely produces cure in ovarian cancer patients. Chemotherapy agents from a wide variety of classes have demonstrated activity against ovarian cancer. With the establishment of platinum-based therapy and the introduction of the taxanes, the past 2 decades have seen dramatic improvements in response to chemotherapy and progression-free survival.
Paclitaxel was reported to have significant activity in advanced ovarian carcinoma in 1989. After a series of phase I and II trials established the activity of paclitaxel(Drug information on paclitaxel), two prospective randomized trials comparing cisplatin plus paclitaxel vs cisplatin plus cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar) demonstrated the superiority of the paclitaxel-containing regimen.[26,27] Subsequent prospective randomized trials compared paclitaxel/carboplatin (Paraplatin) vs paclitaxel/cisplatin, demonstrating decreased toxicity with the carboplatin(Drug information on carboplatin) regimen and no difference in efficacy.[28,29] With these results, paclitaxel plus carboplatin is now considered first-line treatment for most patients with advanced ovarian cancer.
Patterns of Care
In one of the earliest published reports to examine patterns of care among elderly patients with ovarian cancer, Ries analyzed data for over 22,000 women diagnosed between 1973 and 1987 within the Surveillance, Epidemiology, and End Results (SEER) program. When stratified by stage, age was a significant determinant of survival. The 5-year survival rate for women less than age 45 was 45%, compared to 8% for those age 85 and over. Over 40% of women over 85 did not receive definitive treatment for their disease. In addition, when treatment was given, younger women received multimodality therapy more often than did their older counterparts, who received more single-modality treatments such as surgery, chemotherapy, or hormonal therapy alone.
Further evidence that older women received less aggressive therapy and had poorer survival rates was published in 1994. Hightower and colleagues[ 12] analyzed data from the American College of Surgeons Cancer Commission to investigate differences in patterns of care among the elderly. This study compared survival and care in two patient groups- those age 80 or older vs those under 80. Of 12,316 patients diagnosed between 1983 and 1988, 1,115 were at least 80 years old. Survival was significantly lower among patients in the older group. Most elderly ovarian cancer patients were cared for by nononcologists such as general surgeons (31%) and obstetrician/gynecologists (29%). They also received fewer total abdominal hysterectomies, bilateral salpingo-oophorectomies, and omentectomies than their younger counterparts. Optimal tumor debulking rates were significantly lower for women age 80 or older, and these patients were less likely than younger patients to be given adjuvant chemotherapy (42% vs 69%, P < .0001).
It was recently reported that, although 60% of cancers arise in people over age 65, only 20% to 40% of these patients are enrolled in phase II and III trials, and the majority of patients in these trials are less than age 70.[30,31] Markman et al reported on the Memorial Sloan-Kettering Cancer Center experience regarding enrollment of women with ovarian cancer into clinical trials after primary surgical therapy. A total of 46% of the younger patients were entered into an intensive initial chemotherapy trial, compared to 17% of older patients. The reported reason for the lower enrollment of older patients was an excessive prevalence of comorbid conditions such as heart disease. In addition, the rate of referrals to this institution for both initial treatment and salvage therapy was fourfold higher among younger women compared to their older counterparts. This observation suggests that older patients are less likely to be referred for secondary experimental programs.
Recent reports have also demonstrated that older women with ovarian cancer are less likely to receive the standard recommended treatment or be seen by a gynecologic oncologist in the course of their treatment.[ 34] Carney and colleagues conducted a statewide populationbased study in Utah between 1992 and 1998. Among the 848 cases of epithelial ovarian cancer identified, fewer than 25% of women over age 70 were seen by a gynecologic oncologist, compared to 55% of women aged 40 to 59 and 42.6% of those aged 60 to 69. In the same study, patients with advanced disease experienced a significant survival advantage when a gynecologic oncologist was involved in their care.