ABSTRACT: Pancreatic cancer is a disease seen predominantly in elderly patients. Compared to younger patients, older patients are more likely to present with early-stage disease and, therefore, may be candidates for aggressive local treatment. Little published information exists on treatment outcomes for elderly patients with potentially resectable disease or those with locally advanced or metastatic pancreatic cancer. The limited information available suggests that elderly patients are as likely to benefit from surgery, radiation, and chemotherapy as younger patients. Despite this apparent benefit, elderly patients appear to have a worse long-term outcome. This may be due to the failure to offer them aggressive treatment or to comorbid conditions. Nevertheless, further studies need to be conducted in this area, and greater emphasis needs to be placed on including elderly patients in clinical trials. For elderly patients with terminal disease, there should be better use of palliative measures that may be of benefit. Each of these issues is discussed in detail. [ONCOLOGY 15(7):926-937, 2001]
By 2030, 20% of the population will be over 65 years of age. As the elderly population increases, oncologists will be faced with a progressively larger number of older patients with cancer. Pancreatic cancer is seen predominantly in older people, with incidence peaking from age 70 to 79 years. According to the National Cancer Database, 68.5% of pancreatic cancers were diagnosed in those over age 65 years. Overall, it is the fourth most common cause of cancer death, with an estimated 28,200 deaths in 2000. However, this is mainly because it is the fourth most common cause of cancer death in patients over age 55 years.
Older patients are more likely to have earlier-stage disease, but are less likely to undergo pancreatectomy. A recent report showed that in those under age 55 years, 22.5% underwent pancreatectomy, compared to 13.5% in those aged 70 to 74 years, 10.7% in those aged 75 to 79, and 6.3% in those over age 80. Older patients are also less likely to receive chemotherapy than younger patients. Although some of these patients are poor candidates for aggressive therapy, there is evidence from other tumor types that elderly patients do not receive appropriate treatment based on age alone.[5-8]
Despite the fact that the majority of patients with pancreatic cancer are elderly, there are very few data in the literature specific to this group of patients. Most of the existing data come from clinical trials, in which elderly patients are vastly underrepresented.[9,10] More research is needed to expand our knowledge of the treatment of pancreatic cancer in elderly patients, as the size and life expectancy of this population is ever increasing. This article will review the existing literature on the presentation and surgical and medical treatment of pancreatic cancer in elderly patients.
Characteristics of Pancreatic Cancer in the Elderly
Several studies have shown that older patients are less likely to be staged than younger patients.[2,3] Among those who are staged, it appears that older patients present with earlier-stage disease. Despite this fact, older patients have a worse overall 5-year survival compared to younger patients (Table 1). This may be due to less aggressive treatment of elderly patients, as well as deaths due to comorbid conditions. However, no studies are available that adequately address this issue.
Kamisawa et al examined the pathologic features of pancreatic cancer in 89 elderly patients (> 70 years) and compared them to 184 younger patients. With advancing age, proportionally more women were diagnosed. There were no differences in the grade or location (head/body/tail) of tumors in younger vs older patients, and there was no difference in the incidence of local spread. Elderly patients, however, did have fewer hematogenous metastases than younger patients.
In another study, it appeared that older patients had more diploid tumors, and younger patients had more aneuploid tumors (which may help explain the difference in hematogenous spread).
Various events have been implicated in the pathogenesis of pancreatic cancer, such as K-ras mutation and p53 tumor-suppressor gene mutation. Sato et al studied the expression of p53 mutations in paraffinized tumors by using monoclonal antibodies to products of the p53 gene, DO-1-p53. Overexpression of this product was significantly associated with a worse prognosis and was more common in older patients, independent of stage. The authors suggested that p53 mutations may be more common with aging. More research is needed to determine how aging is involved in the pathogenesis of pancreatic and other cancers.
The only potentially curative approach for pancreatic cancer is resection. Recent studies report 5-year survival rates ranging from 20% to 25% for those undergoing surgical resection.[2,14] Unfortunately, less than 20% of patients are considered resectable. With improvements in surgical techniques, the mortality for pancreaticoduodenectomy has diminished, and many centers are now reporting operative mortality rates of less than 5%. Although elderly patients present with earlier-stage disease, fewer of them undergo surgical treatment.
A number of centers have reported their experience in elderly patients, and have shown that pancreatic resection can be performed in elderly patients without excess mortality, even in those over age 80 years. Fong et al compared the outcomes of patients under age 70 to those age 70 and older undergoing pancreatic resections. Overall perioperative mortality was 6%. Although fewer patients over age 80 were scheduled for surgery, this group actually had fewer complications and no perioperative mortality. There was no difference in the length of hospital stay, complication rates, mortality rates, or rate of admission into the intensive care unit between age groups.
Univariate analysis showed that a history of cardiopulmonary disease, abnormal ECG, or abnormal chest x-ray preoperatively predicted for complications in elderly patients. Elderly patients did have a slightly lower median (18 vs 24 months) and 5-year survival (21% vs 29%). Other authors report similar survival rates for elderly patients compared to younger patients after surgery.[16-20] Morbidity and mortality data from recent surgical series in older patients are summarized in Table 2.[15-27]
Even less data are available for octogenarians. Sohn et al compared the outcomes of 46 patients over age 80 undergoing pancreaticoduodenectomy with 681 patients younger than 80. Mortality was similar for the older and younger groups (4.3% vs 1.6%, respectively, P = NS), however, there were more postoperative complications and longer hospital stays among the older patients. Median survival for patients with pancreatic adenocarcinomas was no different between age groups (17 vs 18 months in the younger group). Elderly patients who undergo pancreaticoduodenectomy are a highly selected group; however, these studies show that this procedure can be performed without excess morbidity or mortality, and with a 5-year survival greater than 20%.
Combined-Modality Treatment in the Adjuvant Setting
For patients who have undergone surgical resection, radiation and chemotherapy are often given in an attempt to prolong survival. A Gastrointestinal Tumor Study Group (GITSG) trial showed an improvement in median survival in those treated with fluorouracil (5-FU) and radiation vs observation after resection (20 vs 11 months). The median age of patients in this study was 64 years for those treated and 59 years for controls. No specific toxicities or benefits of treatment were reported for older patients. However, age was not a significant prognostic factor for survival; only initial performance status and extent of tumor were predictive of survival.
In another nonrandomized study, Yeo et al offered patients a choice between three adjuvant regimens: standard 5-FU/radiation, intensive 5-FU/radiation plus maintenance 5-FU, or no therapy. There were no differences between these groups in regard to sex, tumor characteristics, race, or intraoperative factors. However, patients receiving adjuvant therapy were younger than those observed. Patients who had longer postoperative stays and more complications were less likely to choose adjuvant therapy. It is not clear whether more of these patients were elderly. In multivariate analysis, only the size of the tumor, intraoperative blood loss, and use of adjuvant therapy were predictive of survival. More recent studies report that 5-FU given as a prolonged intravenous infusion is better tolerated and allows for greater dose intensity than bolus 5-FU in patients with advanced pancreatic cancer.
While most studies involving radiation include older patients, the specific toxicities and benefits of therapy for the elderly are not reported. Radiation therapy has been studied in elderly patients in other diseases, such as head and neck cancer, breast cancer, and prostate cancer.[31,32] In general, older patients tolerate radiation treatment as well as younger patients, although older patients being treated for bladder or rectal cancer may experience more toxicity.
There are very few data, however, on tolerance of abdominal radiation in elderly patients. In general, the toxicities of abdominal radiation include nausea, vomiting, diarrhea, and anorexia. Elderly patients may be more susceptible to dehydration, electrolyte disturbances, and infection, and may require multiple medications for symptom control while undergoing radiation therapy. Also, elderly patients often have problems with transportation, which makes completing therapy more difficult. Further investigations are needed to define the tolerance and benefit of radiation for pancreatic and other abdominal cancers in elderly patients.
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