Outcomes in older people undergoing operative intervention for colorectal cancer

PURPOSE: To compare the outcomes of primary surgery for colorectal cancer i n an older patient population consisting of the young old (65-74), older ol d (75-84), and oldest old (greater than or equal to 85) with those in young er patient groups. BACKGROUND: Colorectal cancer continues to be a significant cause of cancer -related deaths in the United States, particularly in older people. Age rem ains the most significant risk factor for colorectal cancer.(1) Studies hav e shown that over 60% of patients requiring surgical intervention for this disease are age 70 and older.(2) Furthermore, for every 7 years over the ag e of 50, the risk of developing colorectal cancer nearly doubles.' The prev alence of colorectal cancer in older people is likely to increase further a s the size of the geriatric population increases. Surgical therapy is the cornerstone for treatment of colorectal cancer. Att empts at more conservative and less definitive treatment are associated wit h at least a twofold increase in death rate.(4) Given the propensity of old er people to develop colorectal cancer and the current status of surgery as the standard for treatment, the clinician is faced with the dilemma of how aggressive to be in treating this population of patients while being respe ctful of their coexisting comorbidities, life expectancy, and quality of li fe issues. Several studies have shown that age as an isolated factor has mi nimal or no effect on mortality after colorectal surgery for cancer.(5-9) T his systematic review analyzed postoperative mortality, morbidity, length o f hospital stay, overall survival, and cancer-specific survival as measures of outcome in older patients with colorectal cancer compared with younger (< 65 years) patients. DATA SOURCES: The following electronic databases were searched from when th ey were started to July 1998: Medline, Embase, CancerLit, Cochrane Controll ed Trials Register, Cinahl, Healthstar, Science Citation Index, Edina Biosi s, National Health Service Economic Evaluation Database, Index to scientifi c and technical proceedings, and Pascal. Manual searches were performed of conference abstracts from annual meetings of the Association of Surgeons of Great Britain and Ireland, European Congress of Surgery, American Society of Colon and Rectal Surgeons, 1996-1998, and the First European Conference on the Economics of Cancer, 1997. The National research register, Medical R esearch Council trials directory, current research in Britain, United Kingd om Coordinating Committee on Cancer Research trials register, center watch clinical trials listing, physician data query, Nation Institutes of Health inventory of clinical trials and studies, trial amnesty on Cochrane library , system for information on grey literature in Europe, index of UK theses, Department of Health and Social Services (DHSS) data CD, and the Internatio nal Network of Agencies for Health Technology Assessment (INAHTA) database were also searched for relevant citations and continuing or recently comple ted studies. Cancer registries in the United Kingdom in which prospective a udits were believed to have taken place were also contacted. STUDY SELECTION CRITERIA: Prospective, longitudinal studies of adults under going primary treatment for Duke's stage A-D colon or rectal cancer were el igible. Population-based studies (including all patients with colorectal ca ncer) and consecutive and nonconsecutive surgical series were included. Onl y those studies published after January 1, 1988, and with more than 100 par ticipants were included; studies in which patients without symptoms were id entified by screening and that focused on prognostic markers or blood trans fusion in relation to outcome of surgery and randomized controlled trials o f follow-up methods were excluded. DATA EXTRACTION: Data were collected from 28 independent studies, which inc luded 34,194 patients. These studies allowed for the data to be broken down by age. Three of the studies documented the progress of all patients with colorectal cancer within a geographical area, five documented data on all p atients presenting to the hospital irrespective of whether they underwent s urgery, and the remaining studies were prospective series of surgical cases (14 of which included consecutive patients undergoing surgery for colorect al cancer, six of which included only patients undergoing curative resectio n). Of the 28 studies, 22 included both colon cancer and rectal cancer pati ents, five included only rectal cancer patients, and one included only colo n cancer patients. Data were extracted by one reviewer from published papers and verified by a second reviewer. The following data were recorded: demographic characteris tics of patients, site and stage of the tumors, preoperative comorbidities, surgical interventions, and outcomes (including postoperative morbidity, m ortality, recurrence, survival, quality of life, and cost effectiveness). R ate ratios were calculated for each of the older patient subgroups with res pect to those patients less than age 65 for mortality and survival data. Po stoperative complications and prognostic factors, such as stage of disease and type of surgery (elective vs emergent) in different age groups, were co mpared by calculating an overall rate per group by summing the number of ev ents and the denominators from each individual study. The rates of postoper ative complications were then assessed for trends in incidence using the ch i-squared test, as were the distribution of prognostic factors. MAIN RESULTS: The study represented 34,194 patients, of which 34% were < 65 , 32% were 65 to 74, 27% were 75 to 84, and 8% were greater than or equal t o 85. The postoperative mortality rate ratios were 1.8, 3.2, and 6.2 in the 65 to 74, 75 to 84, and greater than or equal to 85 age groups, respective ly, when compared with the < 65 age group. The frequencies of various postoperative complications are shown in Table 1 . There was a significant trend toward increased rates of pneumonia/respira tory failure, cardiovascular complications, cerebrovascular accidents, and thromboembolism in older people, whereas rates of anastomotic leak were not significantly different. Table 2 shows the median 2-year and 5-year overall survival rates for each of the age groups. In those undergoing surgery with curative intent, the me dian survival rate ratios at 2 years were 0.92, 0.82, and 0.65 for the 65 t o 74, 75 to 84, and greater than or equal to 85 age groups, respectively, c ompared with those <65. However, this trend was not as clear as the trend i n overall survival secondary to the greater variability between studies. Data from consecutive patients presenting with colorectal cancer regardless of whether they underwent surgery suggested a decline in cancer-specific s urvival with age. However, cancer-specific survival in those undergoing cur ative surgery yielded rate ratios close to I at both 2 years and 5 years in all three older age groups. Median values for cancer-specific survival at 2-year and 5-year follow-up for those undergoing curative resection are sho wn in Table 3. A linear relation with respect to age and stage of disease at presentation (P = .0014) was evident in those who were staged, with older patients prese nting with more advanced disease. In addition, the frequency of unstaged ca ncers increased with age, with 3.9% in those <greater than>65, 6.1% in thos e 65 to 74, 9.0% in those 75 to 84, and 17.3% in those greater than or equa l to 85. Five studies reported data on prevalence of comorbidities. Several of the c omorbidities were more prevalent in the older age groups, but these comorbi dities were assessed differently in the various studies, and therefore pool ed estimates were not obtainable. There was a statistically significant (P < .0001) trend toward increasing r ates of emergent versus elective surgery with advancing age (Table 4). Ther e was also a significant trend toward decreasing rates of curative operatio ns with advancing age (P < .0001). The percentage of patients undergoing cu rative surgery were as follows: 76% in the <65 age group (n = 10,772), 75% in the 65 to 74 age group (n = 9,710), 73% in the 75 to 84 age group (n = 7 ,805), and 67% in the 85 age group ( n = 1,932). Data from studies reporting on the number of patients not undergoing surger y for colorectal cancer demonstrate that older people are less likely to un dergo surgery. The rates of no operation were 4%, 6%, 11%, and 21% in the < less than>65, 65 to 74, 75 to 84, and = 85 age groups, respectively. CONCLUSION: This systematic review concludes that the relationship between outcomes with colorectal cancer surgery and age of patients is complex and confounded by variables including stage at presentation, tumor site, preexi sting comorbidities, and type of treatment administered. Furthermore, selec ted older patients can achieve cancer-specific survival rivaling that in yo ung patients, as demonstrated by a relative cancer-specific survival of nea rly 1 for all older groups undergoing curative surgery. As such, surgery sh ould not be withheld from the older patient based on age alone.