Treatment of colorectal cancer in patients aged over 75

European Journal of Surgical Oncology 1998; 24:391-395

Treatment of colorectal cancer in patients aged over 75 A. Shankar and I. Taylor

Department of Surgery, Royal Free and University College London School of Medicine

Colorectal cancer is a common malignancy which is occurring with increasing incidence in the elderly. As the age of the population increases so the importance of this malignancy will gradually increase. In addition a high proportion of elderly patients present with intestinal obstruction secondary to colorectal cancer and therefore the management of intestinal obstruction in the elderly becomes an important surgical consideration. This review discusses the management of colorectal cancer in patients over the age of 75 in both the elective and emergency situations with particular reference to screening, surgical management and the use of adjuvant therapy.

Ke.v words: colorectal cancer; elderly.

.Introduction Colorectal cancer is the second most common cause of cancer death anaongst western countries. It is predicted by the office of Population Census and Surveys in the UK that the overall population will remain static whilst the number of people aged 80 and above will rise by one-third in the next 15 years/Given that the incidence ofcolorectal cancer rises with age, these data have important implications with regard to health economics and resource allocation. Overall there has only been a marginal improvement in the survival of patients with colorectal cancer in all age groups, related primarily to improvements in post-operative mortality, with the 5-year survival rate remaining approximately 40%. Peri-operative mortality rates for the over-70 age group vary depending on the series studied, but improvements have been observed over earlier studies.-"4 These improvements in peri-operative care, coupled with safer surgery, have led to an increasing number of elderly patients undergoing more major procedures than previously. Patients in this age group are more likely to undergo emergency operations which is associated with a concomitant increase in peri-operative mortality and reduction in overall survival,s7 Given the increasing costs of care associated with elderly patients undergoing such procedures, the implications on health care economics will become crucial to future planning.

Incidence g

There has been a dramatic increase in the population aged over 75 in the last 20 years due to improvements in general Correspondence to: Professor 1. Taylor, Department of Surgery, UCL Medical School, Charles Bell House, 67-73 Riding House Street, London, WIP 7LD, UK. 0748-7983/98/050391+05 $12.00/0

healthJ This extended longevity has led to a redefining of old as being over the age of 70. When assessing the possible benefits of treatment it must be borne in mind that a 70year-old man can expect a further life expectancy of 8 years and a woman 13 years. Unfortunately, as age increases so does the risk of developing colorectal cancer, with an incidence of 20 per 100,000 in the under 65 group rising to 337 per 100,000 in the over 65 group) The pattern of disease in the elderly has altered slightly, becoming more proximal and hence harder to detect, ~-t° although this should lead to a reduced number of stomas being formed, especially in tile emergency situation.

Screening Given that 90-95% of colorectal cancers occur sporadically, screening in the older age group (who already have an increased risk of developing colorectal cancer compared to younger individuals) would appear to be of benefit. This is especially true for colorectal cancer where it is known that treatment of earlier disease improves prognosis. Since most colorectal cancers arise within precursor benign polyps" there is a long asymptomatic period, of approximately 5 years, prior to a carcinoma developing. This offers the opportunity to detect and treat colorectal cancer at an earlier stage. Since the symptoms of rectal bleeding and a change in bowel habit are often associated with more advanced disease, earlier detection at the asymptomatic stage becomes of paramount importance if survival is to be improved. For any form of screening to be effective the disease must be both common and have a well-understood natural history. Clearly colorectal cancer meets both these criteria. This is particularly important in the elderly, where late presentation, often as an emergency, carries a worse prognosis. © 1998W.B.SaundersCompanyLimited

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The ideal screening investigation, for any disease, should be accurate, acceptable to the patient and inexpensive. If a lesion is detected there needs to be rapid access to confirmatory investigations and institutions providing definitive management• Unfortunately all screening investigations that have been assessed to date with regard to colorectal cancer have several drawbacks. Faecal occult blood testing has been assessed in five controlled prospective trials, which included patients ranging in age from 45 to 80, who were asymptomatic, both biannually and annually. These trials demonstrated earlier detection of disease, compared to the unscreened group, and achieved improvements in mortality of up to 33% in the screened populationJ T M Faecal occult blood testing is, however, inaccurate and requires standardization of methodology in order to reproduce these results on a wider scale. Approximately 50% ofcolorectal cancers are diagnosable by a 60-cm flexible sigmoidoscope and results from two case-control studies suggest improvements in survival by 30--40%. j-''~5 The combination of annual faecal occult blood testing and flexible sigrnoidoscopy may improve results and overcome some of the limitations of each test individually. Unfortunately there are no randomized trials currently available which assess this screening combination. The main drawbacks to flexible sigmoidoscopy are patient compliance, cost and availability of trained practitioners. Maule t6 demonstrated that nurses trained to do flexible screening sigmoidoscopy are as accurate as gastroenterologists and might help to reduce the problem of cost and availability of practitioners. Screening with colonoscopy offers the advantage of viewing the entire colon, but has a number of important drawbacks. It requires sedation, there are risks associated with the procedure, it is expensive, is poorly tolerated and would make unacceptable demands upon already stretched facilities• One suggestion is to perform a single screening colonoscopy at age 60, the usefulness of which has not yet been assessed jT'~sby a randomized study. Studies in the USA suggest that combination of flexible sigmoidoscopy and faecal occult blood testing lead to estimated costs, per year of life saved, of $25,000, which they believe to be costeffective, t-' In summary, although screening might improve the prognosis in the elderly there are many problems which prevent its introduction both clinical and economical.

Surgical treatment of colorectal cancer

Resection offers the only hope of cure in patients with colorectal cancer and in the majority of those with incurable disease it is the best form of palliation. The key feature of most studies to date is that age alone is not a limiting factor in the surgical management of this disease, rather comorbidity and emergency surgery are confounding factors. Kingston et al., ~9in a study of 882 patients, demonstrated similar 5-year survival, morbidity and mortality rates for elderly patients undergoing curative surgery compared to younger patients. It is the patient's fitness rather than their

age which is the determining factor, i.e. their biological rather than their chronological age. Damhuis et al., 2° in a study of 6457 patients with colorectal cancer, demonstrated that even in patients aged over 80, acceptable morbidity and mortality rates could be achieved although resection rates were lower for patients aged over 89. Mulcahy et a l l ' in a study of 225 patients aged over 70, found that although these patients had a higher rate of emergency presentation compared to a younger age- and sex-matched group, those patients undergoing curative resection had similar survival rates. Fabre et al., 2~ in a study of 238 patients aged over 75 and operated on for colorectal cancer, found that it was the control of post-operative complications related to comorbidity that affected survival rather than the tumour characteristics. Similar results were reported by Arnaud et al., 2'- who demonstrated similar 5-year survival for patients aged above and below 80, if patients dying from nonmalignant disease were excluded. Some have suggested that these surprising survival rates for the elderly who survive surgery are due to less aggressive tumour biology,-'3although this is not confirmed in other studies. Hessman et al.. "-4 in a study of 202 patients aged over 75, reported that the American Society of Anaesthesiologists (ASA) score rather than age alone was a predictor of morbidity and mortality and those patients who underwent curative surgery had favourable 5-year-survival rates. Akoh et al., ~-5 in a similar study looking at patients aged over 80, again found that it was the ASA class rather than age which predicted morbidity and mortality, with similar 5-year survival rates compared to younger patients, provided they survived the post-operative period. Violi et al., "-6 in a study of 1256 patients operated on for colorectal cancer, divided patients into four age groups; <60, 60-69, 70-79 and >80. They found that the age-related survival curves for all four groups were similar once ageassociated causes of death were eliminated. Again the morbidity and mortality rates rose with age, as did the number of patients deemed unfit for curative surgery.

Emergency surgery Overall, approximately 20% of patients with colorectal cancer will present as an emergency. 3'27-29 Several studies suggest a poorer prognosis compared to elective surgeryJ '-'6'-'7This is especially important since the elderly have a higher incidence ofemergency presentation compared to younger patients. Anderson et al., 5 in a study of 645 patients, demonstrated that, in those older than 75 years, there Was a disproportionate incidence of emergency versus elective admissions. Waldron et al., ~° in a study of over 1000 patients with colorectal cancer, found that the elderly 01=522) were more likely to be admitted as an emergency. These elderly emergencies had significantly higher mortality than similar elective patients. Given that many elderly patients may have comorbid conditions, early identification and appropriate treatment of such problems will improve outcome. Studies suggest that cardiorespiratory pathology is more likely to cause

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problems than the actual surgery, 3~ with the age of the patient being less important. The management of an acute right-sided emergency is well established with either a right or extended right hemicolectomy remaining the treatment of choice) -''33 The management of acute left-sided lesions has become more controversial, with many units now utilizing primary resection and anastomosis with or without a defunctioning stoma as an alternative to a Hartmann's procedure. Since 1921, when Hartmann first described this technique, there have been modifications to the procedure, although the traditional three- and two-stage techniques are associated with considerable morbidity and mortality. u-~6 Although Hartmann's procedure is still associated with a relatively low mortality rate of between 2.6 and 90/0, 37.38 staged procedures do have inherent problems, especially for the elderly patient, with multiple hospital admissions and many patients never going on to stomal reversalfl ~-" For those that do proceed to reversal of the stoma the morbidity rates range from 5 to 57% and mortality from 0 to 340/o.43'~ Primary resection with on-table colonic lavage and anastomosis is becoming more common in patients with left-sided obstruction with and without perforation. The only contraindications for most groups are gross faecal contamination and "septic shock. Age is not a contraindication to this technique and does not appear to be an independent variable with regard to morbidity and mortality. Maddern et a l : 5 reported 40 patients with a mean age of 67 who underwent this technique (32 with covering colostomies) with similar morbidity and mortality rates to groups of similar patients managed by a Hartmann's procedure. Biondo et al. 46 reported 212 patients with acute left-sided pathology of which 63 were treated by on-table colonic lavage and primary resection and anastomosis with a clinical leak rate of only 5%. The Scotia study group 47 reported the results of a randomized trial comparing colonic lavage followed by segmental resection (n=44, median age 67) with subtotal colectomy (n =47, median age 73) and ileocolic anastomosis for malignant left-sided colonic lesions. There was no difference in mortality and morbidity between the two groups, with the segmental group reporting better longterm 'bowel' function. The importance of a suitably trained surgeon to perform this procedure is stressed in all the above studies if acceptable results are to be achieved. In summary, age is not an independent predictor of surgical outcome and should not influence surgical management in the elective or emergency situation. Particular attention should be paid to identification and treatment of comorbid conditions which might adversely affect outcome, since if a curative resection is undertaken and the patient survives the post-operative period, similar survival rates to those found in younger patients are obtained.

for adjuvant therapy. However, with increasing age the dose-related toxicity becomes unacceptable to many and . renders the treatments suboptimal. Since adjuvant therapy will only improve survival and quality of life in relatively few patients and is associated with significant complications, it is perceived to be of less use in the elderly. Newcombe and Carbone 48 looked at a cohort of women with newly diagnosed breast or colorectal cancer in an attempt to determine whether age affected'the type of treatment given. Those aged over 65 were less likely to receive or accept adjuvant therapy and less likely to be referred for a specialist opinion. This is in keeping with similar studies which suggest that the elderly are less likely to receive appropriate tests and adjuvant therapy, regardless of their general healthfl 5~ Adjuvant therapy in the form of 5-ftuorouracil (5-Fu) and levamisole or folinic acid is the most commonly used regimen in colorectal cancer and appears to improve survival, especially in Dukes C (UICC stage III) patients, s2-~ The question of chemotherapy in the elderly has been assessed in very few trials. Brower et a l ) s assessed the use ofadjuvant 5-FU and levamasole in three groups ofpatients; those aged less than 70; between 70 and 74, and older than 75. Those patients aged greater than 75 when compared with those aged less than 70 had higher rates of hospitalization (31% vs 4%), reduced early dose intensity (0.71 vs 0.84) and a higher drop-out rate (53% vs 35%). The use of prophylactic portal vein chemotherapy in patients undergoing resection of primary colorectal cancer without liver metastases might improve survival) 6 Given the relatively minimal incidence of complications associated with this technique, unrelated to the patient's age, its use may be more tolerated in the elderly. Advanced disease .The use of chemotherapy for advanced disease in the elderly is more questionable since the issue of quality of life becomes even more important. Few studies have addressed this issue. Scheithauer e t al. 57 randomized patients with advanced colorectal cancer to chemotherapy or palliative care only and demonstrated an objective improvement in symptoms in the treatment arm. In an attempt to improve access to chemotherapy, Falcone et a l f l assessed the use oforal doxifluridine, a fluoropyridine analogue which becomes converted to 5-FU, in a phase II trial involving elderly patients with metastatic colorectal cancer. This study demonstrated improved patient tolerance over systemic 5-FU with minimal side-effects, producing response rates up to 140. Allen-Mersh et al. ~9 demonstrated an improved quality of life in patients with colorectal liver metastases treated with hepatic arterial chemotherapy, although none of the studies performed to date have focused on the elderly as a separate group.

Adjuvant treatment Liver resection Given that up to 35% of patients with colorectal cancer are aged over 65 and at presentation may not be curable by surgery alone, the elderly would appear to be candidates

Appoximately 50% of patients undergoing resection of a colorectal cancer will develop liver metastases, of which

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5-10% will be resectable. 6° A number of studies have demonstrated improvements in survival in selected groups of patients undergoing liver resection. 6°-62 Such improvements in survival are only achievable if the mortality and morbidity of hepatic resection are kept low and as such should only be performed in specialist centres. Studies have suggested that the elderly tolerate resection poorly, 6~ ~ although more recent studies have demonstrated acceptable morbidity and mortality rates with similar survival to younger patientsY These results were obtained by excluding patients with ASA greater than III, and by having access to sophisticated intensive-care facilities in an experienced tertiary referral centre. Again it is the presence o f c o m o r b i d conditions, rather than age, which affects survival.

Conclusion

The increasing incidence of elderly patients presenting with colorectal cancer has important implications for both health economics and clinical practice. Units dealing with colorectal cancer will need to appreciate the problems associated with this patient population if acceptable morbidity and mortality rates are to be achieved. Whether or not screening is able to improve disease detection and perhaps influence the natural history remains to be seen and assessed within the context of further randomized control trials. With an increasing proportion of elderly patients the management of acute left-sided colonic lesions will require standardization. Increased use of intra-operative lavage and primary anastomosis may offer an alterfiative to Hartmann's procedure for many elderly patients, who might otherwise be left with a permanent stoma. Individual patient management should be based on an accurate assessment of the risks versus gains of treatment, with biological rather than chronological age influencing treatment. Increasing life expectancy coupled with data suggesting similar results to those achieved in younger patients should lead to more flexible treatment protocols for elderly patients with colorectal cancer.

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