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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.

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Surgical Treatment: Evidence-Based and Problem-Oriented.

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Colorectal cancer

and .

Department of Surgery, Royal Free and Unoiversity College Medical School, University College London

It is predicted that over the next 15 years the overall population will remain static whilst the proportion of people over the age of 80 will rise by one third. Given that the incidence of colorectal cancer rises with age, this data will have important implications with regard to health economics and resource allocation.

Incidence

The incidence of colorectal cancer rises with age with a reported incidence of 20 per 100,000 in the under 65 group rising to 337 per 100,000 in the over 65 group, Mulcahy (1994).

There has been a dramatic increase in the population aged over 75 in the last 20 years due to improvements in general health. When deciding upon treatment it must be born in mind that a 70 year old man can expect a further life expectancy of 8 years and a woman 13 years.

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 treat- ment 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.

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 definitive management.

Unfortunately all screening investigations that have been assessed to date with regard to colorectal cancer have drawbacks. Faecal occult blood testing has been assessed in five controlled prospective trials, and included patients ranging in age from 45–80, who were asymptomatic. These trials demonstrated earlier detection of disease, compared to the unscreened group, and achieved improvements in mortality of up to 33% in the 0screened population Levin B (1996), Winawer (1995).

Faecal occult blood testing is, however, inaccurate and requires standardization of methodology in order to reproduce these results on a wider scale.

Approximately 50% of colorectal cancers are diagnosable by a 60 cm flexible sigmoidoscope and results from two case control studies suggest improvements in survival by 30–40%. The combination of annual faecal occult blood testing and flexible sigmoidoscopy 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 (1994) 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 by 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 cost effective.

Surgical treatment of colorectal cancer

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 postoperative mortality, with the 5 year survival rate remaining approximately 30–40%.

Older patients are more likely to undergo emergency operations which are associated with increased perioperative mortality and reduction in overall survival.

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.

Most studies suggest 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. (1995), in a study of 882 patients, demonstrated similar 5 year survival, morbidity and mortality rates for elderly patients undergoing curative surgery compared to younger age patients. It is the patients fitness rather than age which is the determining factor ie their biological rather than chronological age. Damhuis et al. (1996) 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 al. (1994)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. (1993) in a study of 238 patients aged over 75, operated on for colorectal cancer, found that it was the control of postoperative complications related to comorbidity that affected survival rather than the tumor characteristics. Similar results were reported by Arnaud et al. (1991) who demonstrated similar 5 year survival for patients aged above and below 80, if patients dying from non-malignant disease were excluded.

Hessman et al. (1997), 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 favorable 5 year survival rates. Akoh et al. (1994) 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. (1998) 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 age associated 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 with an associated poorer prognosis.

This is especially important since the elderly have a higher incidence of emergency presentation compared to younger patients. Anderson et al. (1992), in a study of 645 patients, demonstrated that in those greater than 75 years old, there was a disproportionate incidence of emergency versus elective admissions.

Waldren et al. (1986) in a study of over 1000 patients with colorectal cancer, found that the elderly (n = 522) were more likely to be admitted as an emergency. These elderly emergencies had significantly higher mortality than similar elective patients.

Complications are more often due to comorbid conditions rather than the actual surgery and should be actively identified and treated.

The management of the emergency presentations of right sided tumors is well established with either a right or extended right hemicolectomy remaining the treatment of choice.

The management of acute left sided lesions is more controversial with many units now utilising primary resection and anastamosis with or without a defunctioning stoma as an alternative to a Hartmans procedure.

Although Hartmans procedure is still associated with a relatively low mortality rate of between 2.6 and 9%, staged procedures do have inherent problems, especially for the elderly patient, with multiple hospital admissions and many patients never going onto stomal reversal.

For those that do proceed to reversal of the stoma the morbidity rates range from 5 to 57% and mortality from 0 to 34%.

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 is 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 al. (1995) 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 with a Hartmans procedure.

Biondo et al. (1997) reported 212 patients with acute left sided pathology of which 63 were treated by on table colonic lavage and primary resection and anastamosis with a clinical leak rate of only 5%.

The Scottia study group (1995) 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 long term ‘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.

Adjuvant treatment

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 for adjuvant therapy. However with increasing age the dose related toxicity becomes unacceptable to many and renders the treatments suboptimal. Given that 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 (1993) 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 health.

Adjuvant therapy in the form of 5 fluorouracil and folinic acid is the most commonly used regimen in colorectal cancer and appears to improve survival especially in Dukes C patients. The question of chemotherapy in the elderly has been assessed in very few trials. Brower et al. (1993) assessed the use of adjuvant 5FU and levamasole in three groups of patients; those aged less than 70, between 70–74 and older than 75. Those patients aged greater than 75 when compared with those aged less than 70 had higher rates of hospitalisation (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 appears to improve survival. Given the minimal incidence of complications associated with this technique, which are not related to the patients age, its use maybe 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 et al. (1993) 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 al. (1994) assessed the use of oral doxifluridine, a fluoropyridine analogue which becomes converted to 5FU, in a phase II trial involving elderly patients with metastatic colorectal cancer. This study demonstrated improved patient tolerance over systemic 5FU with minimal side effects, producing response rates of up to 14%.

Allen-Mersh et al. (1996) 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.

Liver resection

Approximately 50% of patients undergoing resection of a colorectal cancer will develop liver metastases of which 5–10% will be resectable.

A number of studies have demonstrated improvements in survival in selected groups of patients undergoing liver resection. 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 centers. Studies have suggested that the elderly tolerate liver resection poorly although more recent studies have demonstrated acceptable morbidity and mortality rates with similar survival to younger patients. These results were obtained by excluding patients with an ASA greater than III, having access to sophisticated intensive care facilities in an experienced tertiary referral center.

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 the increasing proportion of elderly patients the management of acute left sided colonic lesions will require standardization. Increased use of intraoperative lavage and primary anastomosis may offer an alternative to Hartmans 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.

References

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Copyright © 2001, W. Zuckschwerdt Verlag GmbH.
Bookshelf ID: NBK6898

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