Elsevier

The Lancet Oncology

Volume 9, Issue 5, May 2008, Pages 494-501
The Lancet Oncology

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Controversies of total mesorectal excision for rectal cancer in elderly patients

https://doi.org/10.1016/S1470-2045(08)70129-3Get rights and content

Summary

The cornerstone of treatment for rectal cancer is resectional treatment according to the principles of total mesorectal excision (TME). However, population-based registries show that improvements in outcome after resectional treatment occur mainly in younger patients. Furthermore, 6-month postoperative mortality is significantly increased in elderly patients (≥75 years of age) compared with younger patients (<75 years of age). Several confounding factors, such as treatment-related complications and comorbidity, are thought to be responsible for these disappointing findings. Thus, major resectional treatment is not advantageous for all older patients with rectal cancer. However, the Dutch TME trial showed a good response to a short course of neoadjuvant radiotherapy in elderly patients. Biological responses to cancer treatment seem to change with age, and, therefore, individualised cancer treatments should be used that take into account the heterogeneity of ageing. For elderly patients who retain a good physical and mental condition, treatment that is given to younger patients is deemed appropriate, whereas for those with diminished physiological reserves and comorbid conditions, alternative treatments that keep surgical trauma to a minimum and optimise the use of radiotherapy might be more suitable.

Introduction

The effectiveness of surgery for rectal cancer (figure 1) in the elderly (≥75 years of age) can be measured by survival, postoperative morbidity and mortality, and the ability of the patient to regain the independence they had before surgery. The incidence of rectal cancer is highest at around 80 years of age. However the incidence of comorbidity, which renders the patient vulnerable to postoperative complications, is also highest after this age (figure 2).1, 2, 3

Population-based studies have shown that the prognosis of patients with rectal cancer has improved over the past few decades. The Danish Nationwide Cancer Registry, a population-based registry with almost complete ascertainment, showed that between 1977 and 1999, 5-year survival gradually improved in all age groups, with the biggest improvement seen in the period between 1977 and 1989. In elderly patients, 30-day and 6-month mortality decreased substantially over time. Better anaesthesia, improved health awareness leading to earlier stage diagnoses, less emergency procedures (surgery within 24 h after first onset of symptoms), improved access to health-care services, and greater availability of effective treatments were considered factors responsible for these findings.4 In the Netherlands, Dutch cancer registries also note an improvement in outcome after surgery for rectal cancer, which accelerated in the 1990s.5

An explanation for the improvement in the 1990s might be the introduction of total mesorectal excision (TME; figure 1), which has become the standard for resectional treatment. Heald and colleagues6 introduced this technique, in which the rectum is removed enveloped within its mesorectal fascia, and Quirke and co-workers7 provided the anatomical basis for this concept by showing that an uninvolved circumferential margin is the most important independent factor for avoiding local recurrence.

In the Netherlands, TME surgery was introduced as a result of a trial done in 1996 that compared TME surgery with and without a short course of preoperative radiotherapy (5 fractions of 5 Gy).8 On the basis of the findings of this trial, TME combined with preoperative radiotherapy was rapidly accepted as the standard treatment for rectal cancer. However, the mean age of the patients included in the trial was 63 years, and, although no upper age limit was used, there is concern that the elderly population was under-represented. In most population-based studies, the mean age of patients with rectal cancer is 70 years and the relative incidence increases with age, reaching a maximum at 80 years of age.9 Therefore, whether the findings of the TME trial are applicable to the elderly population is unclear.

Other reports of under-representation of the elderly in clinical trials also exist.10, 11 The opinion that geriatric patients do not tolerate cancer treatments well might be a reason for why they are not always included in prospective randomised studies. Other possible explanations are exclusion criteria for comorbidity, which is increasingly present in older patients, and the reluctance of investigators to include frail patients in such trials. Despite this issue, the findings from most studies are presented irrespective of participant age. The exclusion of older populations from these trials leaves important questions unanswered—ie, are biological behaviour and responsiveness to treatment independent from age; and how do cancer treatments interact with the vulnerability of ageing people? In this paper, we will address the above mentioned topics and propose alternatives for the treatment of elderly patients with rectal cancer.

Section snippets

Methods

Two datasets were used for our analyses: data from the Dutch TME study and data from the Dutch Comprehensive Cancer Centres (CCC) South and West combined. Both datasets have been published before.12, 13 However, for this review new, unpublished analyses have been done. In the TME study 1356 patients had curative resection (1126 patients aged <75 years and 230 patients aged ≥75 years). 99% of patients had complete follow-up. In this dataset, we focused on mortality in elderly patients. In the

Results

The combined cancer registries of the CCC South and West failed to show a beneficial effect of the use of TME surgery in elderly patients (figure 3). Table 1 provides the relative risk of dying of rectal cancer according to 3-year age groups compared with the general population, and shows that age is an independent risk factor. Therefore, the effectiveness of TME surgery for rectal cancer in the overall population cannot be simply derived from the findings of studies that involve a

Discussion

Rectal-cancer surgery is a major procedure, highlighted by the number of postoperative complications. The occurrence of complications is associated with a higher postoperative mortality, which, in elderly patients, persists for at least 6 months, compared with a few weeks after surgery in younger patients.

Table 2 presents the complications that occurred in elderly patients in the Dutch TME trial (unpublished), showing that elderly patients are liable to more complications than their younger

Conclusion

After major resectional treatment, elderly patients with rectal cancer have an increased 30-day and 6-month mortality compared with younger patients. Treatment-related mortality is an important competitive risk factor, which obscures the positive effect of modern rectal-cancer treatment in those aged 75 years and above. Easy and applicable physiological and clinical scoring systems have been developed and validated as instruments for the identification of those with a high operative risk.

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