Management of Colorectal Cancer in Older Adults
A retrospective study of 36 patients aged ≥ 70 years with rectal cancer evaluated the toxicity and feasibility of neoadjuvant 5-FU combined with pelvic radiation for treating locally advanced rectal cancer. Patients were classified as healthy and “fit” or “vulnerable” based on the presence of comorbidities.41 This study demonstrated that tolerability and response to neoadjuvant chemotherapy and radiation as well as ability to undergo surgery were similar in “vulnerable” patients and “fit” patients. Conversely, Margalit and colleagues studied the rate of treatment deviations in elderly patients with rectal cancer treated with combined modality therapy and found that most patients required early termination of treatment, treatment interruptions, or dose reductions.42 While trimodality treatment is the standard of care in rectal cancer, there is conflicting data from retrospective studies regarding the tolerability and feasibility of this approach. It is important to proceed with caution but to still consider fit older patients with locally advanced rectal cancer for neoadjuvant chemotherapy and radiation followed by surgery.
In patients who have a complete response (CR) to neoadjuvant chemoradiation, watchful waiting rather than proceeding to surgery may be a reasonable strategy, especially in older patients. A systematic review of 867 patients with locally advanced rectal cancer showed no statistically significant difference in OS between patients who were observed with watchful waiting and those who underwent surgery.43 The International Watch and Wait Database includes 679 patients who were managed with a watch-and-wait regimen because they had a clinical CR after chemoradiation. An outcomes analysis of these patients showed that 25% had local regrowth, with 3-year OS of 91% overall and 87% in patients with local regrowth.44 In most patients (84%), regrowth of the tumor occurred within the first 2 years of follow up.
In frail older adults, for whom longer courses of treatment are not feasible or chemotherapy is contraindicated, short-course radiation therapy can be considered either in the neoadjuvant setting or alone for palliation.45 A randomized trial of short-course radiation versus long-course chemoradiation in patients with T3 rectal cancer found that the difference in 3-year local recurrence rates was not statistically significant.46
Chemotherapy
An expected natural decline in function occurs with age, but given the great variability that exists between patients, it is important to focus on physiologic age rather than chronologic age to determine ability to receive and tolerate anticancer treatment. Decreases in renal and hepatic function, cognitive impairment, changes in gastrointestinal motility, decrements in cardiac and bone marrow reserves, as well as comorbidities and polypharmacy affect a patient’s ability to tolerate chemotherapy.47,48 Toxicity tools such as CARG and CRASH can help to predict severity of toxicity with chemotherapy.13,23 The information provided by these tools can help guide conversations between the oncologist and patient regarding treatment plans.
Adjuvant Chemotherapy for Early-Stage Disease
Stage II Disease
Defining treatment guidelines for older patients with stage II colon cancer is difficult due to lack of data that shows benefit in this population. The QUASAR (Quick and Simple and Reliable) group’s prospective study of adjuvant single-agent 5-FU in stage II colon cancer patients showed an absolute improvement in survival of 3.6% when 5-FU was given after surgery (95% CI 1.0 to 6.0).49 The subgroup analysis of patients aged ≥ 70 years showed a limited benefit of adjuvant 5-FU (hazard ratio [HR] 1.13 [95% CI 0.74 to 1.75]). Given the limited benefit, adjuvant 5-FU for elderly patients with stage II colon cancer should be used judiciously as patients may have competing causes of morbidity or mortality.
