SSAT - ADJUVANT CHEMOTHERAPY IN OLDER PATIENTS WITH LOCALLY ADVANCED COLON CANCER: IS LESS MORE?

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ADJUVANT CHEMOTHERAPY IN OLDER PATIENTS WITH LOCALLY ADVANCED COLON CANCER: IS LESS MORE?
Julia Frebault^*^1,2, Alexander Troester¹, Michael Horsey¹, Sarah Mott³, Schelomo Marmor¹, Arjun Gupta¹, Imran Hassan⁴, Pridvi Kandagatla⁵, Paolo Goffredo¹
¹University of Minnesota Twin Cities, Minneapolis, MN; ²Hennepin County Medical Center, Minneapolis, MN; ³University of Iowa Hospitals and Clinics, Iowa City, IA; ⁴MercyOne, Des Moines, IA; ⁵Allina Health, Minneapolis, MN

Introduction
Current national guidelines recommend adjuvant chemotherapy for patients with high-risk stage II and III colon cancer. However, the use of multi-agent chemotherapy (MAC) over single-agent chemotherapy (SAC) alone in the older population remains controversial, as additional agents may increase morbidity without substantial difference in prognosis. This study aimed to assess whether the survival benefit of SAC and MAC in patients with stage II and III colon cancers diminishes with age.

Methods
The National Cancer Database was queried for adults who underwent surgical resection for colon adenocarcinoma 2010-2020. Three groups were analyzed: 1. Low-risk Stage II (tumor stage (T) 3, no lymphovascular invasion (LVI) or perineural invasion (PNI), and well- or moderately-differentiated grade); 2. High-risk Stage II (T4, LVI, PNI, or poorly-differentiated grade); and 3. Stage III. Patients who received neoadjuvant chemotherapy or other systemic therapy were excluded. Multivariable Cox regression models with an interaction term were used to estimate the differential effect of adjuvant chemotherapy on overall survival (OS) by age (18-69, 70-79, and ?80 years).

Results
A total of 18,740 patients with low-risk stage II (6% received SAC and 5% MAC), 10,794 with high-risk stage II (15% received SAC and 18% MAC), and 32,427 with stage III cancer (12% received SAC and 65% MAC) were included. The majority of patients in each cohort were in the youngest age group. Five-year OS was 80% for low-risk stage II, 73% for high-risk stage II, and 70% for stage III cancers (Figure 1A, B, and C, respectively). On multivariable analysis, the effect of chemotherapy on OS did not significantly differ by age in any of the stage groups, evidenced by similar hazard ratios across age groups within the same chemotherapy comparison (Table 1). Irrespective of age, in the low-risk stage II group, neither SAC nor MAC provided a significant survival benefit when compared to observation alone (Table 1A). In the high-risk stage II group, SAC was associated with marginally improved survival compared to MAC (Table 1B), whereas in the stage III group, MAC was associated with better OS compared to SAC (Table 1C).

Conclusions
In this analysis of a national cohort of patients with locally advanced colon cancer, increasing age did not significantly impact the survival effect of adjuvant chemotherapy. In low-risk stage II cancer, adjuvant chemotherapy provided no additional benefit, while there was benefit of SAC over MAC in high-risk stage II, and MAC over SAC in stage III. These findings are in line with current guidelines, although de-escalating chemotherapy in node-positive disease may be detrimental in selected healthy older patients. This population benefits from an individual decision-making based on functional status, balancing oncologic outcomes with quality of life.

Table 1. Results comparing single-agent and multi-agent chemotherapy to no chemotherapy by age group from multivariable analysis of factors influencing mortality in patients with low-risk stage II (A), high-risk stage II (B), and stage III (C) colon adenocarcinoma.

Figure 1: Kaplan-Meier analysis demonstrating cumulative probability of mortality through 120 months post-operatively stratified by chemotherapy group (no chemotherapy, single-agent chemotherapy, and multi-agent chemotherapy) in patients diagnosed with A) Low-risk Stage II B) High-risk stage II, and C) Stage III colon adenocarcinoma, demonstrating decreased survival probability with time from surgery for each stage group, worse survival in patients who did not receive chemotherapy, and improved survival in patients who received multi-agent chemotherapy in stage III.

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