Treatment Utilization and Outcomes for Locally Advanced Rectal Cancer in Older Patients

Abstract

Importance: The number of older patients (80 years and older) diagnosed with locally advanced rectal cancer (LARC) is expected to increase. Although current guidelines recommend neoadjuvant chemoradiation therapy (NACRT) followed by resection, little is known about management and outcomes in this older population.

Objective: To assess the trends in management of older patients diagnosed with LARC who had a surgical resection.

Design, setting, and participants: Patients 80 years and older who had a surgical resection for LARC were identified in the 2004-2016 National Cancer Database. Patients were grouped based on therapy sequence: (1) surgery followed by adjuvant therapy (AT), ie, chemotherapy or radiation; (2) surgery alone; or (3) NACRT followed by surgical resection. Data were analyzed in May 2021.

Exposures: NACRT followed by surgery, and surgery with or without AT.

Main outcomes and measures: Overall survival (OS) was assessed using Kaplan-Meier analyses with inverse probability of treatment weighting (IPTW) and Cox proportional hazards regression were performed to examine the association of NACRT with the risk of death.

Results: Of 3868 patients with LARC who underwent surgical resection, 2042 (52.8%) were male, and the mean (SD) age was 83.4 (3.0) years. A total of 2273 (58.8%) received NACRT followed by surgical resection. Factors independently associated with NACRT were more recent diagnosis, age 80 to 85 years (vs 86 years and older), fewer comorbidities, larger tumors, and node-positive disease. The Kaplan-Meier analyses with IPTW showed that 3-year and 5-year OS for NACRT (3-year: 68.9%; 95% CI, 67.0-70.8; 5-year: 51.1%; 95% CI, 49.0-53.4) vs surgery with AT (3-year: 64.4%; 95% CI, 59.0-70.2; 5-year: 43.0%; 95% CI, 37.4-49.5) vs surgery alone (3-year: 55.8%; 95% CI, 52.0-60.0; 5-year: 34.7%; 95% CI, 30.8-39.0) was significantly different (P < .001). After adjusting for confounders, patients who received NACRT were more likely to undergo an R0 resection (adjusted odds ratio, 2.16; 95% CI, 1.62-2.88), which independently improved OS (P < .001). Moreover, receipt of NACRT was independently associated with a 25% decreased risk of death (adjusted hazard ratio, 0.75; 95% CI, 0.69-0.82) compared with alternative treatment sequences.

Conclusions and relevance: Approximately 40% of older patients with LARC did not receive the current standard of care. In this cohort, NACRT was associated with a higher likelihood of an R0 resection and improved OS. Clinicians should advocate for receipt of NACRT in older patients with LARC.

Figure 1.. Number and Percentage in the Utilization of Surgery Alone, Surgery With Adjuvant Therapy (AT), and Neoadjuvant Chemoradiation Therapy (NACRT) Among Patients With Locally Advanced Rectal Cancer Over Time

Figure 2.. Inverse Probability of Treatment–Weighted Kaplan-Meier Curves for the Comparisons of Overall Survival Between Neoadjuvant Chemoradiation Therapy (NACRT), Surgery With Adjuvant Therapy (AT), and Surgery Alone

Figure 3.. Multivariable Cox Proportional Hazards Regression Analyses

APR indicates abdominoperineal resection; AT, adjuvant therapy; CEA, carcinoembryonic antigen; cN, clinical node stage; CRM, circumferential resection margin; cT, clinical tumor stage; HR, hazard ratio; NACRT, neoadjuvant chemoradiation therapy; PNI, perineural invasion.