E113: Real-World Analysis of Patients Receiving Neoadjuvant Chemotherapy with and without Chemoradiation for Locally Advanced Rectal Cancer

The PROSPECT trial showed non-inferiority of neoadjuvant chemotherapy (NAC) with selective use of neoadjuvant chemoradiation (CRT) in comparison with standard CRT. However, the results of randomized trials are often difficult to reproduce with real-world data. We aimed to evaluate the association of neoadjuvant strategy with oncologic and survival outcomes among patients with locally advanced rectal adenocarcinoma in a national database.

Methods:

The National Cancer Database (2012–2019) was queried for patients with clinical T2N1, T3N0 and T3N1 rectal adenocarcinoma who underwent definitive resection. We excluded patients who received palliative-intent treatment. Patients were categorized by receiving neoadjuvant CRT alone, NAC alone, or NAC with subsequent CRT for a subset of patients who completed at least 3 months of NAC prior to CRT as identified by treatment start date. Mixed-effects logistic regression assessed the association between neoadjuvant strategy and pathologic complete response (PCR) and R0 resection. Kaplan-Meier methods and mixed-effects cox proportional hazard regression assessed the association of neoadjuvant strategy and overall survival (OS).

Results:

Of 24,340 patients, 22,111 (91%) received CRT, 1,053 (4%) received NAC alone, and 1,176 (5%) received NAC with CRT. Patients who received NAC or NAC with CRT were more likely to have stage III disease, private insurance, and be treated at an academic or high-volume facility (all p< 0.001). After adjustment, odds of an R0 resection were lower with NAC alone (OR 0.74; 95%CI 0.56-0.97), but no differences were seen between those with CRT alone and NAC with CRT. In comparison with CRT alone, odds of a PCR were lower for both NAC alone (OR 0.79; 95%CI 0.64-0.98) and NAC with CRT (OR 0.50; 95%CI 0.39-0.65). For OS, NAC with CRT was independently associated with improved OS (HR 0.73; 95%CI 0.60-0.90), with no differences between NAC alone and CRT alone. However, rates of adjuvant chemotherapy (AC) were low, with 26% of CRT alone, 47% of NAC and 6% of NAC with CRT receiving AC. In a subset of patients who received AC, no statistically significant differences were noted in OS between those with CRT alone, NAC alone, or NAC with CRT.

Conclusions:

Although patients with CRT alone had higher rates of PCR, NAC alone had similar OS and NAC with CRT showed improved OS. Real-world analyses highlight the benefits of a total neoadjuvant strategy. However, additional large-cohort studies are needed to evaluate the benefits of NAC versus CRT.