EP670 - Association Between the Sequence of Rectal Adenocarcinoma and Outcomes Following Neoadjuvant Chemoradiation and Proctectomy: An NCDB Study

Purpose/Background: Stage II-III rectal adenocarcinoma is typically treated with neoadjuvant chemoradiation (nCRT) followed by proctectomy. With advancements in cancer management, an increasing number of patients present with rectal cancer as a second primary malignancy. There is a paucity of data on how these patients differ from those presenting with rectal cancer as the sole primary cancer in terms of demographics, tumor biology, treatment patterns, and survival outcomes. We aimed to compare the features and outcomes of stage II–III rectal adenocarcinoma presenting as a sole versus second primary cancer.

Methods/Interventions: We conducted a retrospective cohort analysis of patients with clinical stage II-III rectal adenocarcinoma who underwent proctectomy following nCRT, who presented as either a sole or second primary malignancy. Data were obtained from the United States National Cancer Database from 2004-2020. Solo primary rectal cancer was defined as “one malignant or in situ primary only in the patient’s lifetime” and second primary as “second of two or more independent malignant or in situ primaries”. The primary outcome was 5-year overall survival (OS) and was assessed using Kaplan–Meier and multivariable Cox regression. Secondary outcomes included response to nCRT, conversion to open surgery, and short-term mortality

Results/Outcomes: Of 61,362 patients, 56,044 (91.3%) presented as a sole primary malignancy and 5318 (8.7%) as a second primary malignancy. The cohort had a mean age of 59 years, with 62.2% being male. Compared to patients presenting with a sole primary rectal cancer, patients with a second primary rectal cancer had significantly lower 5-year OS (69.4% vs 78.0%; p< 0.001) which was consisted among stage II (68.6% vs 76.3%; p< 0.001) and stage III disease (58.6% vs 67.4%; p< 0.001). On multivariable Cox regression, a second primary malignancy remained independently associated with increased mortality (aHR 1.26, 95% CI 1.12-1.42; p< 0.001). Other predictors of OS were increase age (aHR 1.03 per year), male sex (aHR 1.37, 1.27–1.49), higher T stage (aHR 3.62, 95% CI 2.39-5.48, p< 0.001), positive margins (aHR 1.75, 1.56-1.97), perineural (aHR 1.46, 1.32-1.62), lymphovascular invasion (aHR 1.35, 1.22-1.49), and increasing positive nodes (aHR 1.05 per node). Conversely, a minimally invasive approach (aHR 0.91, 0.84-0.98), low anterior resection (aHR 0.91, 0.83-0.99), urban residence (aHR 0.86, 0.78-0.96), Hispanic ethnicity (aHR 0.85, 0.71-0.99), and private insurance (aHR 0.75, 0.65-0.86) were associated with an increased OS.

Conclusion/Discussion: In patients with stage II–III rectal adenocarcinoma treated with nCRT and proctectomy, presentation as a second primary malignancy is associated with significantly lower 5-year OS than a sole primary. This effect remains after accounting for established prognostic factors, underscoring the need to incorporate prior malignancy status into risk stratification, counseling, and follow-up planning.