LAUSR

e15500 Background: Anal squamous carcinoma accounts for 0.1% of global cancer cases, with rising incidence and mortality trends in the last decade. We want to demonstrate in this study that bulky lymph node involvement is associated with poor response and high recurrence rates. Limited data exist on this condition in the Latin American population. Methods: We retrospectively analyzed patients with anal squamous cell carcinoma treated with chemoradiotherapy (CRT) at the Instituto Nacional de Enfermedades Neoplásicas (INEN) from 2014 to 2020. Bulky N+ was defined as lymph nodes with a long-axis diameter ≥2 cm. A novel staging system was evaluated, categorizing bulky N+ as N2. Survival was analyzed using the Kaplan-Meier method, with differences assessed via the log-rank test. Results: 218 patients were included, median age 60 years (53 - 70), 83% female; 9.2% were HIV-positive, and 6.4% had unknown status. The most frequent clinical stages (AJCC 9th edition) were IIIA (27.1%), IIA (25.7%), and IIB (25.2%). Patients were classified as N0 (40.3%), non-bulky N+ (37.2%), or bulky N+ (22.5%). Median follow-up was 36 months (1–116). Overall survival (OS) at 12, 36, and 60 months was 92%, 59%, and 52%, respectively, median OS was 68 months. HIV-positive/unknown status increased the risk of death by 71% (HR = 1.71, 95% CI: 1.05–2.79), while ECOG 2–3 performance status had a 2.63-fold higher risk (HR = 2.63, 95% CI: 1.53–4.50). Patients without complete response (CR) after CRT had a significantly higher risk of death (HR = 6.87, 95% CI: 4.47–10.55). The recurrence progression-free survival (RPFS) rates at 12, 36, and 60 months were 89%, 78%, and 71%, respectively, with median RPFS not reached. Patients with bulky N+ had a higher risk of recurrence/progression (HR = 2.96, 95% CI: 1.52–5.77) and lower 5-year RPFS (36%, p < 0.001 ) and OS (33%, p = 0.002 ) compared to N0 or non-bulky N+ disease. Median OS for N0, non-bulky N+, and bulky N+ was 89, 56, and 32 months, respectively. The AJCC 9th staging system was not significantly associated with RPFS or OS (p = 0.55 and p = 0.23). A new staging system incorporating bulky N+ (N2 category) showed improved prognostic stratification, with 5-year RPFS and OS rates of 79% and 64% for stage I (T1-2/N0-1), 83% and 51% for stage II (T3-4/N0-1), and 36% and 33% for stage III (N2), respectively (p < 0.001 for RPFS; p = 0.0055 for OS). Median OS was 88, 68, and 32 months for stages I, II, and III, respectively. Median RPFS, reached only in stage III, was 40 months. Conclusions: Bulky lymph node involvement is a poor prognostic factor associated with worse outcomes, emphasizing the need for treatment intensification or incorporate new approaches that improve the results in these patients. Incorporating bulky nodal disease (N2) into the staging system enhances prognostic predictability and may guide future therapeutic strategies.