GS01 - Resection with Incomplete Surgical Margins versus Palliative Chemotherapy for Locally Advanced Rectal Cancer

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Purpose/Background: The survival disadvantage of positive margins in locally advanced rectal cancer (LARC) is well known, but how it compares to palliative chemotherapy remains uncertain. This study explores the survival differences between patients with T4, N any, M0 rectal cancer who underwent surgical resection with positive margins and those who undergo palliative chemotherapy without surgical intervention.

Methods/Interventions: Adult patients with T4, any N, M0 rectal adenocarcinoma were identified in the 2004-2022 National Cancer Database. Patients receiving neoadjuvant chemoradiation, surgical resection with R0 margins, and systemic chemotherapy were considered Surgery-R0, while those receiving neoadjuvant chemoradiation, resection with R1/R2 margins, and systemic chemotherapy were categorized as Surgery-R1/R2. Individuals who were treated with palliative chemoradiation and systemic chemotherapy alone comprised Non-Surgery.

The primary outcome was overall survival at 1-, 3- , and 5- years following diagnosis. Survival was assessed using Kaplan-Meier and Royston-Parmar models. A restricted mean survival time (RMST) analysis was performed, where ΔRMST is the mean absolute difference in survival time.

Results/Outcomes: Of 13,473 patients, 7,963 (59%) comprised Surgery-R0, 1,264 (9%) Surgery-R1/R2, and 4,246 (32%) Non-Surgery. On average, and relative to Surgery-R0, the Non-Surgery cohort was older, of higher comorbidity burden, and presented with larger tumors.

The median duration of follow-up time was 3.3 years (1.9-5.5 years). The Surgery-R0 group demonstrated superior survival at 1, 3 and 5 years, compared to both Surgery-R1/R2 (1 Year: 97 vs 94%, log-rank P< 0.001; 3 Year: 84 vs 61%, log-rank P< 0.001; 5 Years: 70 vs 43%, log-rank P< 0.001) and Non-Surgery (1 Year: 82%, log-rank P< 0.001; 3 Years: 49%, log-rank P< 0.001; 5 Years: 35%, log-rank P< 0.001).

Following risk-adjustment, and with Surgery-R0 as reference, Surgery-R1/R2 and Non-Surgery were linked with significantly inferior survival at 3 (Surgery-R1/R2 HR 2.66, CI 2.26-3.13; Non-Surgery HR 3.52, CI 3.11-4.00) and 5-years (Surgery-R1/R2 HR 2.43, CI 2.12-2.79; Non-Surgery HR 2.94, CI 2.64-3.28).

Upon RMST analysis, and over 5 years of follow-up, receipt of surgery with R1/R2 margins was linked with a 10.24 month decrement in overall survival time, relative to surgery with R0 margins (ΔRMST -10.24 months, CI -12.01, -8.47). Similarly, no surgery was associated with a 11.78 month reduction in survival time, compared to surgery with R0 margins (ΔRMST -11.78 months, CI -12.65, -10.92). Further, no surgery was linked with a 3.03 month decrement in survival time, compared to surgery with R1/R2 margins (ΔRMST -3.03 months, CI -5.56, -0.50).

Conclusion/Discussion: Our findings reveal that among LARC patients, resection in the case of compromised surgical margins was still associated with a 3 month increase in survival time over 5 years, relative to palliative treatment alone. Future work is needed to improve outcomes for this cohort.