1041 - Durability of Watch-and-Wait after Long- vs. Short-Course Radiation In Total Neoadjuvant Therapy for Rectal Cancer
Presenter(s)
R. Ravella1, A. Bercz2, D. Nemorovsky3, E. K. Liu1, F. J. Arturi1, M. Reyngold1, A. J. Wu1, M. Widmar4, V. M. Williams1, M. Zinovoy1, L. Saltz5, P. Paty4, C. H. Crane1, M. Weiser4, D. A. Roth O’Brien1, J. Garcia-Aguilar4, A. Cercek5, M. Gönen3, J. J. Smith6, and P. B. Romesser1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Surgery, The Mount Sinai Hospital, New York, NY, 3Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 6Department of Colon and Rectal Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Watch-and-wait (WW) after clinical complete response (cCR) to total neoadjuvant therapy (TNT) enables organ preservation in locally advanced rectal cancer (LARC). Although long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) achieve similar cCR rates, the durability of organ preservation may differ. A COVID-era policy mandated a shift from LCCRT- to SCRT-based TNT at our institution, creating a natural experiment that minimized selection bias to test the hypothesis that LCCRT-based TNT yields more durable long-term organ preservation than SCRT-based TNT.
Materials/Methods: Consecutive patients with LARC treated with TNT from January 2018 to January 2021 at a single institution were included (LCCRT-based n=247; SCRT-based n=76). Response was assessed approximately 8 weeks post-TNT via clinical exam, endoscopy, and rectal MRI. Patients achieving cCR were offered WW. The primary endpoint was organ preservation; secondary endpoints included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). Organ preservation was defined as avoidance of TME (including local regrowth amenable to salvage by transanal excision), whereas local regrowth captured any pelvic tumor reappearance on WW surveillance following confirmation of cCR. Local regrowth amenable to salvage with an R0 TME was not considered to be a DFS event.
Results: Patient and tumor characteristics were similar between LCCRT and SCRT cohorts. Median follow-up was 72 months (95% CI 70-74) for LCCRT patients and 65 months (95% CI 63-67) for SCRT patients. cCR rates were comparable (44.5% LCCRT vs 43.4% SCRT). Five-year organ preservation among all treated patients was 37% (95% CI 31–43) after LCCRT vs 28% (95% CI 19–40) after SCRT (p=0.4). Among WW patients, five-year organ preservation was higher with LCCRT (83%, 95% CI 76–91) than SCRT (63%, 95% CI 48–82; absolute difference 20%; p=0.016). Five-year local regrowth was 22% (95% CI 14-30) with LCCRT vs 40% (95% CI 21-55) with SCRT (absolute difference 18%; p=0.028). Regrowth occurred earlier after SCRT than LCCRT, with 69% (9/13) vs 45% (12/25) of regrowth events arising within one year of cCR, respectively. Five-year distant recurrence (18% vs 16%; p=0.6), DFS (82% vs 84%; p=0.6), and OS (89% vs 94%; p=0.5) were similar for WW patients treated with LCCRT vs SCRT.
Conclusion: In a policy-driven natural experiment with nearly six years of follow-up, WW eligibility (cCR) was similar after LCCRT-based and SCRT-based TNT, but durable organ preservation favored LCCRT without differences in distant control or survival. Despite similar cCR rates, WW durability differed by radiation backbone. These data support LCCRT followed by consolidative chemotherapy as a preferred TNT strategy for patients pursuing organ preservation.