T103 - Rectal Cancer Watch & Wait Strategy: The U.S. Rectal Cancer Research Group Experience with 545 Patients

Purpose/Background: Watch and wait (WW) after neoadjuvant therapy (NAT) for clinical stage II or III rectal cancer is gaining acceptance in the United States (US). Data from the International Watch & Wait Database (IWWD) suggest acceptable rates of local regrowth (LRG), successful salvage when LRG occurs, and an association between LRG and distant metastases (DM). To date, similar data from a US consortium has not been reported. In 2022, the United States Rectal Cancer Research Group (US RCRG) was established to investigate practice patterns, and outcomes associated with WW in the US.

Methods/Interventions: This was a retrospective study of clinically staged II or III rectal cancer patients who underwent intentional WW after NAT, from January 2015 to August 2022. Data were collected by participating sites and entered in the US RCRG database. Variables included patient and tumor characteristics, NAT regimen, response assessment, LRG, salvage surgery, DM, disease-specific (DSS) and overall survival (OS). A cCR was defined as no evidence of residual cancer by clinical, endoscopic, or radiological examination, after NAT. Delayed cCR was defined as cCR that developed after the first NAT response assessment. LRG was defined as reappearance of tumor in the rectal wall, mesorectum, or lateral nodes during WW follow-up. Sustained cCR was defined as no LRG and no metastases during WW follow-up. Univariate and multivariate analyses were used to compare continuous and categorical outcomes. Kaplan Meier analyses were used to estimate 2-year LRG and DM rates and 3-year DSS and OS.

Results/Outcomes: 545 patients from 33 centers were included. Enrollment per center was 14 (IQR: 6–25) patients. Total NAT (TNT) with long-course CRT and consolidation or induction chemotherapy was used in 226 (41%) and 169 (31%), respectively. NAT with CRT only, TNT with short-course radiotherapy, or other regimens were used in 65 (12%), 57 (10%), and 28 (5%) respectively. Median interval to cCR after completion of NAT was 9 (IQR 6-12) weeks. Initial and delayed cCR occurred in 481 (88%) and 64 (12%) patients, respectively. Median follow-up was 21 (9-37) months. The estimated 2-year LRG rate was 18.3% (95 CI: 15.5-21.4%). The estimated 2-year DM incidence was 6.4% (95 CI: 4.7-8.6%). Among patients with or without LRG, DM were detected in 9.5% and 3.5%, respectively (P=0.013). Analysis of patient and tumor characteristics, NAT regimen, and initial or delayed cCR revealed no significant predictors of LRG. Salvage surgery for LRG was performed in 74/84 (88%) patients and included total mesorectal excision (TME) in 66 (89%) and transanal excision in 8 (11%) of patients. Surgical pathology was available for 59 salvage TME patients, of which 54 (91%) had R0 resections. Overall 3-year DSS was 96% (95% CI 92–98) and 3-year OS was 96% (91–98). For patients without LRG, the 3-year DSS was 100% and 3-year OS was 98% (90–99). For patients with LRG, the 3-year DSS was 85% (70–92) and 3-year OS was 84% (95% CI 69–92).

Conclusion/Discussion: In this US consortium experience with rectal cancer WW, our outcomes closely mirrored those of the IWWD and other international studies, with an expected incidence of LRG, most LRG amenable to curative resection, but increased DM and inferior DSS in patients with LRG. Our findings suggest that the growing adoption of WW in the US has occurred with acceptable oncologic outcomes, though further studies are required to confirm these findings, and more work is needed to identify the ideal patient for WW.