Managing the primary tumor in patients with rectal cancer and synchronous liver metastases: The role of organ preservation.

155 Background: Modern therapy can achieve a clinical complete response (cCR) of the primary tumor in the patients with rectal cancer (RC). However, use of a rectal organ preservation (OP) strategy for patients achieving cCR among patients who present with synchronous liver metastases (SLM) remains an area of active investigation. This study aimed to evaluate the outcomes of OP in patients with a cCR after liver first treatment sequencing for metastatic RC. Methods: Patients with RC and SLM who underwent liver-first approach at an NCI-designated Comprehensive Cancer Center from 1998-2024 were identified. Patients who achieved a cCR of the primary tumor were stratified with respect to whether the primary tumor was resected or managed nonoperatively via an OP strategy. A time benchmark of 12 weeks from the date of cCR was used to control for immortal time bias. Rates of local regrowth (LReg) in the rectum, local recurrence in the pelvis after rectal resection (LRec), and extrapelvic recurrence (DR) were modeled with cumulative incidence functions, and 3-year overall survival (OS) was compared between groups. Results: Among 217 patients identified, 48 (22.1%) patients achieved a cCR of the primary tumor. Among these patients, 8 patients (16.7%) demonstrated progression prior to the benchmark and were excluded from analyses. Of these, 5 patients demonstrated extrahepatic DR, 1 intrahepatic DR, and 2 LReg. An additional 3 patients (6.2%) underwent rectal resection following the benchmark date without documented evidence of LReg and were also excluded. Of the remaining 37 patients, 12 underwent rectal resection prior to the 12-week benchmark (32.4%) while 25 did not (67.6%). At a median follow-up of 36.9 months, 14 patients managed with an OP strategy experienced LReg (56.0%). Of these patients, 9 patients (64.3%) underwent salvage resection, with an R0 resection rate of 88.9%. None of these patients experienced post-salvage LRec, and LRec rate was also 0% among patients who underwent initial resection. The remainder of those who did not undergo salvage resection had developed prior DR at the time of LReg (4/5, 80%), with one patient electing to continue OP. Rates of DR as the initial site of disease progression were similar between groups (52.0% resection vs. 58.3% OP, p=0.892). 3-year OS rates were not significantly different between groups (100.0% resection vs. 82.5% OP, p=0.18). Conclusions: In patients with RC who have SLM, undergo liver-first approach, and achieve cCR, an OP strategy is associated with high rates of LReg but has high rate of successful salvage and is not associated with significant differences in DR or 3-year OS rate compared to primary tumor resection. An OP strategy for metastatic RC may be a feasible management strategy for select patients, with future work aimed at identifying patients with favorable tumor biology in whom this strategy would be most oncologically appropriate.