Individualized Treatment Sequencing Selection Contributes to Optimized Survival in Patients with Rectal Cancer and Synchronous Liver Metastases.

Background: The optimal treatment sequence for patients with advanced rectal cancer and synchronous resectable liver metastases is controversial. We examined the outcomes associated with an individualized selection of classic, reversed, or combined approaches.

Methods: Between 1999 and 2014, 268 patients with rectal cancer and synchronous liver-only metastases underwent curative-intent multimodality therapy. Demographics and tumor and treatment details were reviewed. Survival outcomes were examined across treatment sequences and time periods (1999-2003, 2004-2008, and 2009-2014).

Results: Overall, 150 (56.0%) patients underwent primary tumor resection first ('classic' approach), 44 (16.4%) patients underwent simultaneous resection of the primary and liver metastases ('combined' approach), and 74 (27.6%) patients underwent liver resection first ('reversed' approach). Patients who underwent the reversed approach had more liver metastases (3 [2-5]) at presentation (vs. 1 [1-2.5] in the combined approach or 1 [1-3] in the classic approach; p < 0.001). Over time (from 1999 to 2003, to 2009 to 2014), both patients undergoing curative-intent treatment (62-122 patients) and the relative proportion of patients undergoing the reversed approach (6.4-37.7%) significantly increased. Despite higher disease burden, the 5-year overall survival (OS) was higher for patients treated in 2009-2014 versus those treated in 1999-2003 (76% vs. 45%; p < 0.002). Two hundred and ten patients (78%) were rendered free of disease; however, 58 were not due to disease progression or treatment complications, and their 5-year OS was poor at 6%.

Conclusions: Individualized selection of treatment sequence based on the liver metastases and primary tumor disease burden allowed most patients to complete resection of all gross disease, and is associated with a 5-year OS rate approaching that for stage III rectal cancer in the most recent era.