Beyond the Knife: The Evolving Nonsurgical Management of Oligometastatic Colorectal Cancer

Abstract

In patients with liver-limited oligometastatic disease, the goal of treatment can be curative intent. Historically, this was accomplished in patients presenting with upfront resectable disease. The availability of increasingly efficacious chemotherapy and biologic combinations with encouraging response rates led to the potential to convert unresectable disease to resectability. Beyond the backbone of surgery, we now have a portfolio of locoregional strategies to consider.From an interventional radiology perspective, the use of portal vein embolization can facilitate hypertrophy of the liver in anticipation of resection, thus converting unresectable disease to one amenable to a surgical approach with curative intent. Technological advances in liver-directed ablative therapies have afforded the possibility of eliminate radiographically evident disease with the hope for long-term disease control. Advanced radiotherapy techniques are further increasing the therapeutic options for patients with metastatic colorectal cancer. Improvements in external-beam radiotherapy over the past 2 decades include image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy, and proton-beam therapy. Finally, selective internal radiation therapy (SIRT) with microspheres labeled with the β-emitter Y enable targeted delivery of radiation to hepatic tumors. A coordinated multidisciplinary approach is required to integrate these nonsurgical adjuncts in an evidence-based manner to optimize outcomes for patients with potentially resectable metastatic disease. In this article, we summarize recent developments in systemic therapy, radiotherapy, and interventional liver-directed therapies that have changed the treatment landscape for patients with oligometastatic colorectal cancer.

Bevacizumab Does Not Inhibit the Formation of Liver Vessels and Liver Regeneration Following Major Hepatectomy: A Large Animal Model Study

“…It is usual in clinical practice to allow a therapy-free period between the administration of the final dose of biological therapy and a hepatectomy so as to reduce the in vivo 36: 1083-1094 (2022) toxicity of the agent and to avoid any negative effects on the regeneration of the liver. It is recommended that bevacizumab be withheld for 6 to 8 weeks before resection, thus respecting the 3-week half-life of this agent (26). Our experiment involved the administration of bevacizumab immediately prior to the surgical procedure.…”

Proton Beam Therapy in the Oligometastatic/Oligorecurrent Setting: Is There a Role? A Literature Review

“…The interim results of a phase I/II trial of 60 GyRBE in three fractions with SBPT suggest excellent local control outcomes not only with minimal toxicity, but also affording the option of subsequent courses for out-of-field liver recurrences [34]. In their literature review, Gill et al [35] referenced a phase II clinical trial of 89 patients with liver metastases of varying histological types (mostly colorectal carcinomas (CRCs)) [36] as a proof-ofconcept to show that PBT is remarkably well tolerated (i.e., no grade ≥ 3 toxicities reported) and effective even for oligometastases that are 6 cm or larger (the 1-and 3-year local control rates were 71.9% and 61.2%, respectively). In line with previous photon series, the strongest predictor of poor LC was mutation in KRAS, particularly when also associated with TP53 mutation [37].…”

Beyond the scalpel – mortality after liver surgery in patients with liver metastases – time to rethink the indications

“…Increasing options for liver surgery (such as ALPPS) and improved perioperative management in patients undergoing liver surgery should not lead to ‘over‐indication’ of major resections in patients with comorbidities or a limited chance of achieving long‐term disease‐free survival. In this regard, open and balanced discussions are mandatory, both in multidisciplinary teams and with patients regarding the risk–benefit ratio of major hepatic surgery and possible non‐ or minimally invasive local treatment alternatives such as radiofrequency ablation or stereotactic radiotherapy. Ultimately, randomized trials comparing different local treatment modalities or strategies in selected patient groups are eagerly awaited.…”