Introduction
Colorectal cancer (CRC), which accounted for the second highest number of cancer deaths in Europe in 2018, presents in 15–30% of patients with metastasis at diagnosis. In initially localized disease 20–50% of patients will eventually develop metastasis, most frequently in the liver or lung [1, 2].
In these metastatic patients, oligometastatic disease (OMD) refers to the intermediate phase between localized disease and widespread metastatic cancer. In CRC, OMD is defined as having a controlled, optionally resected, primary tumor and 1–5 metastatic lesions in up to two organ sites, where all metastases must be safely treatable with local therapies [1]. These include surgical resection, stereotactic ablative body radiotherapy (SABR), thermal ablation (TA), including radiofrequency ablation (RFA), microwave ablation (MWA) and cryoablation (CA), or catheter-directed therapies (CDT) like selective internal radiotherapy (SIRT) and transarterial chemoembolization (TACE).
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Methods
This review is based on conducting a PubMed search using the terms “colorectal cancer”, “oligometastatic” and “local therapy”, the Metastatic Colorectal Cancer: ESMO Clinical Practice Guideline [1] and the Onkopedia guideline “Kolonkarzinom” by the Deutsche/Österreichische/Schweizerische Gesellschaften für Hämatologie und Onkologie [2].
Patient selection
Imaging using advanced techniques such as CT (computed tomography), MRI (magnetic resonance imaging), or PET (positron emission tomography) scans is presently the principal means of establishing OMD [5]. Emerging research also indicates that molecular profiling is becoming increasingly important in identifying patients who may benefit most from local therapies.
For optimizing treatment outcomes patient management and selection requires a multidisciplinary tumor board (MDT) decision which at least includes appropriate specialists from medical oncology, gastroenterology, colorectal, hepatobiliary and thoracic surgery, diagnostic and interventional radiology, pathology, and radiation oncology [3].
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Given the lack of clear standards, the variety of treatment modalities, institutional specializations and patient preferences, multidisciplinary management is vital for selecting the optimal treatment for each patient.
Surgical resection
Surgery remains the gold standard for the resection of metastases in OMD, particularly due to its aim to achieve complete R0 resection and, thus, to achieve curative outcomes. The rationale for surgical intervention lies in its ability to remove both the primary tumor and metastatic lesions, thereby, reducing the overall tumor burden and potentially leading to cure [3].
When dealing with colorectal liver metastases (CRLM), it has been shown that surgical resection can significantly improve long-term survival rates, with studies indicating 5‑year survival rates ranging from 34 to 58% in selected patients [1, 6]. But the optimal timing for surgery is a subject of ongoing debate. An international consensus panel recommends performing simultaneous surgery for minor liver resections, while more extensive procedures such as hemihepatectomies should be conducted separately [7]. Non-anatomic resections might be favored to preserve liver function and enable future surgical interventions, as they offer similar long-term survival benefits to anatomic resections [8].
However, the surgical paradigm for CRLM is being challenged by advancements in TA techniques, as evidenced by the COLLISION trial. This trial proposed that TA could provide comparable outcomes to surgical resection in patients with tumors less than 3 cm so that TA may serve as a standard of care for small-sized CRLM [9]. The trial was stopped at halftime for having met predefined stopping rules and findings indicate that TA is less affected by complications, shorten hospital stay, and improve local control, without compromising disease-free and overall survival [10]. As such, the evolving landscape of TA presents a significant challenge to surgery as the unequivocal gold standard.
Thermal ablation
The three primary techniques of thermal ablation (TA) include radiofrequency ablation (RFA), microwave ablation (MWA) and cryoablation (CA). While RFA delivers high-frequency electrical currents to induce thermal necrosis of tumor cells, MWA employs electromagnetic waves to produce tissue-heating effects. It can achieve higher temperatures more rapidly and is less susceptible to heat- or coldsink effects. In contrast, CA involves the application of extreme cold to destroy cancer cells.
Ablation techniques can achieve local control rates comparable to surgical resection and as such have been integrated into clinical guidelines, particularly in patients who are not surgical candidates due to comorbidities or the location of metastases [1, 2, 11, 12].
While the traditional and guideline-conform size limit for TA in any malignant liver disease is around 3 cm, the development of stereotactic radiofrequency ablation (sRFA) has expanded this range. Precise planning using three-dimensional (3D) navigation systems, accurate probe placement, and the planning of multiple needle trajectories allow for local curative treatment of larger liver tumors, potentially up to 5 cm or more in some cases [13‐16].
Catheter-directed therapies
Selective internal radiotherapy (SIRT) and transarterial chemoembolization (TACE), as catheter-directed therapies (CDT), can be options when metastases are confined to the liver. These therapies aim to deliver targeted treatment directly to the tumor while minimizing impact on surrounding healthy tissue. TACE has been a standard treatment for liver metastases, particularly in patients who are not candidates for surgical resection. The combination of TACE with systemic chemotherapy has been shown to yield favorable outcomes, although the comparative effectiveness of TACE versus SIRT remains a topic of ongoing research [1, 2].
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Stereotactic ablative body radiotherapy
Stereotactic ablative radiation therapy (SABR) as an advanced, noninvasive radiation technique that delivers high doses to small tumors with precision has emerged as a viable alternative for patients who are not surgical candidates, demonstrating promising oncologic outcomes and improved quality of life [1]. The SABR-COMET trial reinforced the role of ablative therapies, indicating that patients with oligometastatic cancers benefit from comprehensive local treatment strategies [4, 17].
The ongoing SABR-COMET-3 trial is enrolling patients with any solid tumor, aiming to assess the efficacy and safety of SABR in a broader patient population. Additionally, the SABR-COMET-10 trial is recruiting patients with 4–10 metastases to evaluate the effectiveness of SABR in managing a higher number of metastatic lesions [18, 19].
Systemic therapy
Integrating chemotherapy into the management of omCRC also seems critical. Evidence suggests that systemic chemotherapy in a neoadjuvant setting can play a pivotal role in eradicating micrometastatic disease and reducing the size of initially unresectable metastases, thus, offering curative options to patients who were initially considered inoperable and/or enhancing the effectiveness of local treatments [20, 21]. The combination of local and systemic therapies is increasingly viewed as a comprehensive approach to managing oligometastatic disease, with ongoing clinical trials further elucidating the optimal treatment strategies [20, 22, 23].
Conclusion
The management of oligometastatic colorectal cancer (omCRC) is increasingly focused on local treatment strategies that can significantly enhance survival outcomes. The integration of surgical resection, thermal ablation and catheter-directed therapies, as well as ablative radiotherapy, and the combination with systemic therapy are critical components of a multidisciplinary approach to optimize patient care. As research continues to elucidate the characteristics and treatment responses of oligometastatic disease, personalized strategies will likely emerge, further improving prognosis for the affected patients.
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Conflict of interest
A. Kupferthaler declares that he has no competing interests.
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