The expanding role of surgery in metastatic disease: A modern perspective

This issue of SJS features a mini-theme on metastasis surgery, highlighting the evolving landscape of surgical treatment for metastatic cancer. Surgical treatment of metastatic cancer, long a topic of debate and evolving paradigms, is gaining attention with ever more efficient systemic therapies and as multidisciplinary cancer care advances. Historically, distant metastases were often considered defining terminal disease, with palliative intent dominating treatment strategies and surgery being only rarely recommended. The concept of oligometastatic disease, where limited metastatic burden may still permit curative approaches, has however reshaped this narrative. Improvements in imaging, molecular profiling, systemic therapies, and perioperative care have led to the rethinking of metastasectomy as part of an integrated treatment approach. Increasingly, surgical resection of metastatic lesions is being reconsidered not only as a palliative measure, but as potentially extending survival or even leading to cure in select patient populations. This mini-theme offers an update on the evolving role of surgery in treatment of metastatic cancer across various primary tumors and metastatic sites.

Janssen et al. ¹ provide a comprehensive narrative review examining the role of surgery for patients with metastatic melanoma in the context of immune checkpoint inhibitor (ICI) therapy. With the advent of ICIs, particularly anti-CTLA-4 and anti-PD-1 agents, systemic therapy has revolutionized melanoma care and improved outcomes dramatically. This initially led to a diminished role for surgery. The authors highlight a growing body of retrospective data suggesting surgical removal of residual disease, following a partial or complete response to ICIs, particularly when resulting in no evidence of disease, may optimize long-term outcomes. These findings emphasize the importance of integrating surgical strategies into multidisciplinary treatment planning and call for prospective studies to clarify optimal timing and patient selection for metastasis surgery in the personalized management of advanced melanoma.

Hansson et al. ² review the literature surrounding surgical resection of liver and lung metastases from breast cancer. This is an area with less consensus and more controversy than metastasectomy for colorectal or melanoma metastases. Systemic therapies for breast cancer have improved significantly over recent decades with treatment based on molecular subtypes of the primary tumor or metastasis. The role of metastasectomy however remains ill-defined due to the lack of prospective cohort studies and randomized controlled trials (RCTs). Hanson et al present data from retrospective studies and meta-analyses that nevertheless suggest a possible survival benefit and safety in carefully selected patients. They highlight the importance of individualized decision-making, particularly when systemic therapy has led to a favorable response or disease stabilization. Also in this setting, there is a need for prospective studies to better define surgical indications, with the authors emphasizing that metastasectomy should be considered within clinical trials or as part of a multidisciplinary approach in selected cases.

In their extensive review, Yaqub et al. ³ address the multimodal management of colorectal liver metastases (CRLM), that remain a major cause of cancer-related mortality in colorectal cancer (CRC). The authors discuss that surgical resection continues to be the cornerstone of potentially curative treatment for patients with resectable metastatic disease. With advances in systemic chemotherapy, perioperative protocols, imaging, and intraoperative techniques, the 5-year survival rates have improved significantly. Importantly, the review by Yaqub et al offers a practical framework aimed at clinicians outside hepatobiliary surgery field, thus putting together a tool for diagnostic evaluation, therapy planning, and multidisciplinary collaboration. Yaqub et al. furthermore emphasize the increasing relevance of personalized treatment strategies guided by molecular markers, and the need to tailor surgical decisions to tumor biology and patient factors. In line with this approach, Smedman et al. ⁴ assessed the willingness to pursue living donor liver transplantation (LDLT) for CRLM patients. Surveys conducted among next of kin and healthcare workers revealed strong support for donation, particularly if it could extend survival by 6–12 months, highlighting the importance of perceived survival benefit in donor decision-making.

In a combined single-center study and literature review, Røsok et al. ⁵ investigate surgical management of adrenal metastases, with a particular focus on CRC as the primary malignancy. While adrenal metastases are often associated with disseminated disease and poor prognosis, the authors demonstrate that selected patients with oligometastatic disease, especially those with solitary adrenal metastases from CRC, may benefit from surgical resection. Their experience indicates that surgery can achieve survival exceeding 3 years in some patients. The review highlights the need for thorough diagnostic evaluation, including imaging and biopsy, and a personalized treatment plan that integrates systemic therapies and surgical intervention. Røsok et al. advocate for a multidisciplinary approach to these complex cases and argue that on-going advancements in systemic therapy enhance the potential value of surgical strategies in managing metastatic CRC to the adrenals.

Finally, in an original study Dahlberg et al. ⁶ present data from a population-based cohort study analyzing outcomes in CRC patients with isolated pulmonary metastases. Drawing on the Swedish Colorectal Cancer Registry, they show that among 8457 patients treated with curative-intent CRC surgery, only 1.1% developed isolated lung metastases. Despite this rarity, curative treatment primarily by surgery was associated with a striking 5-year overall survival of 68%, compared to just 8% among those receiving palliative care. Multivariable analysis identified age, number of metastases, and their distribution as significant predictors of survival. This study provides real-world registry evidence that, in selected patients, pulmonary metastasectomy extends survival. RCTs are lacking but these findings indicate the important role of surgery for isolated lung metastases within a multidisciplinary framework.

In conclusion, the accumulating evidence from diverse malignancies and metastatic sites highlights an evolving and increasingly prominent role for metastasectomy in modern oncologic care. These recent contributions to the literature underscore that surgical resection is not a relic of pre-systemic therapy oncology but rather a dynamic and adaptable tool. As systemic therapies become more effective and targeted, they may render previously unresectable disease amenable to surgery and/or allow surgery to consolidate responses and achieve durable remissions. Selection criteria remain critical, and surgery is not appropriate for all patients with metastatic disease. Nevertheless, when applied thoughtfully in a multidisciplinary context, metastasectomy can be a key component of personalized cancer care.