Notorious hallmarks of malignancy include the capacity to disseminate throughout the body, which is definitely undesirable and typically leads not only to the compromised life quality but also the shortened life span of the victims. From a traditional oncological perspective, it has usually meant that there had been, though not be discovered yet, already metastatic involvement of multiple sites or organs, once any systemic metastasis is detected. In this context, the role of metastasis-directed local therapy used to have quite limited importance [1,2]. However, in 1995, Hellman and Weichselbaum [3] raised an argument that there existed an intermediate state between localized and systemic disease, and first proposed the term “oligometastasis” and suggested that “some patients should be amenable to curative local therapeutic strategies.” Several attempts to administer local treatment to the patients with limited metastatic burdens have yielded more or less favorable outcomes. Notably, two studies on surgical resection of hepatic metastasis originating from colorectal cancer showed that a significant proportion of the patients could achieve long-term survival outcomes [4,5]. In addition, a larger retrospective study, which included over 5,000 patients with lung metastases from various primary sites, reported favorable 5-, 10-, and 15-year overall survival rates following complete lung metastasectomy, when compared to incomplete surgery (36%, 26%, and 22% vs. 13%, 7%, and 7%, respectively) [6]. Endorsed with these evidences, the perception of oligometastatic status emerged from the conceptual level to more realistic clinical category among the oncology communities [7,8]. Though supported by the evidences, the application of aggressive local treatment modalities to the patients with systemic metastasis used to encounter hesitancy and resistance by many cautious oncologists [9]. There have been many prospective trials, small and large, which evaluated the role of aggressive local treatment approaches, and most of them were in accordance to the fact that there is a certain role of local therapy in addition to the standard of care policy [10]. Moreover, there have been a few enthusiastic efforts to define and classify the oligometastatic status [8,11], but concrete and reliable guidelines on the definitions, diagnostic work-ups, and treatment strategies still remain to be determined.

Although local treatment has shown its efficacy in treating the oligometastatic patients, significant proportion of them ultimately have experienced progression of disease [10]. Consequently, the need for non-invasive ablative local treatment, as the alternative to surgical resection, has arisen. Modern radiation therapy (RT) techniques, such as stereotactic body radiotherapy (SBRT) and intensity-modulated radiotherapy, have enabled precise targeting of metastatic foci and reduced risk of toxicities by minimizing the bystander exposure to the normal organs. Many radiation oncologists have endeavored to explore the efficacy and suitable indications of local treatment for oligometastatic disease, and a few recently reported randomized studies confirmed that the consolidative local RT improved the oncologic outcomes in the oligometastatic patients [12-14]. This study is a survey-based research conducted by the K-OWG (Korean-Oligometastasis Working Group), a research group affiliated with the Korean Cancer Society, to investigate the perception of oligometastatic disease and treatment trends using the questionnaires to boardcertified radiation oncologists in Korea.

Online survey was performed from March to April 2022 and was distributed to the board-certified radiation oncologists, all of whom were the regular members of the Korean Society for Radiation Oncology (KOSRO). All respondents answered voluntarily, and the informed consent form was obtained from all of them. The questionnaires were developed and revised by seven radiation oncologists of the K-OWG committee. The survey consisted of four domains: five questions on the demographics of respondents; five on the definition of oligometastatic disease; four on the role of local therapy in treating oligometastatic disease; and four on the acknowledgment of the oligometastatic disease classification formulated by the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC), respectively (Table 1) [8]. The survey included both multiple choices and open questions. The Survey Monkey (Palo Alto, CA) platform was used, and this research was conducted according to the principles of the Declaration of Helsinki and locally applicable requirements.

Although it is generally agreeable that oligometastasis carries a better prognosis than polymetastatic disease, the biologic profile that can distinctively define oligometastatic status has not been established concretely [8,15]. Therefore, the definition of oligometastatsis is still based on the clinical perspectives. In the ESTRO-ASTRO consensus report, “up to 5” and “up to 3” oligometastatic lesions were the most commonly-used quantitative definitions, and the maximum number could be limited by the feasibility of curative metastasis-directed treatment [11]. In a similar context, 64% of physicians answered that they used “5 or less” as a quantitative definition for oligometastasis, and 26% answered that they used “3 or less” in the current study. Other response mentioned the feasibility of RT to include all disease burden.

According to the results based on the demographics, the radiation oncologists affiliated in the high-volume centers were more likely to be generous regarding the number of involved organs or tumor size, and they were also more familiar with the EORTC/ESTRO classification. Those with shorter career (practice years < 10) tended to have a stricter definition of oligometastatic disease, and they were more familiar with EORTC/ESTRO classification than more experienced counterparts. It could be because radiation oncologists with shorter career tend to follow guidelines while those with longer career tend to rely on their experience or institutional policies. Additional demographic analysis revealed that the radiation oncologists with 6-10 years of experience treated oligometastatic disease patients most frequently (S2 Table). Currently, the subspecialty of radiation oncologists was determined by the institutional circumstances or in-house rules, which were more likely based on where the cancer originated or spread. In order to stay up-to-date in this rapidly evolving situation, the designation of radiation oncologists who specialize in oligometastatic disease regardless of the origin, much or less similar to the surgical oncologist, who focus on the site to be managed, could be considered.

Local treatment for oligometastasis was expected to improve the oncologic outcomes by interfering the metastatic cascade progression or reducing the disease burden [15,16]. In particular, several recent randomized trials consistently reported that the additional local treatment significantly improved overall survival or progression-free survival (PFS) [12,13,17-19]. In line with these results, 82% of the respondents answered that they supported the role of local treatment in oligometastatic disease. In a systematic review conducted by the investigators [10], local consolidative treatment was associated with improved overall survival (odds ratio [OR], 2.896; 95% confidence interval [CI], 2.337 to 3.528) and PFS (OR, 3.045; 95% CI, 2.356 to 3.937). However, there was a difference in the benefit of local treatment by the primary cancer types. For example, in colorectal cancer, the OR associated with benefit of local treatment was 4.453 (95% CI, 2.103 to 9.429), whereas it was 1.043 (95% CI, 0.336 to 3.240) for small cell lung cancer, which was statistically insignificant [10]. Another systematic review on SBRT for oligometastases by Nevens et al. [20] also concluded that survival was most significantly influenced by the primary cancer type, where survival was the most favorable in prostate cancer and the worst in non-small cell lung cancer. Similarly, we found a minor difference in responses regarding the benefit of local treatment based on their respective specialties: 83% of the prostate cancer experts and 73.5% of the breast cancer specialists supported the benefit, respectively.

The term oligometastasis literally refers to the limited number of metastatic lesions. However, oligometastasis is a concept that might include a range of diseases including the synchronous disease in the early phase of metastatic cascade or that with small residuals after near-eradication by active systemic treatments. Therefore, the ESTRO-EORTC group classified oligometastatic disease into nine categories incorporating various factors including the disease-free interval, time of diagnosis, and previous treatment, respectively [8]. Although this classification was finely tuned to span over various clinical scenarios, 56% of the physicians in the current survey failed to adopt this classification into their clinical practice with the most common reason of “complexity.” Some respondents mentioned that it was difficult to use the classification in a multidisciplinary meeting, as there was disagreement among the caregivers, especially among non-radiation oncologists. Aforementioned recent systematic review reported that only 7.4% of the recruited oligometastasis studies (7 of 96) had sufficient information to apply full nine categories of EORTC/ESTRO classification [20]. Overall survival was not significantly different in comparison using three upper-level categorizations, among de novo, repeat, or induced oligometastasis. More intuitive and clinically applicable classification needs to be developed and verified. The studies are underway to decipher the biologic feature of oligometastasis by examining the profiles such as circulating tumor DNA or tumor cells, and these results are highly expected to add the robustness to the definition of oligometastasis [12,19].

Innate limitation of the current study is that this survey targeted only the radiation oncologists. In fact, with wider adaptation of metastases-directed conformal RT, oligometastasis has been of great interest among the radiation oncologists. However, systemic treatment remains as the mainstay modality for oligometastasis. Considering that less explored chemotherapy-free interval could be the potential key benefit to be achieved by adding local treatments, the viewpoint of medical oncologists is indeed crucial. In addition, this study was conducted without considering cancer primary and pathology. Further survey may be needed to exploit disease-specific queries according to cancer types and collect opinions from the subspecialists on more practical point of view.

While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Because oligometastasis encompasses a diverse range of diseases, clinically applicable classification and cancer-specific approaches need to be developed and verified. Continued education and training through multidisciplinary conferences on oligometastatic disease would be also required to build consensus among participating caregivers.