Role of stereotactic body radiotherapy (SBRT) for metastatic cancer patients beyond the traditional oligometastatic setting: a narrative review for an evolving concept

Introduction

The management of metastatic cancer has traditionally been dichotomized into curative intent for a limited disease and palliative systemic therapy for widespread metastases. However, this paradigm is evolving with the recognition that metastatic disease exists along a biological spectrum rather than as a binary state. The oligometastatic hypothesis, first proposed by Hellman and Weichselbaum in 1995, suggested that patients with a limited number of metastases (typically defined as ≤3–5 lesions) represent an intermediate state between localized and widely disseminated disease, potentially amenable to cure with aggressive local therapy (1).

The cutoff of ≤3–5 metastases for oligometastatic disease has lacked robust biological or clinical validation. The 2020 European Society for Radiotherapy and Oncology (ESTRO)-European Organization for Research and Treatment of Cancer (EORTC) consensus recognized that lesion count alone is insufficient to define oligometastatic disease and proposed a classification system based on biological and clinical processes rather than arbitrary numerical cutoffs (2).

This framework classifies oligometastatic disease into nine distinct states organized under three upper-level categories: de novo oligometastatic disease (first diagnosis without prior polymetastatic disease), repeat oligometastatic disease (recurrence after prior oligometastatic treatment), and induced oligometastatic disease (oligometastatic state achieved after systemic therapy for polymetastatic disease). These are further subclassified based on timing (synchronous vs. metachronous, using a 6-month threshold) and treatment context: oligorecurrence (progression during treatment-free interval), oligoprogression (limited progression on active systemic therapy), and oligopersistence (stable/responding disease on systemic therapy). Critically, the ESTRO-EORTC consensus explicitly stated that no definitive upper limit on the number of metastases can be established in the absence of validated biomarkers, provided the primary tumor is controlled and all sites are amenable to treatment. This position was reinforced by the ESTRO-American Society for Radiation Oncology (ASTRO) consensus, which emphasized that there are not yet adequate biomarkers—including number of metastases—to preclude a potential oligometastatic state.

Importantly, the number of metastases alone may be less important than other factors such as the number of organs involved, disease-free interval, performance status, and primary tumor characteristics and biology (3,4).

The prognostic validity of this classification has been confirmed in two independent validation studies. Baker et al. analyzed 381 patients from the SABR-5 trial and demonstrated that the ESTRO-EORTC classification independently predicted both progression-free survival (PFS) (P=0.005) and overall survival (OS) (P=0.002), with chronicity [synchronous presentation; hazard ratio (HR) 0.52, P=0.027] and oligoprogression (HR 2.05, P=0.004) being the strongest independent prognostic factors (5).

Willmann et al. evaluated 385 patients treated with SBRT and found that induced oligometastatic disease was associated with significantly shorter median OS (28.1 months) compared with de novo (46.3 months, P=0.002) and repeat oligometastatic disease (50.3 months, P=0.002) (6).

These studies confirm that biological context is more prognostically relevant than absolute metastasis count, a concept central to this review examining SBRT/SABR across the spectrum of metastatic disease states.

The growing population of patients diagnosed with oligometastatic disease is partly attributable to advances in imaging technology. The widespread adoption of more sensitive modalities—particularly prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) for prostate cancer and fluorodeoxyglucose (FDG)-PET/CT for other solid tumors—has led to significant stage migration, detecting metastases that would have remained occult on conventional imaging [computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy] (7).

This phenomenon has important implications: patients currently classified as oligometastatic using modern imaging may represent a biologically different population than those enrolled in earlier trials that relied on conventional staging, and the National Comprehensive Cancer Network (NCCN) guidelines now acknowledge that the number of metastatic sites defining oligometastatic disease is directly impacted by the sensitivity of the imaging used. The EORTC Imaging Group has emphasized the crucial role of standardized modern imaging to optimize the clinical diagnosis of oligometastatic disease and facilitate the design of metastasis-directed therapy (MDT) trials (8).

However, the traditional oligometastatic definition of ≤3–5 metastases have been increasingly questioned as arbitrary, and emerging evidence suggests that selected patients with more extensive metastatic burden may also benefit from stereotactic body radiotherapy (SBRT) (9-12).

SBRT also known as stereotactic ablative radiotherapy (SABR), has emerged as a precise, non-invasive ablative technique capable of delivering high doses of radiation in few fractions while minimizing exposure to surrounding normal tissues. The technique has demonstrated excellent local control rates and favorable toxicity profiles in treating metastatic disease across various cancer types (1,13).

Several reviews have addressed the role of SBRT in oligometastatic disease, including systematic reviews and meta-analyses evaluating safety and survival outcomes, consensus recommendations on the combination of SBRT with systemic therapies, appropriate use criteria for specific tumor types, and disease-specific summaries of clinical trial data. However, most of these reviews focus on the classical oligometastatic paradigm of ≤3–5 metastases and organize evidence primarily by tumor type or trial results. The present review takes a different approach by addressing the conceptual shift from a lesion-count-based to a biology-driven framework for patient selection, integrating evidence across the full spectrum of metastatic burden—from oligometastatic through polymetastatic to extensive polymetastatic disease (>10 lesions). In addition, this review uniquely synthesizes four thematic domains that are not typically addressed together: safety and efficacy stratified by metastatic burden, disease-specific biological heterogeneity, evolving treatment goals including quality of life (QoL) and symptom control, and the cost-benefit balance of advanced radiotherapy (RT) techniques in the palliative setting. This integrated perspective aims to provide a clinically useful framework for understanding the expanding role of SBRT/SABR beyond the traditional oligometastatic paradigm. We conducted a narrative review rather than a formal systematic review or meta-analysis, focusing specifically on the expanding role of SBRT/SABR as consolidative or ablative therapy in metastatic disease states that extend beyond the classical ≤3–5 metastasis definition. In this context, “beyond the traditional oligometastatic paradigm” refers to three interrelated clinical scenarios: (I) the treatment of patients with metastatic burdens exceeding the conventional oligometastatic cutoff, including polymetastatic disease; (II) the use of SBRT to treat oligoprogressive lesions during active systemic therapy, aiming to prolong the efficacy of the current treatment line; and (III) the integration of SBRT as part of a biology-driven, individualized treatment strategy in which patient selection is guided by tumor biology, disease dynamics, and clinical context rather than by lesion count alone. While SBRT is also used for other purposes such as reirradiation, toxicity reduction compared with conventional techniques, or treatment of radioresistant histologies, these indications fall outside the primary scope of this review unless they overlap with the clinical scenarios described above. Studies were selected based on methodological quality and relevance to this conceptual framework, with particular attention to prospective trials, patterns of failure, integration with systemic therapy, and patient selection criteria. We present this article in accordance with the Narrative Review reporting checklist (available at https://apm.amegroups.com/article/view/10.21037/apm-2026-0030/rc).

Methods

The aim of this review was to summarize the available evidence and discuss emerging clinical scenarios in which SBRT/SABR may play a role beyond the traditional oligometastatic paradigm. To explore how SBRT/SABR is being applied in metastatic cancer beyond the traditional oligometastatic framework, a structured search of PubMed/MEDLINE was carried out for studies published between January 2000 and December 2025. The search combined MeSH terms and free text keywords related to stereotactic radiotherapy (SRT) and evolving metastatic states, and additional studies were identified through manual screening of reference lists (Table 1).

Studies selection

Studies were eligible if they were randomized trials, prospective cohorts, or retrospective analyses evaluating SBRT/SABR in settings such as oligoprogressive disease or other emerging metastatic patterns. Publications that did not directly address these scenarios, including reviews, commentaries, case reports, and preclinical studies, were excluded.

Due to the significant heterogeneity in study designs and definitions within this field, the evidence was synthesized as a narrative review rather than a systematic review or meta analysis. Study selection emphasized methodological rigor and relevance to the review objectives, with the goal of offering an integrated overview of current data and emerging concepts on the use of SBRT/SABR in these expanding metastatic contexts.

To enhance transparency in study selection, a simplified flow diagram adapted from the PRISMA framework has been included (Figure 1), documenting the screening and selection process. Although a formal PRISMA-guided systematic review was not undertaken given the narrative scope of this work, the flow diagram provides a structured overview of how the final set of studies was identified.

Figure 1 Simplified flow diagram of study identification and selection process. SABR, stereotactic ablative radiotherapy; SBRT, stereotactic body radiotherapy.

The initial database search of PubMed/MEDLINE yielded 1,247 records. After removal of 183 duplicates, 1,064 unique records underwent title and abstract screening. Of these, 872 were excluded for the following reasons: not addressing SBRT/SABR in the metastatic setting (n=514), publication type not meeting inclusion criteria (reviews, editorials, commentaries, case reports, or preclinical studies; n=289), and non-English language publications (n=69). The remaining 192 articles underwent full-text assessment for eligibility. At this stage, 137 articles were excluded: 68 did not specifically address clinical scenarios beyond the traditional oligometastatic definition, 41 were duplicative in scope or reported overlapping patient cohorts with larger or more recent publications, and 28 had insufficient methodological quality or lacked relevant outcome data. An additional 12 studies were identified through manual screening of reference lists of included articles and relevant reviews. In total, 67 studies were included in the final narrative synthesis.

Review selection

A narrative review format was chosen over a formal systematic review or meta-analysis for several methodological reasons. The field of SBRT beyond the traditional oligometastatic setting is characterized by substantial heterogeneity in study designs, patient populations, disease definitions, endpoints, and tumor types, which would limit the feasibility and interpretability of quantitative synthesis. Systematic reviews in advanced cancer frequently demonstrate critically low methodological quality, particularly when heterogeneity is inadequately addressed. Furthermore, the primary aim of this work is to provide a conceptual framework for understanding the evolving role of SBRT across a spectrum of metastatic disease states, rather than to answer a single narrowly defined clinical question, a goal for which narrative reviews serve a distinct and complementary role in the literature. The evidence in this field is also rapidly evolving, with multiple ongoing phase III trials (SABR-COMET-3, SABR-COMET-10, SABR-SYNC) whose results will substantially reshape the evidence landscape. Nevertheless, to enhance methodological transparency, a simplified flow diagram of the study selection process has been provided (Figure 1), the level of evidence for each study is explicitly stated throughout the text, and the review follows the principles of the Scale for the Assessment of Narrative Review Articles (SANRA). These limitations should be considered when interpreting the findings and conclusions of this review.

When reporting study outcomes, endpoints are presented in the following hierarchy: OS, PFS (or systemic therapy-free survival where applicable), local control, toxicity, and QoL/patient-reported outcomes. This hierarchy reflects the relative clinical importance of each endpoint, although we acknowledge that in the palliative and polymetastatic settings, QoL and symptom control may be of equal or greater relevance to patients than survival endpoints.

Results

The results of this review are organized around four thematic domains that directly correspond to the research questions outlined above: (I) safety and efficacy data stratified by metastatic burden; (II) disease-specific outcomes and biological heterogeneity; (III) evolving therapeutic goals of SBRT, including QoL and symptom control; and (IV) cost-benefit considerations. These domains are examined separately, although not independently, and together provide an integrated framework for understanding the expanding role of SBRT/SABR in metastatic disease management. Throughout, the level of evidence supporting each finding is explicitly stated to allow the reader to distinguish between established evidence from randomized trials and exploratory data from phase I or retrospective studies. This structured approach reflects the growing complexity of metastatic disease management and highlights the expanding conceptual framework within which SABR is currently being explored. Ultimately, this framework helps address one of the key challenges in the expanding use of SBRT/SABR beyond the classical oligometastatic paradigm: the identification of patients most likely to benefit from local ablative therapy within increasingly complex metastatic disease states.

Safety and efficacy data

Treatment of 1–5 lesions

NRG-BR001 phase I trial established the safety of SBRT for patients with 3–4 metastases. This multi-institutional study enrolled 35 evaluable patients with breast, prostate, or non-small cell lung cancer (NSCLC), treating a median of 3 metastases per patient across seven anatomic locations. No dose-limiting toxicities or grade 5 adverse events occurred, with 8 grade 3 adverse events occurring 125–556 days after SBRT. The study established recommended SBRT doses: 30 Gy in 3 fractions for bone/spine metastases, 45 Gy in 3 fractions for peripheral lung/liver/abdominal-pelvic metastases and 50 Gy in 5 fractions for central lung and mediastinal lymph nodes (1).

The COMET trial, formally known as SABR-COMET, was a multicenter, randomized phase II study evaluating the impact of SBRT in patients with oligometastatic cancer. The trial enrolled patients with a controlled primary tumor and 1 to 5 metastases, with all metastases amenable to SBRT. The average number of metastases per patient was not explicitly stated, but the inclusion criteria capped the number at five, and most patients had fewer than five metastases. The objective of the trial was to determine whether adding SBRT to standard of care (SOC) palliative treatments improves OS in patients with oligometastatic disease. Secondary endpoints included PFS, toxicity, QoL, and the need for further systemic therapy. Results showed that SBRT significantly improved OS and PFS. The 5-year OS rate was 42.3% in the SBRT arm versus 17.7% in the control arm (P=0.006), and the 5-year PFS rate was 17.3% versus 3.2% (P=0.001). Long-term follow-up confirmed durable benefits, with 8-year OS of 27.2% in the SBRT arm versus 13.6% in the control arm. Toxicity rates were higher in the SBRT group; however, QoL was similar between groups (14-16).

Several important limitations of the SABR-COMET trial should be acknowledged. The study enrolled only 99 patients in a 1:2 randomization, resulting in 33 patients in the control arm and 66 in the SBRT arm—a sample size that limits the robustness of the findings. The trial included a heterogeneous mix of primary tumor types, making it difficult to determine which histologies drive the observed benefit. Three treatment-related deaths (4.5%) occurred in the SBRT arm, including one fatal radiation pneumonitis and one pulmonary abscess, raising important safety considerations. The open-label design may have influenced subsequent treatment decisions. Finally, this remains a phase II trial, and the ongoing SABR-COMET-3 phase III trial is needed to confirm whether the survival benefit is reproducible in a larger, more homogeneous population. Until phase III results are available, the SABR-COMET findings, while encouraging, should be considered hypothesis-generating rather than practice-defining.

The SABR-5 trial further validated safety in treating up to 5 oligometastases, enrolling 380 patients across six cancer centers. With median follow-up of 64.6 months, the study demonstrated excellent outcomes: median OS of 64.6 months, 5-year OS of 58.6%, and 5-year local control of 85.1%. Grade 3–4 toxicity occurred in only 9% of patients, with no grade 5 toxicity reported. These results established that treating up to 5 metastases with SBRT is safe and associated with meaningful survival benefits in appropriately selected patients (17,18).

SBRT is now considered a consolidative option for patients with oligometastatic cancer, particularly when all lesions are technically treatable and the primary tumor is controlled. In addition, there are ongoing trials focused on this setting of patients, highlighting the SABR-COMET-3 (NCT03862911) (19). It is a randomized phase III trial enrolling patients with 1–3 metastases from any solid tumor, comparing SOC versus SOC plus SBRT to all metastatic sites. The primary endpoint is OS, with secondary endpoints including PFS, toxicity, and QoL. This trial aims to confirm whether the survival benefit observed in the phase II SABR-COMET trial extends to a larger, more homogeneous population and to clarify the impact across different histologies.

Treatment of 5–10 metastases

Polymetastatic disease, typically defined as >5–10 metastases, has historically been considered suitable only for systemic therapy with palliative RT reserved for symptomatic sites (9).

However, technological advances in SBRT delivery, improved systemic therapies prolonging survival, and better understanding of metastatic heterogeneity have created a rationale for comprehensive ablative therapy even in multiple metastases (10,11).

The ongoing SABR-COMET-10 (NCT03721341) trial is a phase 3 randomized trial that is evaluating SBRT for patients with 4–10 oligometastases, extending beyond the traditional 3–5 metastasis cutoff. This trial will provide critical phase 3 evidence on whether comprehensive ablation of more extensive oligometastatic disease improves OS (14).

Rather than treating only symptomatic lesions, the approach aims to ablate all visible disease with the goals of: delaying disease progression; extending the efficacy of current systemic therapy, deferring or avoiding more toxic systemic treatments, and potentially achieving long-term disease control in selected patients with indolent biology.

Likewise, SABR-SYNC is an ongoing phase III randomized trial evaluating SABR in patients with synchronous oligometastatic disease with an untreated primary tumor, whereas SABR-COMET, SABR-COMET-3, and SABR-COMET-10 focus on metachronous disease or patients with controlled primary tumors. This distinction is clinically important because synchronous oligometastatic disease may represent different tumor biology and require different treatment strategies, including coordination of treatment to both the primary tumor and metastatic sites. SABR-SYNC will randomize 180 patients in a 1:2 ratio between SOC palliative-intent treatments alone versus SOC plus ablative therapy (SABR preferred) to all sites of known disease (12).

Treatment of >10 metastases

The application of SBRT to 10 or more metastatic lesions remains largely unexplored and should be considered investigational. The contemporary approach to specific tumor entities has evolved beyond simply counting metastases, now incorporating total disease burden and tumor biology into treatment decision-making. However, the evidence base for comprehensive ablation of extensive polymetastatic disease is extremely limited.

The Ablative Radiation Therapy to Restrain Everything Safely Treatable (ARREST) trial represents the only prospective study specifically designed to evaluate SBRT for polymetastatic disease defined as >10 metastases. This was a phase I dose-escalation study—designed to assess safety and determine the maximum tolerated dose, not to evaluate efficacy—that enrolled only 13 patients who had exhausted or refused standard systemic therapy, treating a total of 207 lesions. SBRT was delivered as weekly fractions of 6 Gy, escalating from 12 Gy (2 fractions) to 30 Gy (5 fractions). The trial demonstrated preliminary safety: acute toxicity was predominantly grade 1 (46%) or grade 2 (15%), with only 1 patient (7.7%) experiencing grade 3 neutropenia and no grade 4–5 toxicities or dose-limiting toxicities observed. QoL assessments showed modest declines at 6 weeks (P=0.009 for FACT-G). With median follow-up of 8.7 months, median OS was 13.8 months with 12-month survival of 62%; however, these survival figures should be interpreted with extreme caution given the very small sample size, absence of a control arm, and inherent selection bias of a phase I population. The study’s guiding principles—strict adherence to dose constraints, minimization of treatment burden, and prioritization of safety—proved effective in enabling comprehensive treatment of extensive disease from a technical standpoint.

These results should be regarded as exploratory and hypothesis-generating only. They demonstrate that comprehensive SBRT for extensive polymetastatic disease is technically feasible and does not appear to cause unacceptable acute toxicity, but they provide no evidence regarding clinical efficacy, survival benefit, or superiority over standard palliative approaches. Larger prospective studies with appropriate control arms are needed before any conclusions about clinical benefit can be drawn in this population (11,20).

Disease-specific outcomes and biological heterogeneity

The evidence suggests that it is not so much the number of lesions that matters, but rather the tumor entity, biology, synchronous vs. metachronous metastases, and molecular expression in terms of prognostic value. In fact, emerging evidence suggests that the number of organs involved may be more prognostically significant than the absolute number of metastases. Patients with metastases confined to 1–2 organs appear to have better outcomes than those with the same number of metastases distributed across multiple organs, suggesting that organ tropism reflects underlying tumor biology. In fact, a clinical prognostic model for OS in patients with extracranial oligometastatic disease (OMD) treated with SBRT has been developed and validated (21).

The ESTRO-EORTC classification provides a framework for interpreting these disease-specific differences: the distinction between de novo, repeat, and induced oligometastatic disease, and subclassification into oligorecurrence, oligoprogression, and oligopersistence, helps explain why the same number of metastases may carry different prognostic implications depending on clinical scenario and tumor biology.

Below, a summary of the evidence supporting the use of SBRT in metastatic patients according to primary tumor. A table (Table 2) summarizing the pivotal SBRT studies has been added.

NSCLC

The CURB trial demonstrated significant benefit for oligoprogressive NSCLC, with median PFS of 10 months with SBRT versus 2.2 months with SOC alone (HR 0.41, P=0.0039). This represents a more than four-fold improvement in PFS, suggesting that disease biology in NSCLC is particularly amenable to local ablation of progressive sites(22).

Breast cancer

In contrast to NSCLC, the CURB trial showed no benefit for oligoprogressive breast cancer (median PFS 4.4 vs. 4.2 months, P=0.43) (22).

Similarly, the NRG-BR002 trial failed to demonstrate survival benefit in oligometastatic breast cancer (24).

The available evidence does not support a benefit of SBRT in oligometastatic or oligoprogressive breast cancer. In the CURB trial, SBRT showed no improvement in PFS for oligoprogressive breast cancer (median PFS 4.4 vs. 4.2 months, HR 0.80, P=0.43), in stark contrast to the significant benefit observed in NSCLC within the same trial. Similarly, the NRG-BR002 trial failed to demonstrate any PFS or OS benefit for SBRT in oligometastatic breast cancer and was closed early due to futility. These are genuinely negative findings that should temper enthusiasm for SBRT in breast cancer until better patient selection strategies are developed.

Several factors may contribute to these negative results, although these explanations do not change the overall conclusion. Breast cancer patients in CURB were more likely to develop new metastatic lesions rather than progressing at pre-existing sites, suggesting that the dominant pattern of failure was systemic rather than local. Circulating tumor DNA analyses showed that SBRT led to decreases in ctDNA metrics in NSCLC but not in breast cancer, further suggesting that oligoprogressive breast cancer may represent a biologically different entity less amenable to local therapy. Additionally, 59% of control-arm patients received off-protocol SBRT after progression, which may have diluted any potential between-arm differences. The trial was also not powered for OS and was closed early after meeting its primary PFS endpoint at interim analysis. Finally, a systematic review of ten studies including 467 patients and 653 treated metastases demonstrated that SABR for oligometastatic breast cancer is safe and associated with high rates of local control. Bone-only metastases (P=0.01) were significantly associated with improved OS, while hormone receptor positivity was significantly correlated with superior local control (P=0.01) (28).

Prostate cancer

Multiple phase 2 trials have demonstrated that metastasis-directed SBRT can prolong androgen deprivation therapy (ADT)-free survival in oligometastatic prostate cancer. A meta-analysis showed pooled 1–2 years systemic therapy-free survival of 78% in prostate cancer patients treated with SBRT alone (29).

The ARTO trial demonstrated that SBRT combined with abiraterone improved PFS in oligometastatic castration-resistant prostate cancer (CRPC) (23).

The STOMP trial randomized 62 patients with ≤3 metastases detected by choline PET to surveillance versus MDT (SABR or surgery). Median ADT-free survival was 21 months with MDT versus 13 months with surveillance (HR 0.60, 80% CI: 0.40–0.90; P=0.11). Updated 5-year ADT-free survival rates were 34% for MDT versus 8% for observation (P=0.06). Importantly, the primary endpoint did not reach conventional statistical significance, and the trial was a small phase II study (n=62) not powered to detect a definitive difference. These results should therefore be interpreted as hypothesis-generating, showing a numerically favorable but statistically non-significant trend in favor of MDT (25,26).

The RADIOSA trial compared SBRT alone versus SBRT plus 6 months of ADT in 105 patients with ≤3 metastases. Median clinical PFS was 15.1 months with SBRT alone versus 32.2 months with SBRT + ADT (HR 0.43, P=0.001) (27).

The EXTEND trial is a multicenter randomized phase 2 basket trial evaluating the addition of MDT to systemic therapy in oligometastatic solid tumors. The lead-in phase enrolled 50 patients across 12 histologies, demonstrating feasible accrual, a median PFS of 13 months, a 3-year OS rate of 73%, a local control rate of 98%, and only 4% grade 3 toxicity with no grade 4–5 events (30).

The prostate-specific continuous ADT basket (n=87) subsequently demonstrated that MDT combined with continuous ADT significantly improved PFS compared with ADT alone (median 47 vs. 22 months; HR 0.50, one-sided P=0.036). In the combined analysis of both baskets (n=174), median PFS was 36 months with MDT + ADT versus 17 months with ADT alone (HR 0.45, P<0.001), with superior radiographic PFS and castration resistance-free survival. Translational correlatives showed that durable responses after MDT were associated with systemic Th1-polarizing cytokine upregulation and CD8⁺ T-cell proliferation, and that MDT induced greater T-cell receptor expansion/contraction compared with ADT alone, findings independently replicated in the ORIOLE trial (31).

The PCS-9 trial (GROUQ-PCS 9) is a multicenter, open-label, randomized phase 2 trial that specifically addressed the role of SBRT in oligometastatic CRPC, a setting previously underrepresented in the literature. The trial randomized 100 evaluable patients with ≤5 metastases to ADT-enzalutamide versus ADT-enzalutamide-SBRT to all oligometastatic sites. At a median follow-up of 4.8 years, ADT-enzalutamide-SBRT significantly improved radiographic PFS compared with ADT-enzalutamide alone [median 4.6 years (95% CI: 3.7–not reached) vs. 2.3 years (95% CI: 1.4–3.7); HR 0.48 (95% CI: 0.27–0.86); P=0.014]. Local progression was markedly more common in the control group (76% vs. 12%), confirming effective local disease control with SBRT. No grade 4 toxicities or treatment-related deaths were reported. Of note, PCS-9 relied on conventional imaging (CT, MRI, bone scan) rather than PSMA-PET, suggesting that SBRT’s efficacy persists even in conventionally staged oligometastatic CRPC (32). Finally, the WOLVERINE individual patient data meta-analysis pooled 6 randomized trials (472 patients) and found that MDT was associated with statistically significant improvements in PFS (trial-level HR 0.44, 95% CI: 0.29–0.66; P<0.0001), radiographic PFS (HR 0.60, 95% CI: 0.43–0.84; P=0.0039), and castration resistance-free survival (HR 0.58, 95% CI: 0.37–0.91; P=0.019). However, the OS analysis did not reach statistical significance (HR 0.63, 95% CI: 0.40–1.01; P=0.051) and should be interpreted as inconclusive regarding an OS benefit. While the direction of effect is consistent with a potential survival advantage, definitive conclusions about OS cannot be drawn from these data, and longer follow-up or larger studies may be needed to clarify this endpoint (33).

In summary, the available evidence reveals substantial heterogeneity in SBRT outcomes across tumor types and clinical scenarios. For oligometastatic prostate cancer, randomized phase II data consistently demonstrate improvements in PFS (HR range, 0.30–0.60 across ORIOLE, STOMP, and RADIOSA), with the WOLVERINE meta-analysis confirming a pooled PFS benefit (HR 0.44, P<0.0001), although OS benefit remains unconfirmed (HR 0.63, P=0.051). For oligoprogressive NSCLC, the CURB trial demonstrated a significant PFS benefit (HR 0.41, P=0.004), while oligoprogressive breast cancer showed no benefit in the same trial (HR 0.80, P=0.43), and the NRG-BR002 trial was closed early for futility. Renal cell carcinoma (RCC) demonstrates particularly favorable outcomes, with systemic therapy-free survival rates of 87% at 1–2 years and 5-year local control of 93%. Local control rates across tumor types and metastatic burdens generally range from 85–95% at 1–2 years, with grade 3–4 toxicity rates consistently below 10% in prospective studies. These data underscore that tumor biology and disease context, rather than lesion count alone, are the primary determinants of SBRT benefit.

RCC

RCC demonstrates particularly favorable outcomes with SBRT, with the highest systemic therapy-free survival rates (87% at 1–2 years) among all cancer types. A prospective trial of oligometastatic RCC showed excellent 5-year local control (93.3%) with no grade 3 or higher grade adverse events and median time to subsequent systemic therapy of 2.6 years (34).

Bone metastases

ASTRO endorses SBRT as a safe and effective option for initial and reirradiation treatment of symptomatic bone metastases in selected patients, with specific dose-fractionation schedules supported by high-quality randomized controlled trial (RCT) evidence demonstrating improved local control and pain outcomes compared to conventional RT (35).

For spine metastases specifically, the ESTRO has published practice guidelines addressing both the initial treatment and re-irradiation settings. The ESTRO guideline for de novo spine SBRT confirmed a pooled overall pain response rate of 83% (95% CI: 68–94%), complete pain response of 36% (95% CI: 20–53%), and 1-year local control of 94% (95% CI: 86–99%), with a vertebral fracture rate of 9% and radiation-induced myelopathy rate of 0% (95% CI: 0–2%) (36).

More recently, the joint ESTRO-International Stereotactic Radiosurgery Society (ISRS) clinical practice recommendations for re-irradiation of spinal metastases with SBRT, based on a Delphi consensus process reported pooled 1-year and 2-year local control rates of 81% and 70%, respectively, with vertebral compression fracture, nerve root damage, and myelopathy rates of 5.0%, 5.6%, and 1.7% (37).

These guidelines provide an evidence-based framework for spine SBRT that is particularly relevant in the context of polymetastatic disease, where patients may require treatment of multiple spinal sites and may have received prior RT.

The latest clinical evidence demonstrates that SBRT preserves or minimally impacts patient-reported outcomes and QoL in polymetastatic populations, with high local control rates and low toxicity. Multiple randomized trials and meta-analyses show that SBRT achieves excellent symptom relief and local control, with acute and late grade 3–5 toxicity rates consistently below 1% and pain response rates above 80% for bone metastases (38).

SBRT has increasingly been recognized as superior to conventional palliative RT for symptom control, particularly for bone metastases. Multiple randomized trials have demonstrated that SBRT provides better pain control and more durable local control compared to conventional fractionation (39,40).

A propensity-matched analysis showed that SBRT achieved superior overall pain response compared to conventional RT at 3 months (76.5% vs. 56.8%, P=0.012) and 6 months (75.9% vs. 50.0%, P=0.011) for painful non-spine bone metastases (41).

A systematic review and meta-analysis by Singh et al. [2024] evaluated 528 patients with 597 non-spinal bone metastases treated with SBRT and found excellent 1-year local control (94.6%), high pain response rates at 3 months (87.7%), and minimal toxicity (grade 3–5: 0.5%), with a 1-year OS of 71% (42).

For spine metastases, a randomized trial comparing SBRT (24 Gy in 2 fractions) versus conventional RT (20 Gy in 5 fractions) demonstrated superior outcomes with SBRT: local failure rates at 6, 12, and 24 months were 2.8%, 6.1%, and 14.8% for SBRT versus 11.2%, 28.4%, and 35.6% for conventional RT (P<0.001). The 1-year reirradiation rate was significantly lower after SBRT (2.2% vs. 15.8%, P=0.002) (40).

Brain metastases

Stereotactic radiosurgery (SRS) is a precise, image-guided RT technique (equivalent to SBRT but intracranial) that deliver ablative doses to well-defined intracranial lesions in one (SRS) or a few (SRT) fractions. By sparing surrounding healthy brain tissue, radiosurgery significantly reduce neurocognitive toxicity, such as cognitive decline, fatigue, and alopecia, compared with whole brain radiation therapy (WBRT). As a result, radiosurgery is increasingly used in patients with a limited number of brain metastases, offering effective local control with minimal invasiveness and rapid recovery.

Although SRS/SRT may be associated with higher rates of distant brain relapse, close monitoring and timely salvage therapy do not necessarily increase neurologic mortality. This is particularly relevant for elderly or frail patients, in whom WBRT is linked to greater neurocognitive decline and overall toxicity.

Focusing on patients with advanced disease, where the goal extends beyond prolonging survival to relieving symptoms caused by brain lesions, it would be reasonable to consider radiosurgery, if not for all lesions, at least for those responsible for clinical symptoms. This approach can provide relatively rapid symptomatic benefit, as opposed to delivering whole-brain irradiation, which exposes the entire brain parenchyma to radiation and is more likely to be associated with greater acute toxicity (43,44).

Technological development and implementation have markedly improved both the speed and safety of irradiating a greater number of intracranial metastases. The introduction of single-isocenter, linear accelerator-based SRS platforms—such as volumetric modulated arc therapy (VMAT) and C-arm linac systems—enables simultaneous treatment of multiple brain metastases with high precision, reducing treatment times by a factor of 4.5–8.4 compared to traditional multi-isocenter approaches. Delineation and real-time verification, allowing for smaller treatment volumes and improved sparing of healthy brain tissue reducing the risk of neurocognitive toxicity and radiation-induced complications, even as the number of treated lesions increases (45).

Pancreatic cancer

Oligometastatic pancreatic cancer represents a particularly challenging clinical scenario given the aggressive biology of this disease. Nevertheless, emerging data suggest that selected patients may benefit from ablative local therapy. A retrospective study comparing 20 patients with oligometastatic pancreatic adenocarcinoma (1–5 metastases) treated with SABR to all active metastatic sites versus 21 matched patients receiving chemotherapy alone demonstrated significantly improved polyprogression-free survival (median 40 vs. 14 months; HR 0.20, 95% CI: 0.07–0.54; P=0.0009) and OS (median 42 vs. 18 months; HR 0.21, 95% CI: 0.08–0.53; P=0.0003) in the SABR cohort. Notably, 85% of SABR-treated patients achieved ≥6 months off chemotherapy compared with 33% in the chemotherapy-only group (46).

A retrospective comparison of SBRT to all lesions (primary + oligometastases) versus SBRT to the primary tumor alone in 217 patients with synchronous oligometastatic pancreatic cancer showed improved OS (median 10.9 vs. 9.3 months; P<0.001) and PFS (median 6.5 vs. 4.1 months; P<0.001) with comprehensive SBRT (36).

The NCCN guidelines now acknowledge that in rare circumstances, patients with indolent/oligometastatic pancreatic cancer should be referred to a high-volume center for evaluation of possible MDT. These data remain retrospective and hypothesis-generating, and prospective validation is needed to define the role of SBRT in this aggressive histology.

Evolving goals of SBRT in the management of metastatic disease

An important caveat when interpreting SBRT outcomes in metastatic disease is the substantial potential for confounding, particularly from concurrent and subsequent systemic therapies. In most studies, patients received SBRT in addition to systemic therapy, making it difficult to isolate the independent contribution of local ablation to survival outcomes. Selection bias is inherent in non-randomized studies, where patients selected for SBRT tend to have better performance status, lower disease burden, and more favorable biology than the broader metastatic population. Even in randomized trials, crossover and off-protocol treatment can dilute between-arm differences, as demonstrated in the CURB trial where 59% of control-arm patients received off-protocol SBRT after progression. Furthermore, the rapidly evolving landscape of systemic therapies—including immunotherapy, targeted agents, and novel hormonal therapies—means that survival outcomes observed in older studies may not be directly applicable to current practice. These confounding factors should be considered when interpreting the evidence presented in this review and underscore the need for well-designed phase III trials with pre-specified stratification for systemic therapy to definitively establish the contribution of SBRT.

QoL

The objectives of clinical trials in patients with polymetastatic disease have evolved, shifting from a survival-based approach to a broader focus that includes parameters such as PFS, local control, and more recently, health-related quality of life (HRQOL). This shift reflects the increasing recognition that patient-centered outcomes are crucial for meaningful clinical benefit (47).

OS has historically been regarded as the gold standard endpoint due to its objectivity and direct clinical relevance. It is the most unambiguous measure of therapeutic benefit and remains the preferred endpoint in regulatory and guideline contexts, albeit in certain situations it may not represent the most appropriate approach (48).

Its use in polymetastatic disease is limited by the need for long follow-up, large sample sizes, and the confounding effects of salvage therapies and subsequent interventions. These factors can make it difficult to attribute survival benefit directly to the intervention under study, especially in settings where multiple effective therapies are available after progression (49).

There is increasing consensus that QoL and patient-reported outcome measures should be prioritized as primary or co-primary endpoints in clinical trials for advanced/metastatic disease. HRQOL and symptom control are highly valued by patients and are often more meaningful than traditional tumor-based endpoints, especially when cure is not achievable (50).

However, multiple QoL studies have demonstrated that disease progression, rather than SBRT toxicity, is the primary driver of QoL decline in oligometastatic patients.

In the SABR-5 trial, disease progression [odds ratio (OR) 5.23, P=0.007] was the strongest predictor of persistent QoL decline, while SBRT-associated toxicity showed only a trend toward increased risk. Similarly, in a study of oligometastatic patients receiving SBRT, only progressors demonstrated statistically and clinically significant declines in global health/QoL scores (−8.8 points, P=0.01), while non progressors maintained stable QoL. This finding has important implications: the goal of SBRT should be to delay or prevent progression, as progression itself causes greater QoL deterioration most of cases than treatment toxicity (51).

Hence, studies showing that SBRT preserves QoL compared to SOC likely reflect the PFS benefit rather than inherently superior tolerability (52,53).

Validated, disease-specific PRO instruments and responder criteria are recommended to ensure robust assessment of patient benefit. Guidelines and consensus statements now advocate for the systematic inclusion of PROs in trial design, with emphasis on capturing clinically meaningful changes in symptoms and functioning (49).

Symptoms control and delay of systemic treatment

SBRT delivers highly conformal, ablative doses to metastatic lesions, resulting in high local control rates often exceeding 70–90%, with severe toxicity rates typically below 5% (54).

This favorable toxicity profile is especially important in patients with limited life expectancy, where maintaining function and minimizing treatment-related morbidity are paramount (55).

For polymetastatic patients, local control of symptomatic lesions can prevent or alleviate pain, neurologic compromise, or organ dysfunction, directly improving QoL and functional status (9).

Palliative RT to the primary tumor effectively relieves local symptoms caused by the tumor itself and it is sometimes crucial for symptom control, including relief of pain, bleeding, and compression syndromes, which significantly improves QoL, even in patients with limited life expectancy. Beyond symptom control, palliative RT to the primary tumor can prevent severe complications from cancer progression such as spinal cord compression, pathologic fractures, or complete obstruction, which would otherwise require more invasive interventions. SBRT to the celiac plexus is an emerging, non-invasive palliative technique for controlling refractory upper abdominal and lower back pain (retroperitoneal pain syndrome) in patients with pancreatic cancer and other tumors invading the celiac axis, particularly important for polymetastatic patients with limited life expectancy (56).

SBRT’s short treatment duration and noninvasive nature further reduce the burden of therapy, allowing patients to continue systemic treatments or avoid escalation to more toxic regimens. Prolonging PFS and delaying symptomatic progression are meaningful endpoints, as they translate to sustained QoL and reduced need for additional interventions (22).

In prospective studies, SBRT has been shown to delay the need for systemic therapy, thereby reducing exposure to systemic toxicities and preserving functional status. Systematic reviews and meta-analyses confirm that SBRT does not cause significant quality-of-life deterioration, and in some settings, allows patients to defer systemic therapy, which is associated with improved patient-reported outcomes (29).

Overall, SBRT is a well-tolerated local therapy that maintains or improves QoL in polymetastatic patients, especially when symptom control and local disease management are primary goals.

Cost-benefit balance

Highly conformal RT techniques such as intensity-modulated radiotherapy (IMRT) and VMAT could be considered cost-effective in palliative patients, particularly when the goal is to minimize dose to adjacent healthy organs, reduce toxicity, and preserve QoL during a limited life expectancy, even though these techniques do not improve OS in this setting. In a randomized trial, palliative VMAT induced significantly less global quality-of-life deterioration at 4 weeks compared to 3D-CRT, with better preservation of physical, role, and social functioning (57).

The primary advantage of IMRT/VMAT in palliative care lies in superior organ-at-risk (OAR) sparing. Dosimetric studies consistently demonstrate that VMAT achieves significantly lower doses to critical structures such as the spinal cord, lungs, esophagus, and heart compared to conventional 3D-CRT.

Similarly, esophageal-sparing IMRT in palliative thoracic RT has been shown to reduce symptomatic esophagitis from approximately 25% to as low as 2%, which is clinically meaningful for patients with limited life expectancy (58).

Historically, the cost-effectiveness of IMRT/VMAT was limited by the high resource consumption required for manual contouring and treatment planning. However, modern automated planning systems, knowledge-based algorithms, and artificial intelligence (AI)-driven auto-segmentation tools have substantially reduced planning time, by up to 50–70% in some reports, enabling rapid generation of high-quality plans with lower personnel costs. This technological evolution has shifted the cost-benefit balance in favor of advanced techniques, even in palliative scenarios (59).

However, the lack of survival benefit, the need for specialized infrastructure, and the limited high-quality comparative evidence remain important caveats. Patient selection, prioritizing those with longer expected survival, proximity to critical structures, or higher risk of toxicity is essential to maximize the value of these advanced techniques in the palliative setting.

Robust evidence supports the use of single-fraction 3D conformal palliative RT (e.g., 8 Gy in 1 fraction) as a highly effective, simple, and convenient treatment for symptomatic bone metastases, with multiple RCTs and meta-analyses demonstrating equivalent pain relief compared to longer fractionation schedules (60,61).

The RTOG 97-14 trial and the SCORAD trial, among others, confirmed that single-fraction RT provides similar pain control to multifraction regimens, with lower acute toxicity and reduced treatment burden for patients with limited life expectancy. These regimens are straightforward to plan, require minimal resources, and are particularly suited for patients with poor performance status or short prognosis.

The expansion of SBRT indications to polymetastatic and oligometastatic scenarios does not diminish the fundamental role of conventional palliative RT in appropriately selected patients and for patients with limited prognosis, poor performance status, or logistical constraints, conventional single-fraction or short-course 3D conformal RT remains the SOC and is supported by high-quality evidence. Guidelines from ASTRO, NCCN, and other societies consistently recommend that dose and fractionation should be individualized based on goals of care, symptoms, performance status, and logistical considerations (35).

Conclusions

The evidence reviewed in this manuscript supports several conclusions, each calibrated to the corresponding level of evidence. First, SBRT is safe and effective for patients with 1–5 oligometastases, supported by randomized phase II evidence (SABR-COMET) and large prospective cohorts (SABR-5), with phase III confirmation pending (SABR-COMET-3). Second, extending SBRT to 5–10 metastases is biologically plausible and under active investigation in phase III trials (SABR-COMET-10, SABR-SYNC), but definitive evidence is not yet available. Third, comprehensive SBRT for >10 metastases has demonstrated preliminary safety in a single phase I study (ARREST) and should be considered exploratory and hypothesis-generating only. Fourth, tumor biology, organ distribution, and disease context appear to be stronger determinants of SBRT benefit than lesion count alone, as demonstrated by the contrasting outcomes in NSCLC versus breast cancer in the CURB trial and the consistently favorable results in prostate cancer and RCC across multiple randomized studies. Fifth, QoL and symptom control are increasingly recognized as meaningful endpoints, with evidence suggesting that disease progression rather than SBRT toxicity is the primary driver of quality-of-life decline. These findings collectively support a shift from a rigid lesion-count-based paradigm toward individualized, biology-informed decision-making, although phase III evidence is needed before practice-changing recommendations can be made for most clinical scenarios.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://apm.amegroups.com/article/view/10.21037/apm-2026-0030/rc

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Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-2026-0030/coif). The authors have no conflicts of interest to declare.

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