SABR in pancreatic cancer: Current evidence supporting clinical practice
Executive summary
Across multiple prospective trials, institutional cohorts, and real-world datasets, Stereotactic ablative radiotherapy (SABR) has emerged as a technically feasible and clinically meaningful local treatment option in selected patients with pancreatic cancer. The strength of evidence varies by disease state, with the most consistent data supporting use in locally advanced and oligometastatic settings and emerging but less definitive evidence in borderline resectable disease.
In locally advanced pancreatic cancer, MRI-guided SABR achieves high local control (approximately 90% at 1 year and 80% at 2 years) with low rates of severe gastrointestinal toxicity. Cohort-level survival outcomes compare favourably with historical chemotherapy-alone series, particularly in well-selected patients.
In oligometastatic disease, phase II and randomised data demonstrate improved progression-free survival when SABR is added to systemic therapy, without increased high-grade toxicity. Quality of life is generally maintained, supporting SABR as a metastasis-directed option for carefully selected patients.
In advanced metastatic disease in the palliative setting, phase II evidence supports SABR-directed coeliac plexus radiosurgery for refractory pain. More than half of evaluable patients achieved meaningful pain reduction following a single 25 Gy fraction, indicating a potential non-invasive symptom-control strategy.
Across these disease states, SABR offers practical advantages, including short treatment courses that minimise interruption to systemic therapy, favourable toxicity profiles, and generally preserved quality of life. These attributes make SABR an attractive component of multidisciplinary treatment pathways when aligned with appropriate patient selection and modern systemic therapy.
Introduction
Despite improvements in treatment over recent decades, the overall 5-year survival for PDAC remains under 5%. For patients who undergo successful surgical resection, 5-year survival increases to around 20%. However, only about 10% of patients present with early-stage disease, meaning that upfront surgery is not feasible for most individuals with PDAC. Even when feasible, surgery carries substantial perioperative morbidity, delays systemic therapy, and does not eliminate the high risk of local and distant recurrence.
Radiotherapy traditionally had a limited role due to dose constraints imposed by adjacent gastrointestinal organs. The emergence of SABR has transformed local therapy options. SABR’s short course facilitates integration with systemic therapy and provides a meaningful break from chemotherapy, with favourable quality-of-life outcomes across multiple studies.
Current evidence suggests SABR may be appropriate for the majority of pancreatic cancer patients at some point in their treatment pathway – whether as definitive therapy, neoadjuvant treatment, conversion therapy, consolidative therapy, palliation, or for oligometastatic disease.
Locally Advanced Pancreatic Cancer (LAPC)
1. Prospective single-centre trial using MRI-guided SABR
Study design and patient population
This prospective single-centre cohort evaluated MRI-guided SABR delivered after induction chemotherapy (predominantly FOLFIRINOX) in 74 patients with unresectable LAPC (median age 66; 46% with Karnofsky Performance Status ≥90). All patients received 40 Gy in five fractions over two weeks.
Clinical interpretation
MRI-guided SABR provides effective consolidative local therapy after chemotherapy with excellent local control and low toxicity. Baseline performance status, age, and symptom burden may help identify patients most likely to benefit.
2. Phase II multicentre trial using MRI-guided adaptive SABR
Study design and patient population
This multicentre, prospective, single-arm phase II trial provided the first prospective evaluation of MRI-guided SABR in borderline resectable pancreatic cancer (BRPC) and remains the largest SABR study conducted in pancreatic cancer. The study enrolled 136 patients, including 56.6% with LAPC, after at least three months of induction chemotherapy (most commonly FOLFIRINOX) and with a CA19-9 level of 500 U/mL or below. All patients received 50 Gy in five fractions using a 0.35 T MRI-guided system, with optional elective nodal coverage. Surgery and systemic therapy were permitted after treatment.
Clinical interpretation
MRI-guided adaptive SABR can be delivered safely in LAPC following induction chemotherapy, achieving high rates of durable local control with a low incidence of severe treatment-related gastrointestinal toxicity. Although survival outcomes are reported at the cohort level, the consistency of local control and safety data, alongside the feasibility of delivering ablative doses in anatomically complex disease, supports SMART as a robust consolidative local treatment strategy in LAPC.
3. Real-world single-centre cohort using MRI-guided adaptive SABR
Study design and patient population
This retrospective single-centre cohort included 117 patients treated with SMART across resectable, borderline resectable, unresectable, and recurrent pancreatic cancer presentations. All 532 fractions underwent full daily on-table adaptation. Most patients had advanced disease, and the median delivered dose was 40 Gy in five fractions.
Clinical interpretation
SMART is feasible and safe across a broad range of pancreatic cancer presentations in routine practice. While survival outcomes were lower than in other prospective trials, this likely reflects lower median dose, greater disease heterogeneity, and longer time to treatment. These data support continued refinement of dose selection and patient selection in real-world settings.
Key takeaway for SABR in locally advanced pancreatic cancer
The application of SABR in locally advanced pancreatic cancer is supported by a mature and increasingly consistent body of clinical evidence. Prospective trials and real-world cohorts demonstrate high and durable local control rates, with acceptable overall survival outcomes when SABR is delivered following induction chemotherapy. Importantly, modern MRI-guided and adaptive techniques have enabled safe dose escalation with low rates of severe gastrointestinal toxicity. While distant progression remains common and survival benefits are influenced by systemic disease biology, SABR is well established as an effective consolidative local treatment strategy in appropriately selected patients.
Oligometastatic Pancreatic Cancer
1. Phase II multicentre trial using SABR for up to 5 oligometastatic sites
Study design and patient population
The SABR-5 trial was a prospective, single-arm, population-based phase II study conducted across six cancer centres in British Columbia between 2016 and 2020. It evaluated longitudinal quality of life following SABR to up to five oligometastatic lesions. Patients completed site-specific QoL instruments at baseline and at multiple time points up to 36 months. A total of 133 patients with baseline and at least one follow-up assessment were included.
Clinical interpretation
QoL was generally stable over the three years following SABR, with most declines being temporary and not sustained. These findings support SABR as a well-tolerated treatment option for patients with oligometastatic disease, although further work is required to identify predictors of late QoL deterioration and to optimise supportive care.
2. Phase II multicentre trial using SABR for up to 5 oligometastatic sites
Study design and patient population
The EXTEND trial was a multicentre, randomised, phase II basket study evaluating whether adding metastasis-directed therapy (MDT), most commonly SABR, to systemic therapy could improve progression-free survival in oligometastatic pancreatic cancer. Patients with five or fewer metastatic lesions were randomised 1:1 to systemic therapy alone or systemic therapy plus MDT. A total of 41 patients were enrolled, and 40 (19 MDT, 21 control) were eligible for the primary analysis.
Clinical interpretation
The EXTEND trial shows that adding SABR to systemic therapy significantly prolongs progression-free survival in carefully selected patients with oligometastatic pancreatic cancer, with no increase in high-grade toxicity. These results support the integration of SABR into multimodal treatment pathways, pending confirmation in larger prospective studies.
Key takeaway for SABR in oligometastatic disease
The use of SABR in oligometastatic pancreatic cancer is supported by emerging but increasingly compelling prospective evidence. Randomised phase II data demonstrate a clinically meaningful improvement in progression-free survival when SABR is added to systemic therapy, without an increase in high-grade toxicity. Population-based studies further support the tolerability of SABR, with most patients maintaining stable quality of life over time. Although overall survival data remain immature and patient selection is critical, current evidence supports SABR as a rational metastasis-directed approach within multidisciplinary treatment pathways for carefully selected patients.
Advanced Metastatic Pancreatic Cancer
1. Phase II multicentre trial using SABR for advanced metastatic pancreatic cancer in the palliative setting
Study design and patient population
This multicentre, single-arm, phase II study evaluated the efficacy and safety of single-fraction coeliac plexus radiosurgery for refractory retroperitoneal pain syndrome in patients with pancreatic or other upper gastrointestinal malignancies. The study was conducted across eight centres in five countries.
Eligible patients had an average pain score of 5-10 on the Brief Pain Inventory short form (BPI-SF), an ECOG performance status of 0-2, and radiographic involvement of the coeliac axis. Patients received a single 25 Gy fraction of external-beam radiotherapy directed to the coeliac plexus.
A total of 125 patients were treated, of whom 90 were evaluable for the primary endpoint. The majority of patients (92%) had pancreatic cancer, and 86% had metastatic disease. Median baseline pain score was 6.
Clinical interpretation
Single-fraction coeliac plexus radiosurgery demonstrated clinically meaningful pain reduction in over half of evaluable patients with refractory retroperitoneal pain syndrome. Toxicity was consistent with the advanced disease context and prior treatments, with relatively few events deemed directly attributable to radiotherapy.
These findings suggest that targeted ablative radiation to the coeliac plexus may represent a non-invasive palliative option for patients with severe cancer-related abdominal or back pain. However, the absence of a comparator arm limits definitive conclusions regarding relative efficacy versus established approaches such as coeliac plexus block or neurolysis. Randomised evaluation is warranted.
Key takeaway for SABR in advanced metastatic disease in the palliative setting
Prospective phase II evidence supports coeliac plexus radiosurgery as a feasible, non-invasive strategy for pain control in patients with advanced pancreatic cancer and refractory retroperitoneal pain syndrome. In a predominantly metastatic population, more than half of evaluable patients achieved meaningful pain reduction following a single 25 Gy fraction. While treatment-related serious adverse events were uncommon, careful patient selection remains essential. Further comparative trials are needed to define the role of this approach relative to conventional interventional pain procedures within multidisciplinary palliative care pathways.
Conclusion
Maintaining rigorous, evidence-based patient selection and thoughtful integration with systemic therapy remains central to the safe and effective use of SABR in pancreatic cancer. In settings such as locally advanced and oligometastatic disease, SABR is now supported by a growing body of prospective and real-world evidence and represents an important component of modern multidisciplinary care.
At GenesisCare, SABR is applied within multidisciplinary pathways, guided by the best available clinical data and ongoing appraisal of emerging evidence. This approach ensures that SABR is offered to patients most likely to benefit, while upholding the highest standards of treatment quality, safety, and personalised cancer care.
Learn more about GenesisCare’s Rapid Access Pathway for pancreatic cancer, with SABR treatment available within 5 working days of referral.
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