Expanding roles for SABR in pancreatic cancer: Emerging evidence and future directions
Executive summary
Stereotactic ablative radiotherapy (SABR) is being increasingly explored beyond established indications in pancreatic cancer, particularly in borderline resectable and technically resectable disease. While early data are promising, these applications remain investigational and require careful patient selection.
In borderline resectable pancreatic cancer, prospective studies using MRI-guided SABR demonstrate meaningful rates of surgical conversion and high rates of margin-negative resection in selected patients. However, randomised data incorporating heterogeneous radiotherapy techniques have not shown a clear survival benefit, and further SABR-specific neoadjuvant trials are needed.
In technically resectable disease, early cohort data suggest that ablative radiotherapy may offer a non-operative alternative for medically inoperable patients, achieving encouraging local control and survival outcomes despite limited chemotherapy use. However, these findings are based on small, non-randomised cohorts and require prospective validation.
Overall, SABR in these settings should be considered investigational and delivered within multidisciplinary frameworks, with ongoing evaluation of emerging evidence to define its optimal role.
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.
Stereotactic ablative radiotherapy (SABR) is now an established component of treatment for selected patients with pancreatic cancer, particularly in locally advanced and oligometastatic settings where it provides durable local control with acceptable toxicity.
The current evidence supporting SABR in these established indications is reviewed in a companion here
More recently, SABR is being explored earlier in the disease pathway, including in patients with borderline resectable and technically resectable pancreatic cancer. These approaches aim to improve surgical outcomes, expand treatment options for patients who are not surgical candidates, and potentially redefine local therapy paradigms.
However, the evidence base in these settings remains evolving. Most data are derived from single-arm prospective studies or retrospective cohorts, and randomised evidence is limited.
Borderline Resectable Pancreatic Cancer (BRPC)
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 adaptive SABR in BRPC and remains the largest SABR study conducted in pancreatic cancer. The study enrolled 136 patients, including 43.4% with BRPC, 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 SABR was delivered safely in BRPC and was associated with meaningful rates of surgical conversion and high R0 resection rates in selected patients. The strong association between resection and improved survival highlights the potential role of SMART in facilitating surgical eligibility, while maintaining an acceptable toxicity profile. These findings support continued investigation of SABR as part of neoadjuvant strategies in BRPC, with careful patient selection.
Phase II multicentre, randomised trial using SABR
Study design and patient population
This multicentre phase II randomised trial evaluated whether adding preoperative SABR or hypofractionated image-guided radiotherapy to neoadjuvant mFOLFIRINOX improves outcomes in BRPC. A total of 126 patients were randomised either to eight cycles of mFOLFIRINOX alone or to seven cycles followed by SABR (33-40 Gy in five fractions) or HIGRT (25 Gy in five fractions) before planned resection and adjuvant FOLFOX6.
Clinical interpretation
Although the intent-to-treat analysis did not show benefit from adding radiotherapy, interpretation is limited by the inclusion of two radiotherapy modalities, early arm closure, and strict R0-based stopping rules. The high R0 resection rate among SABR-treated patients who reached surgery highlights the need for SABR-specific neoadjuvant trials to determine its true contribution in BRPC.
Key takeaway for SABR in borderline resectable pancreatic cancer
The role of SABR in borderline resectable pancreatic cancer remains investigational. Single-arm prospective studies using MRI-guided SABR demonstrate meaningful rates of surgical conversion and high margin-negative resection rates in selected patients, alongside a favourable toxicity profile. However, randomised data incorporating heterogeneous radiotherapy techniques have not shown a clear survival benefit. As such, SABR in this setting should be applied selectively, with careful patient selection and ongoing appraisal of emerging SABR-specific neoadjuvant trial data to better define its optimal role in patient care.
Technically Resectable Pancreatic Cancer
Phase II multicentre trial using MRI-guided adaptive SABR
Study design and patient population
This single-centre cohort study evaluated the outcomes of definitive ablative radiation therapy in 25 patients with radiographically resectable T1-2N0-1M0 PDAC. Patients were deemed unsuitable for surgical resection due to non-cancer-related comorbidities. The cohort was elderly (median age 80 years), with poor baseline functional status (80% with Karnofsky Performance Status ≤80). Seventeen patients (68%) received induction chemotherapy for a median duration of 2.9 months prior to radiation.
All patients received definitive ablative radiation exceeding a biologically effective dose of 97.5 Gy, delivered using daily CT or MRI guidance with daily or selective adaptive planning. Specifically, 2 of the 25 patients received 50 Gy in 5 fractions on an MRI-guided linear accelerator.
Clinical interpretation
In this highly selected cohort of elderly, medically inoperable patients with technically resectable pancreatic cancer, definitive ablative radiation therapy achieved encouraging local control and overall survival outcomes despite limited use of chemotherapy and poor baseline performance status. These findings suggest that non-operative management with ablative-dose radiation may represent a viable alternative to surgery for selected patients in whom operative morbidity or functional consequences are prohibitive.
Key takeaway for SABR in technically resectable pancreatic cancer
The role of SABR in technically resectable pancreatic cancer remains investigational. The reported outcomes largely reflect CT-guided ablative radiotherapy, not MRI-guided SABR. MRI-guided radiotherapy is demonstrated to be feasible but was not evaluated for efficacy or toxicity comparisons in this study.
Conclusion
The role of SABR in borderline resectable and technically resectable pancreatic cancer continues to evolve. While early data suggest potential benefits in selected patients, including surgical facilitation and non-operative management in high-risk populations, these approaches remain investigational.
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. 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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