Neoadjuvant radiotherapy in pancreatic cancer: better margins, same survival

Design

Retrospective propensity-matched cohort, two centres

Population

452 matched patients resected after neoadjuvant therapy for pancreatic cancer

Primary outcome

Event-free survival, recurrence pattern and overall survival

Effect

Overall survival HR 1.02 (0.79 to 1.32); R0 85.0% vs 52.2%

This retrospective cohort from two high-volume centres matched 226 patients who had neoadjuvant chemotherapy plus radiotherapy with 226 who had chemotherapy alone before resection of pancreatic ductal adenocarcinoma. Chemotherapy was FOLFIRINOX or gemcitabine with nab-paclitaxel; most tumours were resectable or borderline resectable, and median follow-up was 44 months.

Radiotherapy was associated with more R0 resections (85.0% vs 52.2%), more node-negative specimens (61.5% vs 33.6%) and slightly more complete pathological responses (6.6% vs 4.4%). But it was not associated with less locoregional recurrence (subdistribution HR 0.90, 95% CI 0.53 to 1.54), event-free survival (HR 1.10, 0.88 to 1.37) or overall survival (HR 1.02, 0.79 to 1.32). About half of each group first recurred at a distant site.

The finding fits the view that pancreatic cancer is mostly a systemic disease by the time it is resected. For multidisciplinary teams, it argues against adding radiotherapy routinely for margin clearance alone, but it is observational, and randomised data remain the standard for changing protocols.

• Do not treat a clearer margin after radiotherapy as a proxy for longer survival
• Prioritise completing effective systemic chemotherapy before resection
• Discuss the added toxicity and delay of radiotherapy against an unproven survival benefit
• Follow your multidisciplinary protocol until randomised evidence settles the question

Why it matters

It separates a surgical surrogate — the clear margin — from the outcome patients care about.

Don't overread it

This is a matched retrospective cohort; unmeasured differences in who was given radiotherapy may remain.

The statistics, in plain English

Hazard ratios near 1.0 with intervals crossing 1.0 mean no detectable survival difference. The R0 gap is large, but a surrogate like margin status only matters if it changes survival, and here it did not.

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