How would you manage initially unresectable node-negative pancreatic adenocarcinoma that after upfront chemotherapy achieves a complete radiographic response on interval MRI and CT?

This is an interesting question and, in my experience, something that is not commonly encountered clinically. I will assume here that the patient has no visible sites of disease elsewhere.

Still, given that scans are a poor predictor for pathologic response and complete response in pancreatic cancer...

Could be BRCA+ or misdiagnosis. Consider molecular testing and path review if indicated.

I would give ablative RT 50Gy in 5# with MRL or 67.5Gy in 15# with Conventional IGRT, IMRT, DIBH and selective adaptive planning. Our soon to be published results show a similar OS to resection by MSK surgeons...