It remains unclear whether adjuvant chemo-radiotherapy (4) or chemotherapy alone (8) provides the best adjuvant result, each approach appearing to confer a survival benefit over surgery alone, in these respective reports. It is also possible that neoadjuvant radio-chemotherapy provides the best curative result by allowing surgical downstaging and improving the resectability rate of pancreatic cancer ( 5, 6, 7). To complicate matters though, neoadjuvant versus adjuvant therapy has never been tested, so the answer may never be known, and specific treatment protocols seem to develop according to institutional preference. In any event, the magnitude of survival improvement is relatively small with any surgical adjuvant approach and the majority of patients so treated still succumb to their disease.

To make matters worse, a majority of pancreatic cancer patients are not even eligible for attempted surgical cure, due to local tumor invasion of adjacent vital structures such as the superior mesenteric artery, or due to the existence of metastatic disease (1, 2, 3).

Nonsurgical approaches have also been used in unresectable pancreatic lesions, including radiotherapy, chemotherapy and combined radiotherapy-chemotherapy (9, 10, 11, 12, 13, 14).  While palliation and modest life extension may be achieved with these approaches, there is essentially zero curative potential. Combined chemo-radiotherapy has been proven superior to radiation therapy alone in a randomized trial (11, 12) though it is not clearly established that chemotherapy-radiotherapy is superior to chemotherapy alone (13).

With radiotherapy, it is very challenging to deliver a potentially curative radiation dose to the pancreatic tumor volume, due to its typical close approximation to the stomach, duodenum, small intestine, large intestine, liver, kidneys and spinal cord. With dose escalated modern techniques such as intensity modulated radiotherapy (IMRT), upper abdominal tolerance to radiation appears improved, due to improved conformality of the high dose volume (14,15). There is still no published evidence of added survival benefit with IMRT, though the 69% 1 year survival rate in inoperable patients reported with the combination of IMRT and capecitabine seems potentially superior to historical results, and the toxicity in this study was within acceptable limits (15).