Given the updated results of the PREOPANC study, how can gemcitabine-based neoadjuvant chemoradiation be best incorporated into the treatment of resectable or borderline resectable pancreatic cancer?

The PREOPANC-1 trial and the study by Jang et al., PMID 29462005 are currently the only 2 published randomized trials comparing pre-op CRT vs up-front surgery for resectable/borderline resectable PDAC- each of which has now demonstrated an overall survival benefit. The obvious critique is the standard of care arm from each study (up-front surgery) as neoadjuvant therapy (chemo +- RT) is rapidly becoming the new standard for all subsets of localized disease and certainly is for borderline resectable disease. The benefits of neoadjuvant tx are multi-fold: 1) early systemic therapy to control occult distant disease, 2) cytoreduction to help facilitate an R0 resection, and perhaps most notably 3) provide a test of time/treatment response to bet...

The results of PREOPANC, although powerful, is unlikely to change the current common practice of at least a segment of neoadjuvant therapy for PDAC (with CRT component when appropriate based on multidisciplinary discussion).

In addition to the nature of the chemotherapy in both arms, there were 2 main limitations:

1. Including both resectable and BR cases where the impact of locoregional intervention such as radiation can be variable.
2. Testing 2 changes at the same time: one being radiation and the other being chemotherapy delivery. In the Neoadjuvant arm, the majority of the patients received the neoadjuvant segment which has 3 cycles of gemcitabine while almost half the patients on the upfront surgery arm received no chemo, and only ~ 45% rec...