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Neoadjuvant chemotherapy for non‐metastatic pancreatic cancer

Dear Editor, We congratulate Dr Inoue and colleagues on their important and relevant publication in which outcomes for borderline resectable pancreatic cancer (BRPC) in patients who received gemcitabine and nabpaclitaxel (GNPNAT) neoadjuvant therapy (NAT) were compared to upfront surgery (UFS).1 The study included 151 consecutive patients of whom 55 received preoperative GNPNAT and 96 underwent UFS. Following GNPNAT, 46 patients (84%) underwent surgery of whom three (5%) had nontherapeutic procedures, compared to 23 (24%) in the UFS group (P = .004). A significant benefit was demonstrated in GNPNAT patients with higher R0resection rates and longer 3year median overall survival (OS) (31.9 vs 18.1 months, P = .014). The authors concluded that GNPNAT also contributed to improved tumor suppression and patient selection. In a recently published systematic review and network metaanalysis, we assessed equivalence of OS in patients with BRPC and locally advanced unresectable PC (LAPC) treated with or without NAT, with or without surgical resection.2 Using a frequentist network metaanalysis, the review included 39 studies published between 1 January 2009 and 21 August 2019, comprising 14 065 patients in a network of eight unique treatment subgroups. Hypothesizing equivalent OS for BRPC and locally advanced tumors that were initially assessed as unresectable (LAUR), hazard ratios for OS (primary outcome) and OS in BRPC, LAUR, and upfront resectable (UFR) PC (secondary outcomes) were analyzed. Overall survival was better for BRPC than LAUR patients following surgery both with and without NAT. In keeping with the results of the Inoue study, we found that NAT prior to surgery was associated with longer OS for BRPC. In addition, we showed that NAT prior to surgery was also associated with better OS in UFR and LAUR patients. The results of our network metaanalysis contradict the hypothesis that patients with LAUR PC have equivalent survival to those with BRPC disease. Those with LAUR PC appear to have a shorter OS. The results suggest a benefit of NAT across the spectrum of nonmetastatic PC regardless of initial disease extent. With mounting evidence that NAT may also be beneficial for UFR PC, an interesting further study for Inoue and colleagues to consider would be an analysis of GNPNAT in UFR patients to challenge the existing status quo. If the findings in their study on BRPC of higher rates of R0 resection, fewer nontherapeutic procedures, and better OS could be duplicated in UFR patients, findings would support the use of NAT regardless of anatomical classification. This would underscore the importance of disease progression as a surrogate for unfavorable tumor biology and is likely to improve the selection of patients who would benefit from surgery.