Meta‐analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. BJS 2018; 105: 946-958.

Published: 30th April 2018

Authors: E. Versteijne, J. A. Vogel, M. G. Besselink, O. R. C. Busch, J. W. Wilmink, J. G. Daams et al.

Background

Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer.

Method

MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment.

Results

In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients.

Conclusion

Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer.

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1 Comment

Elena Rangelova

1 month ago

The meta-analysis by Versteijne et al., neoadjuvant oncologic treatment (NAT) for resectable/borderline-resectable pancreatic cancer (R-BRPC), gave a significant survival advantage to upfront surgery (S) both in the intention-to-treat analysis and for the patients undergoing resection.

As exciting the finding appears, the conclusion should be interpreted with care. First, NAT comprises of mixture of regimens, including FOLFIRINOX, which overrules significantly gemcitabine in terms of survival for locally advanced PC (1). The advantage of FOLFIRINOX could be erroneously translated as a benefit of the whole group of chemotherapy.

Second, In the NAT group, adjuvant chemotherapy (ACT) was not even reported in 17/35 studies, and it is still the gold standard (2). The argument that patients may not receive ACT due to deconditioning after surgery is invalid, since patients who are too old or sick for ACT would be so even for NAT. Thus, there is already a selection bias in the NAT group. Also, FOLFIRINOX is not part of ACT, although a recent trial showed clear superiority to standard ACT even postoperatively (3).

Furthermore, there is a paradoxically higher resection rate for BR- over R-PC suggesting a discrepancy in the technical possibility for radical surgical resection among the studies. Resection itself has undoubtedly the highest impact on survival for PC.

Is it really the timing or the type of chemotherapy that makes a difference for survival after radical surgery? There are no trials comparing neoadjuvant to adjuvant FOLFIRINOX for R-BRPC. Until we have this data all meta-analysis performed will be biased.

Rangelova E
Valente R
Del Chiaro M

Pancreatic Unit at Dept of Upper GI Cancer
Karolinska University Hospital, K42
14186 Stockholm
Sweden
Elena.Rangelova@ki.se

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