Neoadjuvant treatment in pancreatic cancer: Evidence-based medicine? A systematic review and meta-analysis

Abstract

Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable disease, selecting patients for surgery and administering therapy to each patient. The aim of this systematic review is to analyze the state of the art on neoadjuvant protocols for non-metastatic PaC. A literature search over the last 10 years was conducted, and papers had to be focused on resectable, borderline resectable (BLR) or locally advanced (LA) histo- or cytologically proven PaC; to be prospective studies or prospectively collected databases; to report percentage of protocol achievement and survival data at least in an intention-to-treat (ITT) analysis. Twelve studies were eligible for systematic review. Studies included a total of 624 patients: 248 resectable, 268 BLR, 71 LA and 37 non-specified. All studies were included for meta-analysis. ITT overall survival (OS) was 16.7 months (95% CI 15.16-18.26 months); for resected patients OS was 22.78 months (95% CI 20.42-25.16), and for eventually non-resected patients it was 9.89 months (95% CI 8.84-10.96). Neoadjuvant approaches for resectable, BLR and LA PaC are spreading. Outcomes tend to be better outside an RCT context, but strong evidences are lacking. Actually such treatments should be performed only in a randomized clinical trial setting.

Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

“…Surgical resection remains a patient's best chance at curative therapy when tumors are detected early (3). However, even in successfully resected patients, prognosis remains grim, with median overall survival estimated as less than 23 months (4). As a result, surgical resection is often combined with chemotherapy and/or radiation therapy (3).…”

Patterns of recurrence after curative-intent surgery for pancreas cancer reinforce the importance of locoregional control and adjuvant chemotherapy

“…More importantly, a better patientcentred systemic approach to control of the disease should be the focus for improving survival in patients with pancreatic cancer. Indeed, suggestions of a more aggressive neoadjuvant approach with chemotherapy to most, if not all, patients with resectable disease has been proposed [10][11][12] . While uncontrolled case-series of neoadjuvant chemotherapy has demonstrated an effect on recurrence patterns in resectable disease 11 , with reduction in both time to as well as number of locoregional and distant metastasis, results from randomised trials are pending for this strategy 13 .…”

Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

“…Several meta‐analyses investigated the efficacy of neoadjuvant . D'Angelo et al summarized the survival outcome of 12 neoadjuvant studies including 628 patients. The estimated median OS rate of the ITT cohort and the resected cohort were 16.7 months and 22.78 months, respectively.…”

“…[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Several meta-analyses investigated the efficacy of neoadjuvant. 29 including only ITT data. 32 The results of the meta-analysis showed that the patients treated with neoadjuvant had better long-term survival than those treated with upfront surgery.…”