Original articleAdjuvant chemotherapy, with or without postoperative radiotherapy, for resectable advanced pancreatic adenocarcinoma: Continue or stop?
Introduction
Globally, pancreatic adenocarcinoma (PAC) is one of the most aggressive tumor types. It is the fourth most common cause of cancer-related deaths, and has a five-year survival rate of less than 5% [1]. Surgical resection is the only potentially curative treatment for managing PAC [2]. Surgical resection offers a significantly improved prognosis, with a median survival after resection of 14–20 months and up to 25% 5-year survival rate [3]. This is underlined by studies showing a distinct advantage of potentially curative (R0) versus palliative (R1/R2) surgery [4], [5].
A number of studies have investigated the use of adjuvant therapy for patients with resectable PAC. Most of these studies have reported positive results. In 1985, the efficacy of combined radiation and fluorouracil as an adjuvant therapy for pancreatic cancer was initially suggested by the Gastrointestinal Tumor Study Group (GITSG) [6]. In this trial, the overall survival (OS) for PAC patients undergoing pancreaticoduodenectomy could be prolonged almost two-fold with postoperative chemoradiation treatment. In 2007, the Charite’ Onkologie Clinical Studies in GI Cancer (CONKO)-001 trial reported improved disease-free survival (DFS) in patients receiving adjuvant gemcitabine compared to those receiving surgery alone [7]. Nevertheless, with regard to adjuvant therapy for PAC, there are still some controversial issues, including whether the use of adjuvant radiotherapy is necessary and which chemotherapy regimen is the best choice. The apparent lack of consensus is due to the inconsistency of available data.
The aim of the article is to perform a focused review of adjuvant therapies for the treatment of resectable PAC. We critically discussed the clinical benefits of adjuvant chemotherapy with or without radiotherapy as well as the optimal regimen of adjuvant therapy based on the results of randomized clinical trials. This review will provide more powerful statistical evidence for clinicians to use when choosing the optimal therapy for PAC patients following an operation.
Section snippets
Study selection
We performed a literature search from 1965 to 2010 for all clinical trials that evaluated the efficacy of adjuvant chemotherapy for the treatment of pancreatic adenocarcinoma. The search was performed with Medline database and EMBASE using the terms “adjuvant,” “trial” and “pancreatic cancer” (no restrictions on language). In addition to full publications, abstracts presented at the annual meetings of the American Society of Clinical Oncology (ASCO) and the European Cancer Conference (ECCO)
Selection of the trials
480 articles were identified from the literature research, from which 272 trials were initially considered ineligible for various reasons (194 were reviews, 11 were editorials/letters/lectures, 3 were case reports, and 64 studied prognostic factors or others) after browsing titles and abstracts (Fig. 1). 208 potentially relevant trials had the full text retrieved for a more detailed evaluation. Among these, 193 trials were secondarily excluded. 77 articles were considered ineligible for the
Discussion
Even after complete pathological resection, the majority of patients with pancreatic adenocarcinoma relapsed and died from their disease within five years. Sener et al. [27] assessed data from the National Cancer Database with over 100,000 PAC patients and found that only 9% of patients were resectable and that the best five-year overall survival rate observed for the patients who had a resection was only 23.4%. During the past 20 years, numerous clinical trials have been conducted to improve
Conclusion
In conclusion, this analysis demonstrated a significant benefit with regard to DFS and median OS for adjuvant chemotherapy after PAC resection. These results, however, do not support the use of adjuvant radiotherapy for PAC.
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgements
This work was supported by Leading Academic Discipline Project of Shanghai Municipal Education Committee, Project Number: J50208, Shanghai Municipal Natural Science Foundation, Project Number: 09ZR1417900, Shanghai Pujiang Program (11PJ1406500) and National Natural Science Foundation of China (81102015).
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Cited by (27)
Chemoradiotherapy after curative surgery for locally advanced pancreatic cancer: A 20-year single center experience
2021, Surgical OncologyCitation Excerpt :Accordingly, retrospective analyses from two high-volume centers in the US utilizing a more appropriate radiation dose and schedule than in the before mentioned trials, found an overall survival benefit after CRT versus observation alone [11,12]. When looking at aggregate data, two meta-analyses of 15 and 9 prospective studies, respectively, did not show any improvement in OS or DFS by adding radiation to adjuvant CT [13,14]. On the contrary, an outcome analysis of the National Cancer Data Base on patients undergoing surgery for PAC between 1998 and 2002 showed a huge survival advantage of adjuvant CRT over CT alone or observation [15].
Multimodal treatment of resectable pancreatic ductal adenocarcinoma
2017, Critical Reviews in Oncology/HematologyCitation Excerpt :Two meta-analyses (the first on 5 randomized trials including 939 patients; the second on 4 randomized trials including 875 patients) did not reveal any significant clinical benefit from the use of CRT, with a small survival benefit favoring the adoption of adjuvant CRT for patients who reported an R1 resection (Stocken et al., 2005; Butturini et al., 2008). Ren et al. conducted another meta-analysis on 15 randomized trials on adjuvant therapy and observed that, compared to observation, chemotherapy improved DFS and OS while CRT did not (Ren et al., 2012). Similarly, Liao et al. performed a meta-analysis on 9 randomized trials (3033 patients) to directly compare adjuvant CRT to chemotherapy (Liao et al., 2013).
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These two authors contribute equally to the work.