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Treatment of pancreatic cancer-neoadjuvant treatment in resectable pancreatic cancer (PDAC).

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Curative-intended resection and adjuvant chemotherapy represents the current standard of care. Despite substantial improvements in surgical treatment and intensified adjuvant treatment with more powerful regimens over the last years even clearly resectable pancreatic cancer still has an unfavorable prognosis with a high risk of relapse. Neoadjuvant or perioperative multimodal therapies have substantially improved the outcome of other resectable gastrointestinal (GI) cancers such as esophagus and gastric cancer. It is reasonable to assume that efficient chemotherapy and or radiochemotherapy may have a similar impact on the outcome of resectable PDAC. This review is focused on neoadjuvant and perioperative treatment of resectable PDAC (no borderline resectable or locally advanced PDAC), summarizes the pros and cons for neoadjuvant treatment in the context of the current literature, and also provides an overview over the landscape of ongoing clinical trials in this up-and-coming field of PDAC therapy.

SUBMITTER: Seufferlein T

PROVIDER: S-EPMC6458347 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Treatment of pancreatic cancer-neoadjuvant treatment in resectable pancreatic cancer (PDAC).

Seufferlein Thomas T Ettrich Thomas J TJ

Translational gastroenterology and hepatology 20190327

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Curative-intended resection and adjuvant chemotherapy represents the current standard of care. Despite substantial improvements in surgical treatment and intensified adjuvant treatment with more powerful regimens over the last years even clearly resectable pancreatic cancer still has an unfavorable prognosis with a high risk of relapse. Neoadjuvant or perioperative multimodal therapies have substantially improved the outc ...[more]

PMID: 30976724

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Project description:Approximately 20% of pancreatic ductal adenocarcinoma (PDAC) patients have (borderline) resectable pancreatic cancer [(B)RPC] at diagnosis. Upfront resection with adjuvant chemotherapy has long been the standard of care for these patients. However, although surgical quality has improved, still about 50% of patients never receive adjuvant treatment. Therefore, recent developments have focused on a neoadjuvant approach. Directly comparing results from neoadjuvant and adjuvant regimens is challenging due to differences in patient populations that influence outcomes. Neoadjuvant trials include all patients who have (B)RPC on imaging, while adjuvant-only trials include patients who underwent a complete resection and recovered to a good performance status without any evidence of residual disease. Guidelines recommend neoadjuvant treatment for BRPC patients mainly to improve negative resection margin (R0) rates. For resectable PDAC, upfront resection is still considered the standard of care. However, theoretical advantages of neoadjuvant treatment, including the increased R0 resection rate, early delivery of systemic therapy to all patients, directly addressing occult metastatic disease, and improved patient selection for resection, may also apply to these patients. A systematic review by intention-to-treat showed a superior median overall survival (OS) for any neoadjuvant approach (19 months) compared to upfront surgery (15 months) in (B)RPC patients. A neoadjuvant approach was recently supported by three randomized controlled trials (RCTs). For resectable PDAC, neoadjuvant treatment was superior in a Japanese RCT of neoadjuvant gemcitabine with S-1 vs. upfront surgery, with adjuvant S-1 in both arms (median OS: 37 vs. 27 months, p = 0.015). A Korean trial of neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront resection in BRPC patients was terminated early due to superiority of the neoadjuvant group (median OS: 21 vs. 12 months, p = 0.028; R0 resection: 52 vs. 26%, p = 0.004). The PREOPANC-1 trial for (B)RPC patients also showed favorable outcome for neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront surgery (median OS: 17 vs. 14 months, p = 0.07; R0 resection: 63 vs. 31%, p < 0.001). FOLFIRINOX is likely a better neoadjuvant regimen, because of superiority compared to gemcitabine in both the metastatic and adjuvant setting. Currently, five RCTs evaluating neoadjuvant modified or fulldose FOLFIRINOX are accruing patients.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is currently ranked fourth place of cancer related mortality. Only a minority of 10-20% of patients with PDAC have a primarily resectable disease, while 50-60% of the patients are diagnosed with irresectable disease. A certain group of patients is defined as "borderline resectable", which is mainly relied to contact of the tumor to major abdominal vessels. For preoperative evaluation of resectability CT and MRI is commonly used. Although CT-scanning, which is the standard preoperative imaging modality, has striking limitations concerning evaluation of lymph node status as well as vessel involvement and approximately 20% of the patients are staged incorrectly. A central part of modern therapy of locally advanced or not primarily resectable PDAC is neoadjuvant therapy. Especially neoadjuvant chemotherapy according to the FOLFIRINOX protocol resulted in high resection rates of initially not resectable patients. Furthermore, treatment with FOLFIRINOX was shown to be an independent predictor of improved prognosis and resection after neoadjuvant treatment with FOLFIRINOX was associated with improved survival. Neoadjuvant treatment was able to increases the rates of R0 resection, which depicts an independent prognostic factor and FOLFIRINOX outmatched other treatment regimes (e.g., gemcitabine-based radio-chemotherapy) concerning achievement of a R0 resection. While most evidence of neoadjuvant treatment of PDAC is conferred by retrospective analysis, there is growing data from randomized controlled trials, confirming the beneficial effects of neoadjuvant therapy on the prognosis of PDAC. Thus, patients with borderline resectable and locally advanced PDAC should be evaluated for neoadjuvant treatment. If there is no progression of the disease during neoadjuvant treatment exploration with the goal of R0 resection should be performed. If possible, patients should be included in well-designed randomized controlled trials at specialized pancreatic centers.

Dataset Information

Treatment of pancreatic cancer-neoadjuvant treatment in resectable pancreatic cancer (PDAC).

Publications

Treatment of pancreatic cancer-neoadjuvant treatment in resectable pancreatic cancer (PDAC).

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