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Determining Optimal Routes to Surgery for Borderline Resectable Venous Pancreatic Cancer-Where Is the Least Harm and Most Benefit?

ABSTRACT: Surgery among patients with borderline resectable pancreatic cancer (BRPC) and venous disease has emerged as a viable strategy to achieve curative treatment. By definition, these patients are at increased risk of a positive resection margin, however, controversy exists with regards to necessity of radical surgery and optimum pathways with no consensus on definitive treatment. A surgery first approach is possible though outcomes vary but patients can have an efficient pathway to surgery, particularly if biliary drainage is avoided which limits overall complications. Neoadjuvant therapy (NAT) is emerging as a widely used strategy to improve oncological outcomes, including resection margin status. However, some patients progress on NAT whilst others suffer major complications whilst elderly patients are unlikely to be offered effective NAT limiting the widespread applicability of this therapy. In this article an overview of the entire pathway is presented along with assimilation of current best evidence to determine optimal routes to surgery for BRPC with venous involvement.

SUBMITTER: Pande R

PROVIDER: S-EPMC6811510 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Determining Optimal Routes to Surgery for Borderline Resectable Venous Pancreatic Cancer-Where Is the Least Harm and Most Benefit?

Pandé Rupaly R Roberts Keith J KJ

Frontiers in oncology 20191017

Surgery among patients with borderline resectable pancreatic cancer (BRPC) and venous disease has emerged as a viable strategy to achieve curative treatment. By definition, these patients are at increased risk of a positive resection margin, however, controversy exists with regards to necessity of radical surgery and optimum pathways with no consensus on definitive treatment. A surgery first approach is possible though outcomes vary but patients can have an efficient pathway to surgery, particul ...[more]

PMID: 31681596

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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:PurposePreoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.Patients and methodsIn this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.ResultsBetween April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096).ConclusionPreoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.

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Determining Optimal Routes to Surgery for Borderline Resectable Venous Pancreatic Cancer-Where Is the Least Harm and Most Benefit?

Publications

Determining Optimal Routes to Surgery for Borderline Resectable Venous Pancreatic Cancer-Where Is the Least Harm and Most Benefit?

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