Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma

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Abstract

Aims

Despite curative surgery for pancreatic ductal adenocarcinoma (PDAC), most patients develop cancer recurrence and die from metastatic disease. Understanding of the patterns of failure after surgery can lead to new insights for novel therapeutic modalities. The aim of the present study is to describe the patterns of recurrence after curative resection of PDAC.

Methods

A retrospective analysis was performed of 145 consecutive resections for PDAC between 1998 and 2005 (M/F 75/70; median (range) age 67 years (32–85 y)). The location of the first and consecutive recurrences, and the time interval to cancer recurrence after surgical resection was studied. The magnitude of tumour-free margin was less than a millimetre in 48 patients, whereas a positive surgical margin was observed in 27 patients. The median duration of follow-up was 18.5 (range 0.3–116.8) months.

Results

Cancer recurrence was observed in 110 patients. The first location of recurrence was locoregional in 19, extra-pancreatic in 66, and combined locoregional and extra-pancreatic in 25 patients. Extra-pancreatic recurrence developed in the liver in 57, peritoneal in 35, pulmonary in 15, and retroperitoneal in 5 patients. The median (95% CI) overall (OS) and disease-free (DFS) survival was 18.7 (15.7–23.5) and 9.8 (7.5–12.4) months, respectively. The type of cancer recurrence did not significantly influence OS, while the resection margin status had a prognostic effect.

Conclusion

The vast majority of patients who undergo potentially curative surgery for PDAC develop cancer recurrence located in the abdominal cavity. Surgical resection margins with tumour involvement and tumour-free margins of less then 1 mm are negative prognostic factors. Further research on better local surgical control, peri-operative locoregional treatment, and more effective adjuvant systemic therapy is necessary to improve long-term survival of patients with curable PDAC.

Introduction

It remains a challenge to improve the survival of patients with pancreatic ductal adenocarcinoma (PDAC). The majority of patients present with locally advanced or metastatic disease and have a median survival of 6–8 months irrespective of the type of treatment modality.1 In selected patients (5–15%) with localised PDAC, surgical resection is the only treatment offering long-time survival.2 Despite the curative intent of surgical resection, cancer recurrence develops within two years after pancreatic surgery in over 60% of patients.3

Multiple studies have investigated the predictors of survival after surgery. However, only a few variables have been shown to correlate consistently with patient outcome. Surgical resection margin status and the presence of lymph node metastases were found to be most important determinants of survival after surgery for PDAC.2, 4, 5, 6 Although the majority of patients with PDAC die from distant metastatic disease, little is known about the exact pattern of cancer recurrence. The aim of the present study is to determine the first localization of cancer recurrence and the time interval to develop recurrence following curative resection of PDAC. A better understanding of the patterns of failure, i.e. where and when cancer recurrence occurs, could help develop novel and more rational therapeutic approaches.

Section snippets

Patients

Between January 1998 and December 2005, one hundred and forty-five patients with PDAC underwent surgical resection with curative intent. Patients with an intraductal papillary mucinous tumour (IPMT) were excluded from the study. The male/female ratio was 75/70, with a median age of 67 years (range 32–85 y). A standard pancreaticoduodenectomy (PD; n = 73) or a pylorus-preserving procedure (PPPD; n = 48) was performed in 121 patients for ductal carcinoma of the pancreatic head. Patients with PDAC of

Results

Median (range) duration of surgery was 258 (100–480) min, with a median intra-operative blood loss of 1100 (100–5000) ml. Postoperative complications occurred in 82 patients, with subsequent hospital mortality in 6 patients. Postoperative pancreatic fistula developed in 15 patients.

Discussion

In the present study, the recurrence rate after curative surgery for PDAC was 56.7, 76.6, and 84.1% at 1, 2, and 5 years, respectively. Over 90% of patients developed cancer recurrence in the abdominal cavity as being the first site of localization, either isolated or combined, in the liver (39%), locoregional (30%), or the peritoneum (24%). Pulmonary metastases occurred in about 10% of the patients and represented the most frequent site of extra-abdominal recurrence. Recurrence rates in the

Conclusion

After curative surgery for PDAC most patients develop locoregional and distant cancer recurrence, and survival rates remain low. The vast majority of patients develop cancer recurrence within the abdominal cavity. Surgical resection margins with tumour involvement (pR1) and tumour-free margins of less then 1 mm are negative prognostic factors. At present, adjuvant chemotherapy is the only adjuvant treatment with a small survival benefit, but really effective adjuvant treatment is lacking.

Conflict of interest

The authors have no conflict of interest.

Acknowledgements

Many thanks to the staff members of the departments of hepatobiliary and pancreatic diseases, digestive oncology, radiotherapy, and radiology for inclusion and follow-up of patients into this study; C. Verslype, E. Van Cutsem, K. Haustermans, D. Bielen, and D. Vanbeckevoort, respectively.

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