Pancreatic cancer is among the most challenging solid tumors to treat. In a majority of patients, the disease has locally spread to nearby organs at the time of diagnosis which makes its effective management a challenge. Moreover, the treatment itself causes a variety of complications that further decrease the survival time.
A recent study has provided more insights as to how exactly the current treatment of pancreatic cancer causes complications and leads to reduced survival of the patient. This blog post reviews the methodology and evidence presented in the study and draws clinical implications from the results.
Current challenges in the management of pancreatic cancer
Pancreatic cancer is an aggressive type of cancer that results from uncontrolled multiplication of the cells in the pancreas. The standard of care management includes surgical resection of the affected part of the pancreas and nearby parts of the body as well as chemotherapy [1]. However, pancreatic resection is technically challenging and results in postsurgical complications in as much as half of the patients [2].
Some of the complications are:
Pancreatic fistula (leakage from the pancreas)
Biliary leakage
Leakage of the gastrojejunostomy
Delayed gastric emptying
Pneumonia (lung infection)
These complications can lead to sepsis (spread of infection in the body), severe bleeding, organ failure, and even death [3]. Moreover, they affect an individual’s ability to receive adjuvant (after surgery) chemotherapy. Similar complications are well established as direct contributors to poor survival in other types of cancers such as colorectal, esophageal, and gastric cancer. However, their impact on pancreatic cancer is not fully understood.
Pancreatic cancer complications study
A nationwide, observational cohort study was performed in the Netherlands to assess the surgery-related complications in pancreatic cancer. It enrolled all patients undergoing resection for pancreatic cancer between 1 January 2014 and 31 December 2017 [4]. Only those patients were excluded who:
died within 90 days after surgery.
had metastatic disease at surgery.
received neoadjuvant treatment.
The researchers looked into the disease-free interval and overall survival as the primary outcomes of this study. The disease-free interval was defined as the time from surgery to diagnosis of recurrent disease or last follow-up. And the overall survival was defined as the time from surgery to death or last follow-up.
What was the outcome?
A total of 1278 patients underwent resection for pancreatic cancer. After excluding those who did not meet the criteria, 1071 patients were enrolled in the study. Adjuvant chemotherapy was administered to 61.9% of these patients. The median (middle value) overall survival of the patients after undergoing surgical removal of pancreatic cancer was 20 months. Some noteworthy postsurgical complications found by this study are given in the table below.
Complication | Occurrence |
Delayed gastric emptying | 12.1% |
Pancreatic fistula | 7.7% |
Pneumonia | 7.1% |
Hemorrhage | 4.7 |
Table 1: Complications arising after the surgical resection of pancreatic cancer.
Major complications after pancreatic cancer surgery and organ failure lowered median overall survival to 18 months compared to 22 months without complications. While individual complications did not significantly impact overall survival or disease-free interval, major complications as a group negatively affected the outcome. This was due to major complications resulting in less adjuvant chemotherapy being administered. Further analysis showed the harmful effect of major complications was fully explained by reduced adjuvant chemotherapy. Organ failure also decreased overall survival, both directly as well as indirectly by leading to less adjuvant treatment after surgery.
What are its implications?
This observational study demonstrated that major complications including organ failure following pancreatic cancer surgery were linked to poor disease-free and overall survival. The harmful impact of major complications on survival seemed to be explained by patients receiving less adjuvant chemotherapy. Additionally, the association between organ failure and decreased survival was partially attributable to fewer patients receiving adjuvant chemotherapy.
Furthermore, this study highlights the importance of strategic patient selection for neoadjuvant therapy (before surgery) in pancreatic cancer. Implementing more discerning criteria to identify patients likely to derive the greatest benefit from preoperative treatment could improve long-term prognosis after tumor resection.
References
1. H. M. Kolbeinsson, S. Chandana, G. P. Wright, and M. Chung, “Pancreatic Cancer: A Review of Current Treatment and Novel Therapies,” J Invest Surg, vol. 36, no. 1, p. 2129884, Dec. 2023, doi: 10.1080/08941939.2022.2129884.
2. R. P. Jones et al., “Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial,” JAMA Surg, vol. 154, no. 11, pp. 1038–1048, Nov. 2019, doi: 10.1001/jamasurg.2019.3337.
3. T. Keck et al., “Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial,” Ann Surg, vol. 263, no. 3, pp. 440–449, Mar. 2016, doi: 10.1097/SLA.0000000000001240.
4. A. C. Henry et al., “Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy: nationwide, observational cohort study,” BJS Open, vol. 7, no. 2, p. zrac174, Mar. 2023, doi: 10.1093/bjsopen/zrac174.
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