Treatment of pancreatic cancer: challenge of the facts

Abstract

Adenocarcinoma of the pancreas is associated with the worst survival of any form of gastrointestinal malignancy. In spite of the progress in surgical treatment, resulting in increasing resection rates and a decrease in treatment-related morbidity and mortality, the true figures of cure are even today below 3%. The dissemination of pancreatic cancer behind the local tissue compartments restricts the short-term (< 3 years) and long-term outcome for patients who have undergone resection. By histological evaluation, less than 15% of the patients undergoing R(0) resection have a pN(0) status, more than 60% suffer from lymph angiosis carcinomatosa, and more than 50% suffer extrapancreatic nerve plexus infiltration. Hematoxylin and eosin-negative lymph nodes were found to be cancer positive when reverse transcriptase polymerase chain reaction (RT- PCR) or immunostaining was applied to the HE-negative lymph nodes. Cancer of the uncinate process has a very poor prognosis because there are no early symptoms; vessel wall involvement occurs early and frequently; a high association of liver metastasis exists as well. Surgery offers a low success rate, but it provides the only chance of cure. Ductal pancreatic cancer is diagnosed in more than 95% of the cases in an advanced stage; potentially curative resection can be performed only in about 10%-15% of these patients. Major contributions of surgery to improved treatment results are the reduction of surgical morbidity--e.g., early postoperative local and systemic complications--and a decrease of hospital mortality below 3%-5%. In most recently published prospective trials, R(0) resection has been reported to result in an increase in short-term survival beyond that recorded for patients with residual tumor. However, R(0) resection fails to improve long-term survival. In many published R(0) series, standard tissue resection of pancreatic head cancer with the Kausch-Whipple procedure failed to include remote cancer cell-positive tissues in the operative specimen; e.g., N(2)-lymph nodes, nerve plexus, and perivascular extrapancreatic and retropancreatic tissues were not excised. Cancer recurrence after so-called R(0) resection with curative intent is frequently the consequence of cancer left behind. Thus, long-term survival (> 5 years) is observed in a very small group of patients, contradicting the published 5-year actuarial survival rates of 20%-45% for resected patients. The assessment of clinical benefit from surgical or medical cancer treatment should therefore be based on several end points, not only on actuarial survival. Publication of actuarial survival figures must include the number of observed (actual) survivals, the definition of the subset of patients followed after resection, and the total number of patients in the study group; anything less is misleading. In reporting pancreatic cancer treatment trial results after oncological resections, more convincing primary end points to evaluate treatment efficacy are median survival (in months), actual survival at 1-5 years, and progression-free survival (in months). In series with multimodality treatment, clinical benefit response as well as quality of life measurements using the EORTC Quality of Life index C30 (QLQ-C30) are of importance in evaluating survival data. Adjuvant treatment improves survival after oncological resection; however, the short-term and long-term benefit after adjuvant chemotherapy in R(0) as well as in R(1)-(2) resected patients has not yet been underscored by data from controlled clinical trials. The survival benefit (median survival time) of adjuvant chemotherapy or radiochemotherapy has been demonstrated to be 6-10 months. Therefore, after oncological resection of pancreatic cancer each patient should be offered adjuvant treatment. A neoadjuvant treatment protocol for pancreatic cancer, however, has not been established.