Survival after surgical management of pancreatic adenocarcinoma: does curative and radical surgery truly exist?

Abstract

Surgery for pancreatic cancer offers a low success rate but it provides the only likelihood of cure. Modern series show that, in experienced hands, the standard Whipple procedure is associated with a 5-year survival of 10%-20%, with a perioperative mortality rate of less than 5%. Most patients, however, will develop recurrent disease within 2 years after curative treatment. This occurs, usually, either at the site of resection or in the liver. This suggests the presence of micrometastases at the time of operation. Negative lymph nodes are the strongest predictor for long-term survival. Other predictors for a favourable outcome are tumour size, radical surgery and a histopathologically well-differentiated tumour. Adjuvant therapy has, so far, shown only modest results, with 5FU chemotherapy, to date, the only proven agent able to increase survival. Nowadays, the choice of therapy should be based on histopathological assessment of the tumour. Knowledge of the molecular basis of pancreatic cancer has led to various discoveries concerning its character and type. Well-known examples of genetic mutations in adenocarcinoma of the pancreas are k-ras, p53, p16, DPC4. Use of molecular diagnostics and markers in the assessment of tumour biology may, in future, reveal important subtypes of this type of tumour and may possibly predict the response to adjuvant therapy. Defining the subtypes of pancreatic cancer will, hopefully, lead to target-specific, less toxic and finally more effective therapies. Long-term survival is observed in only a very small group of patients, contradicting the published actuarial survival rates of 10%-45%. Assessment of clinical benefit from surgery and adjuvant therapy should, therefore, not only be based on actuarial survival but also on progression-free survival, actual survival, median survival and quality of life (QOL) indicators. Survival in surgical series is usually calculated by actuarial methods. If there is no information on the total number of patients and the number of actual survivors, and no clear definition of the subset of patients, actuarial survival curves can prove to be misleading. Proper assessment of QOL after surgery and adjuvant therapy is of the utmost importance, as improvements in survival rates have, so far, proved to be disappointing.