Browse Day: October 13, 2008

Clinical staging

A standardized system for the clinical and pathologic staging of pancreatic cancer does not currently exist in the United States. The system modified from the American Joint Committee on Cancer and the TNM Committee of the International Union Against Cancer appears in Table 32.4-4 (Table Not Available) . However, this staging system is rarely used because it is difficult to apply, the stages do not directly correlate with treatment or prognosis, and lymph node status cannot be determined without surgical treatment. Pathologic staging can be applied only to patients who undergo pancreatectomy; in all other patients, only clinical staging, based on radiographic examinations, can be done. Treatment and prognosis are based on whether the tumor is potentially resectable, locally advanced, or metastatic, definitions that do not directly correlate with TNM status. For example, both potentially resectable and locally advanced tumors may be stage T3. Further, because lymph node metastases are often small (2 to 4 mm) and not accurately assessed by preoperative imaging, many patients who undergo complete negative-margin pancreaticoduodenectomy are found to have positive regional lymph nodes on permanent-section pathologic analysis of the resected specimen. Such patients would then be classified as having stage III disease. However, a patient with unresectable, locally advanced disease is usually classified as having stage II (T3, N0) disease because operative (pathologic) staging is not performed.

Tumors of the pancreas are unlike other solid tumors of the gastrointestinal tract in that accurate diagnosis, clinical staging, and pathologic evaluation of resected specimens require extensive interaction and cooperation between physicians of different specialties. Accurate clinical staging requires high-quality computed tomography (CT) to accurately define the relationship of the tumor to the celiac axis and superior mesenteric vessels. The development of objective radiographic criteria for preoperative tumor staging allows physicians to develop detailed treatment plans for their patients, avoid unnecessary laparotomy in patients with locally advanced or metastatic disease, and improve resectability rates.
Similar standardized criteria are needed for the pathologic analysis of pancreaticoduodenectomy specimens to allow accurate interpretation of survival statistics.

 Retrospective pathologic analysis of archival material does not allow accurate assessment of margins of resection or number of lymph nodes retrieved. However, these are the most accurate predictors of outcome. In the recent study by Yeo and colleagues, resection margin, lymph node status, and tumor size and DNA content were the tumor characteristics that most strongly predicted survival by multivariate analysis. To determine which patient subsets may benefit from the most aggressive treatment strategies, accurate pathologic staging and histologic assessment of response are mandatory.

Natural history


Rational anticancer therapy for solid malignancies is based on an accurate knowledge of the natural history and patterns of treatment failure for each tumor type. Pancreatic cancer spreads early to regional lymph nodes, and subclinical liver metastases are present in the majority of patients at the time of diagnosis, even when findings from imaging studies are normal. Patient survival depends on the extent of disease and performance status at diagnosis. Extent of disease is best categorized as resectable, locally advanced, or metastatic. Patients who undergo surgical resection for localized nonmetastatic adenocarcinoma of the pancreatic head have a long-term survival rate of approximately 20% and a median survival of 15 to 19 months (Table 32.4-2) (Table Not Available) . As will be discussed, survival is clearly maximized by combining surgery with either preoperative or postoperative 5-fluorouracil (5-FU)-based chemotherapy and radiation therapy (chemoradiation). However, disease recurrence following a potentially curative pancreaticoduodenectomy remains common. Local recurrence occurs in up to 85% of patients who undergo surgery alone; local-regional tumor control is maximized with combined-modality therapy in the form of chemoradiation and surgery. With improved local-regional disease control, liver metastases become the dominant form of tumor recurrence and occur in 50% to 70% of patients following potentially curative combined-modality treatment.
Patients with locally advanced, nonmetastatic disease have a median survival of 6 to 10 months. A survival advantage has been demonstrated for patients with locally advanced disease treated with 5-FU-based chemoradiation compared with no treatment or radiation therapy alone. Patients with metastatic disease have a short survival (3 to 6 months), the length of which depends on the extent of disease and performance status.

Knowledge of the prognosis and patterns of treatment failure associated with adenocarcinoma of the pancreas leads to the following basic treatment principles:

The treatment must not be worse than the disease. The low cure rate and modest median survival following pancreatectomy mandate that treatment-related morbidity be low and treatment-related death be rare.

2.Improvements in patient survival and quality of life will result from the development of innovative treatment strategies directed at the known sites of tumor recurrence. Data to date have clearly demonstrated that as local-regional treatment becomes more effective, the dominant site of failure has shifted to hepatic metastases.

Therefore, future improvements in survival duration will result either from effective systemic or regional therapy directed at subclinical liver metastases or from strategies for screening and early diagnosis directed at increasing the number of patients eligible for potentially curative surgery. Future improvements in the quality of patient survival will result from the application of innovative multimodality therapy to carefully selected (staged) patients and the avoidance of unnecessary patient morbidity due to the inappropriate use of surgery, radiation, or chemotherapy or any combination thereof in poorly selected (advanced disease) patients.