Neoadjuvant Strategies for Pancreatic Cancer

The article entitled "NeoadjuvantStrategies for Pancreatic Cancer," by Drs. Evans, Wolff, and Crane, is an excellent review of past andcurrent developments in adjuvant therapy for pancreatic cancer. In addition to athorough literature review, the authors draw on their own extensive experiencein neoadjuvant therapy for pancreatic cancer at M. D. Anderson Cancer Center.

Adjuvant Therapy Dilemmas

The authors point out the pitfalls and unproven value ofpostoperative chemoradiation therapy, especially given that recurrence patternsin this setting usually reflect early disease dissemination. Until recently,systemic chemotherapy has not been a major emphasis of either pre- orpostoperative adjuvant therapy. This trend is changing. The current RadiationTherapy Oncology Group (RTOG) trial is randomizing resected patients to systemicchemotherapy first (fluorouracil [5-FU] or gemcitabine [Gemzar]) followed by5-FU-based chemoradiation. The European Study Group for Pancreatic Cancer(ESPAC) trial[1] (referred to by Dr. Evans and coauthors) has not yetdemonstrated a benefit for chemoradiation, but a trend favoring chemotherapy isemerging. Finally, the authors emphasize the importance of systemic therapy indescribing their future plans for neoadjuvant treatment (their Figure4).

Although it is clear that chemoradiation cannot be delivered toabout 25% of patients undergoing resection,[2]no randomized trial has provided evidence that the two approaches, neo vspostoperative adjuvant therapy, are therapeutically equivalent. As the authorsacknowledge, 25% of patients "progress through" neoadjuvant therapyand are no longer surgical candidates at the time of planned resection. As theauthors also point out, this phenomenon is important and averts the potentialmorbidity of surgery. However, it also underscores the need for "intent totreat" reporting of data with inclusion of all patients (resected or not),so that comparisons with existing data on postoperative adjuvant therapy can bemade.

Preoperative Therapy and Staging

The latter point is extremely important in assessing the benefitof neoadjuvant therapy that is administered with the intent of makingunresectable tumors resectable. Although this may be technically feasible, itmay not be wise. Even small (1 cm) pancreatic adenocarcinomas are associatedwith a high incidence of lymph node metastases.[3] Furthermore, as the authorsnote, the majority of treatment failures occur outside of the pancreatic bed(primarily in the peritoneum, liver, and lung). Thus, it may be wiser toconcentrate on more effective systemic therapy until we understand the truevalue of preoperative chemoradiation in patients with resectable disease.

Finally, the authors’ discussion of preoperative staging andmanagement is useful, thorough, and evidence based. However, one small point fordiscussion is the authors’ assertion that endoscopically guided fine-needleaspiration is now the procedure of choice for obtaining a tissue diagnosis priorto initiating therapy. While this is certainly a reliable approach, there are nocomparative data favoring this approach over a similar biopsy procedureperformed percutaneously under computed tomography (CT) guidance; CT-guidedbiopsies are both accurate and sensitive in this setting.[4]

Conclusions

In summary, this is an excellent review of the early managementof patients with potentially resectable pancreatic cancer, outlining thestrengths and weaknesses of our current strategies. Future clinicalinvestigation in this setting must focus on optimizing effective systemictherapy, understanding the true value of local radiation, and identifyingappropriate candidates for surgical resection.

References:

1. Neoptlemos J, Dunn J, Moffitt D, et al: ESPAC-1 interimresults: A European, randomized study to assess the roles of adjuvantchemotherapy (5-FU + folinic acid) and adjuvant chemoradiation (40 Gy + 5-FU) inresectable pancreatic cancer (abstract). Proc Am Soc Clin Oncol 19:238, 2000.

2. Spitz F, Abbruzzese J, Lee J, et al: Preoperative andpostoperative chemoradiation strategies in patients treated with pancreatic-oduoenectomy for adenocarcinoma of pancreas. J Clin Oncol 15:928-937, 1997.

3. Ishikawa O, Ohhigashi H, Sasaki Y, et al: Practicalusefulness of lymphatic and connective tissue clearance for carcinoma of thepancreas head. Ann Surg 208:215-220, 1988.

4. Athlin L, Blind PJ, Ångström T: Fine-needle aspirationbiopsy of pancreatic masses. Acta Chir Scand 156:91-94, 1990.