Pancreatic Cancer – Low Survival Rates: In Reply

by Prof. Dr. med. Dr. h. c. Hans G. Beger, PD Dr. med. Bettina Rau, PD Dr. med. Frank Gansauge, Dr. med. Gerd Leder, PD Dr. med. Michael Schwarz, PD Dr. med. Bertram Poch in volume 14/2008

It was an essential aim of the article "Pancreatic Cancer - Low Survival Rates" to describe the levels of dissemination of the carcinoma and the possibilities of surgical resection. There is no general agreement on what constitutes early pancreatic carcinoma. 30-40% of patients with advanced ductal pancreatic carcinoma exhibit infiltration of the lymph nodes in the aorto-caval compartments (1). In 35-60% of cases, the carcinoma extends into the extrapancreatic neural plexus.

The UICC protocol for the R-classification of pancreatic carcinoma provides only an inadequate description of the actual residual tumor status, based on the evaluation of four cut edges of the tumor.

After systematic evaluation of the resection borders, the frequency of R1 resection rose from 15-30% to clearly more than 50% (2).

If lymph node resection only incorporates the local lymph nodes, but not the extracorporal neural plexus, many patients retain residual tumor distant from the resection borders, in spite of the R0 resection according to the UICC protocol. This is the reason that only 10% of patients survive 5 years after R0 resection (observed survival).

The ESPAC-I study from the "European Study Group of Pancreatic Cancer" has shown for the first time that adjuvant chemotherapy provides a survival benefit in comparison with resection. This study has a large number of cases and a high level of evidence. The 5-FU bolus protocol of the ESPAC study was explicitly not addressed and not raised to the level of the standard treatment. Gemcitabine is currently the first line chemotherapy for advanced pancreatic carcinoma. On the other hand, the median survival advantage after gemcitabine monotherapy is unsatisfyingly low at 5 to 6 months and the partial response rate has the very low value of between 5.4% and 14.3% (3).

There are prospective study results and metaanalyses on the efficacy of palliative radiochemotherapy after R1/R2 resection. Stocken's metaanalysis concluded that adjuvant radiochemotherapy has greater efficacy than chemotherapy alone after R1 resection (4). Khanna's meta-analysis has shown that adjuvant, additive radiochemotherapy gives a survival benefit of 12% after two years (5). In the USA, palliative radiochemotherapy ("chemoradiation") has become the standard therapy after R1/R2 resection. DOI: 10.3238/arztebl.2008.0656


Prof. em. Dr. med. Dr. h. c. Hans G. Beger
Zentrum für Onkologische, Endokrinologische und
Minimalinvasive Chirurgie
Silcherstr. 36
89231 Neu-Ulm, Germany
[e-mail]

Conflict of interest statement
Professor Beger is founder and chair of the German German Pancreatic Cancer Foundation, c/o Ulm University Hospital. He initiated ESPAC and as such he patriciated in the ESPAC I study.

References

1. Beger HG, Gansauge F, Birk D: Pancreatic cancer: Lymph node dissection. In: Cameron JL (ed): Atlas of Clinical Oncology: Pancreatic Cancer. B. C. Decker, Inc. Ontario 2001, 123–32.

2. Esposito I, Kleeff J, Bergmann F et al.: Most pancreatic cancer resections are R1 resections. Ann Surg Oncol 2008;15: 1651–60.

3. Heinemann V: Present and Future Treatment of Pancreatic Cancer. Semin Oncol 2002; 29: 23–31.

4. Stocken DD, Büchler MW, Dervenis C et al: Meta-analysis of randomized adjuvant therapy trials for pancreatic cancer. Br J Cancer 2005; 92: 1372–81.

5. Khanna A, Walker GR, Livingstone AS, Arheart KL, Rocha-Lima C, Koniaris LG: Is adjuvant 5-FU-based chemoradiotherapy for resectable pancreatic adenocarcinoma beneficial? A meta-analysis of an unanswered question. J Gastrointest Surg 2006; 10: 689–97.