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Prediction Model for Adjuvant Radiation Therapy for Gallbladder Cancer: Not Ready to Be Used

Fundacion Oncologica Rodriguez Alzola, Salta, Argentina

Gaston Lemoine

Instituto de Radiaciones Salta S.A., Salta, Argentina

To the Editor:

Dr Wang et al¹ are to be commended for building a prediction model for the use of adjuvant radiation therapy (ART) in a population of 4,180 patients with gallbladder cancer (GC). This number far exceeds other published series of GC, which rarely include more than 100 patients. However, the prediction model they developed lacks one the most important prognostic and staging variables for GC: type of surgery. The analysis is based on patients for whom surgery with curative intention had been performed. Most patients with GC are first seen with unresectable disease² and the majority who undergo curative surgery have incidental findings in the pathology report. These patients usually have undergone a simple cholecystectomy (mainly laparoscopic).

The current recommendation for this scenario (except for the rare patient with stage T1 disease, where the recommended procedure is under discussion) is to re-operate to perform an extended or radical cholecystectomy (starting with examination of peritoneum and lumbo-aortic lymph nodes; if negative, perform a regional lymphadenectomy and resection of part of the liver adjacent to the gallbladder, and excise laparoscopic port sites).² This aggressive approach, which has a 2% to 5% mortality rate, is based on the fact that for stage T2 lesions (invasion without penetration of serosa), lymph node spread occurs in 48% of patients^3,4; for stage T3 lesions (perforation of serosa or direct invasion to liver and/or one adjacent organ) node spread occurs in 72% of patients ⁴; for stage T4 (invasion of major vessels or multiple extrahepatic organs) node spread occurs in 80% of patients.⁴ Though not shown in a randomized trial (which is difficult to accomplish in this disease), it is likely that compared with a radical cholecystectomy, a simple cholecystectomy leaves patients at a lower stage (understaging) and decreases the chance of survival.^5,6 Given that 60% of the 4,180 patients analyzed by Wang et al¹ had stage T3 or more advanced lesions and only 22% had known positive lymph nodes, many simple cholecystectomies were probably used as the sole surgical treatment.

Other evidence of the high percentage of nonradical cholecystectomies is the 5-year overall survival rate of 17% reported by Wang et al, contrasting with the expected 5-year overall survival rates of 40% after curative resection.^4,5 Incomplete staging could explain why ART was used in only 18% of patients. If radical cholecystectomy had been performed in patients initially treated with simple cholecystectomy, a high percentage of lymph node–negative cancers would have been upstaged and patients would have received ART, and the survival curves comparing patients treated with or without ART would have been closer to overlapping (due to the benefit of ART to lymph node–positive-upstaged patients, leaving the group of patients treated without ART with the only the true lymph node–negative cancers). In summary, excluding type of surgery in the prognostic model (the data were probably not available) is a serious limitation that weakens the strength of the prediction model and suggests it should not be used until type of surgery is included.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Wang SJ, Fuller D, Jong-Sung K, et al: Prediction model for estimating the survival benefit of adjuvant radiotherapy for gallbladder cancer. J Clin Oncol 26:2112-2117, 2008[Abstract/Free Full Text]

2. Weber S, O`Reilly EM, Abou Alfa GK, et al: Liver and bile duct cancer, in Abeloff MD, Armitage JO, Niederhuber JE, et al (eds): Clinical Oncology. Philadelphia, PA, Elsevier Churchill Livingstone, 2004, pp 1997-1999

3. Bartlett DI, Fong Y, Fortner JG, et al: Long term results after resection for gallbladder cancer: Implications for staging and management. Ann Surg 224:639-646, 1996[CrossRef][Medline]

4. Tsukada K, Hatakeyama K, Kurosaki I, et al: Outcome of radical surgery for carcinoma of the gallbladder according to the TNM stage. Surgery 120:816-821, 1996[CrossRef][Medline]

5. Fong Y, Jarnagin W, Blumgart LH: Galbladder cancer: Comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Ann Surg 232:557-569, 2000[CrossRef][Medline]

6. Shirai Y, Yoshida K, Tsukada K, et al: Inapparent carcinoma of the gallbladder: An appraisal of radical second operation after simple cholecystectomy. Ann Surg 215:326-331 1992[Medline]

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