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Journal of Clinical Oncology, Vol 24, No 22 (August 1), 2006: pp. 3712-3713 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.06.7249
Sentinel Lymph Node Sampling and Analysis in Colon Cancer: What Is the Question?Institut Gustave Roussy, Villejuif, France To the Editor: Redston et al1 recently suggested that sentinel lymph node (SN) sampling (SNS) and analysis did not accurately predict the presence of either conventionally defined nodal metastasis or micrometastatic disease (MMD) in patients with resectable colon cancer. However, this multicenter study, which expanded previously reported results from the same team,2 presents several limitations. The authors reported on SNS performed in 72 patients with resectable colon cancer, who were recruited from 121 or 132 centers affiliated with the Cancer and Leukemia Group B. One should question whether all eligible patients referred to those 12 or 13 centers within the (unspecified) inclusion time period were actually included in this study, suggesting the possibility of patient selection bias. Moreover, the authors stated that "...each of the 25 surgeons were proficient in SN localization for breast cancer and malignant melanoma. In addition, before enrolling a patient on the study, each surgeon was coached by a single surgeon who was familiar with the SN localization technique for colon cancer."2 In fact, only two so-called high-volume surgeons performed 10 or more SNS (total, 21 patients), and the 18 low-volume surgeons performed less than five SNS (total, 20 patients).2 In a study of SNS in more than 4,000 patients with breast cancer, the surgeon's experience was the major factor that contributed to improve SNS yield, with a learning curve of approximately 20 patients3; a similar learning curve has been reported for colon cancer.4 Hence, one can question the accrual of so few colon cancer patients per surgeon, and the experience from breast cancer and melanoma may not be so easily transferable to that for colon cancer. Although this may represent real world practice, it may also at least partly explain the somewhat disappointing yield of SNS and analysis in this study. First, a 0% rate of SN located outside conventional resection margins contrasts with consistently reported 6%5 to 8%6 rates in previous multicenter studies. Second, an unusually low yield for multilevel sectioning (MLS; 1.2%) in identifying MMD leads the authors to suggest that SNS is useless if dedicated to concentrate pathologists' efforts to those SNs.1 Again, this figure is in discrepancy with those reported in previous studies, in which three to 10 sections of each SN were analyzed (five sections in the present study).7,8 For instance, we found a 15% yield of SNS and MLS in more than 120 colorectal cancer patients, meaning that 15% of N0 colorectal cancer patients can be upstaged to node-positive patients7,9 (unpublished observations). Of note, MLS allows the identification of MMD (or even SN macrometastases), the prognostic impact of which is far more clearly demonstrated than that of so-called occult metastases, which are detected only by immunohistochemistry (IHC) or molecular biology techniques.10 Finally, an unacceptably (as stated by the authors themselves) high false-negative rate (54%, or 12% with IHC) was observed, which again notably differed from previously reported figures (12% to 18% with standard histopathology, or 8% to 18% with IHC2,7 and even 0% in a multi-institutional study6).1 Using more stringent IHC criteria for defining MMD, the positive rate decreased from 70% to 38%, which is a figure more in accordance with the approximately 25% recurrence rate for stage II colon cancer11; this was also accompanied by a decrease in the false-positive rate, as assessed on benign colonic lesions.1 However, the false-negative rate concomitantly increased to 32%, leading the authors to consider that SNS, even with IHC, is not capable of replacing conventional regional lymph node staging. This assertion is misleading because the main interest of SNS likely relies on upgrading a subset of colon cancer patients staged as N0 (stage II) after conventional regional node histologic examination to node-positive (stage III) patients. Such upstaging could be obtained in approximately 15% of patients, as previously reported.5,7 Additionally, massive lymph node involvement is often associated with negative SN by diverting lymph flow via tumoral occlusion of lymphatic channels.5 As with breast cancer, it has been observed that the rate of positive SN decreases with advanced T stage in colon cancer,12 and colon cancers are generally bigger tumors than breast cancers, in which SNS is usually performed only in tumors less than 2 to 3 cm in size.13 Finally, the most important pitfall of this study is the wrong idea that is developed regarding the interest of SNS in colon cancer. Indeed, SNS technique can be assessed according to the following three directions: the first is certain: upstaging approximately 15% of N0 (stage II) colon cancer patients to node-positive (stage III) patients, which may ultimately lead to prescribed adjuvant chemotherapy and to a decreased recurrence rate, as recently suggested in a multicenter trial in which 7% of the 153 patients in the SNS group experienced recurrences at a minimum of 2 years of follow-up compared with 25% of the 162 patients in the control group14; the second is possible but unproven: detecting SN outside the conventional regional node basin; and the third is likely ineffective: replacing conventional regional lymph node staging. It seems that Redston et al1 favored the third direction. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Redston M, Compton CC, Miedema BW, et al: Analysis of micrometastatic disease in sentinel lymph nodes from resectable colon cancer: Results of Cancer and Leukemia Group B Trial 80001. J Clin Oncol 24:878-883, 2006 2. Bertagnolli M, Miedema B, Redston M, et al: Sentinel node staging of resectable colon cancer: Results of a multicenter study. Ann Surg 240:624-630, 2004[Medline] 3. Hutchinson JR, Chagpar AB, Scoggins CR, et al: Surgeon and community factors affecting breast cancer sentinel lymph node biopsy. Am J Surg 190:903-906, 2005[Medline] 4. Joosten JJ, Strobbe LJ, Wauters CA, et al: Intraoperative lymphatic mapping and the sentinel node concept in colorectal carcinoma. Br J Surg 86:482-486, 1999[CrossRef][Medline] 5. Saha S, Bilchik A, Wiese D, et al: Ultrastaging of colorectal cancer by sentinel lymph node mapping technique: A multicenter trial. Ann Surg Oncol 8:94S-98S, 2001 (suppl 9)[Medline] 6. Bilchik AJ, Saha S, Wiese D, et al: Molecular staging of early colon cancer on the basis of sentinel node analysis: A multicenter phase II trial. J Clin Oncol 19:1128-1136, 2001 7. Baton O, Lasser P, Sabourin JC, et al: Ex vivo sentinel lymph node study for rectal adenocarcinoma: Preliminary study. World J Surg 29:1166-1171, 2005[CrossRef][Medline] 8. Bilchik AJ, Giuliano A, Essner R, et al: Universal application of intraoperative lymphatic mapping and sentinel lymphadenectomy in solid neoplasms. Cancer J Sci Am 4:351-358, 1998[Medline] 9. Lasser P, Coté JF, Sabourin JC, et al: Intérêt de l'analyse du ganglion sentinelle pour les cancers coliques: Etude de faisabilité. Ann Chir 128:433-437, 2003[CrossRef][Medline] 10. Noura S, Yamamoto H, Ohnishi T, et al: Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. J Clin Oncol 20:4232-4241, 2002 11. Jemal A, Tiwari RC, Murray T, et al: Cancer statistics, 2004. CA Cancer J Clin 54:8-29, 2004 12. Tsioulias GJ, Wood TF, Morton DL, et al: Lymphatic mapping and focused analysis of sentinel lymph nodes upstage gastrointestinal neoplasms. Arch Surg 135:926-932, 2000 13. Nano MT, Kollias J, Farshid G, et al: Clinical impact of false-negative sentinel node biopsy in primary breast cancer. Br J Surg 89:1430-1434, 2002[CrossRef][Medline] 14. Saha S, Seghal R, Patel M, et al: A multicenter trial of sentinel lymph node mapping in colorectal cancer: Prognostic implications for nodal staging and recurrence. Am J Surg 191:305-310, 2006[CrossRef][Medline]
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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