Originally published as JCO Early Release 10.1200/JCO.2008.19.1999 on October 6 2008

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In Reply

Philippe Morice, Catherine Uzan, Enrica Bentivegna, Sebastien Gouy, Sophie Leboulleux, Martin Schlumberger, Christine Haie-Meder

Institut Gustave Roussy and University Paris Sud, Villejuif, France

We read with a great interest the letter by Kang et al concerning our recently published article. Kang et al add interesting data, reporting their own experience about the correlation between histology and positron emission tomography combined with computed tomography (PET-CT) in advanced stage cervical carcinoma. Among 24 patients reported with negative PET-CT imaging in the para-aortic area, two patients (8.3%) had histologically involved para-aortic nodes. This result is similar to those reported in our series, and seems to suggest that the false-negative rate of PET-CT imaging should be close to 10%.¹ As suggested by Kang et al and in our study, such results would justify including surgical staging in the para-aortic area to precisely define the level of chemoradiotherapy fields.^2,3 Furthermore, a recent article seems to demonstrate that this staging surgery improves the survival of patients with advanced-stage cervical cancer.² If such surgery is proposed, it should be performed using a laparoscopic approach to reduce the morbidity of this procedure, particularly if para-aortic radiation therapy is needed when and if patients are found to have histologic involvement of para-aortic nodes after such surgery.³

However, the question raised by Kang et al (should similar surgery be proposed in all cases of advanced stage cervical cancer with negative PET-CT imaging?) is of major concern because this surgical staging procedure requires teams that are experienced in laparoscopic para-aortic lymphadenectomy (to reduce the potential morbidity of the procedure), and not all patients managed for advanced cervical cancer have access to such staging surgery and additional chemoradiotherapy.

Kang et al propose that this staging surgery be performed in patients with PET-CT–positive pelvic nodes. In the experience they reported involving 24 patients with negative PET-CT imaging in the para-aortic area, 12 of them had uptake in pelvic nodes. The only two patients with false-negative results in the para-aortic area had uptake in pelvic nodes. This result suggests that this staging procedure should be reserved for patients with pelvic involvement. Staging surgery is indeed of particular interest in the subgroup of patients with uptake in pelvic nodes because nearly 25% of patients with positive (histologically proven) pelvic nodes will have involvement in the para-aortic area.⁴ However, PET-CT imaging in pelvic nodes is not as accurate as the histologic analysis of pelvic nodes, because we know that patients with pelvic nodal disease measuring less than 5 mm would have "normal" PET-CT imaging, given the current limits of this technique. These patients would therefore also have an increased risk of para-aortic spread.

In the experience reported by Loft et al,⁵ among 15 patients with uptake in the para-aortic area (12 of whom had a histologic analysis of this site), 13 patients (87%) also had PET-CT uptake in pelvic nodes. This means that 13% of these patients had no uptake in pelvic nodes. Our own series was recently updated to April 2008 to present our results in an international meeting. Until then, 54 patients with stage IB2/III disease had undergone initial PET-CT imaging demonstrating negative uptake in the para-aortic area followed by para-aortic lymphadenectomy. Nine of these patients had initial laparoscopic staging before chemoradiotherapy. Six patients (11%) had false-negative PET-CT imaging results. Among these six patients with false-negative results, two had no uptake in pelvic nodes.⁶

The presence of an isolated para-aortic area (without pelvic nodal spread) is a rare event in all patients with cervical cancer (in early- or advanced-stage disease), and was estimated to occur in nearly 1% of all patients.^4,7,8 However, in the case of a selected group of patients with locally advanced-stage disease, this risk is somewhat different. In our institution, between 1985 and 1995, 187 women with a bulky ( 4 cm) stage IB and II cervical carcinoma underwent radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy.⁴ Among those patients, 66 (35%) had positive nodes and 21 (11%) had para-aortic node involvement. Three of these 21 patients (15%) with a tumor size 4 cm and positive para-aortic nodes had isolated para-aortic lymph node involvement.⁴ Thus, in this subgroup of patients with a tumor size 4 cm, the risk of the tumor spreading directly to para-aortic nodes is not anecdotal. Posterior cervical lymphatic trunk drainage of lymph directly from the cervix into the para-aortic lymph nodes could account for these cases.⁹

As suggested by Kang et al, we think that staging surgery is of particular interest in the subgroup of patients whose disease stage is IB2 and who exhibit uptake in pelvic nodes (with uptake outside the pelvis) during initial PET-CT imaging, because the rate of para-aortic involvement is high. However, even if there is no uptake in pelvic nodes, this staging surgery in the para-aortic area should be maintained for two reasons: PET-CT imaging may fail to detect histologically involved pelvic nodes, and isolated spread directly to para-aortic nodes (without pelvic involvement) is not so infrequent in locally advanced cervical cancer. However, as suggested by Kang et al, additional studies are warranted to evaluate the economic impact of such staging surgery and patient access to such a procedure.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

ACKNOWLEDGMENTS

We thank Lorna Saint Ange for manuscript editing assistance.

NOTES

published online ahead of print at www.jco.org on October 6, 2008

REFERENCES

1. Boughanim M, Leboulleux S, Rey A, et al: Histologic results of para-aortic lymphadenectomy in patients treated for stage IB2/II cervical cancer with negative [18F]florodesoxyglucose positron emission tomography scans in the para-aortic area. J Clin Oncol 26:2558-2561, 2008[Abstract/Free Full Text]

2. Gold MA, Tian C, Whitney CW, et al: Surgical versus radiographic determination of para-aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma: A Gynecologic Oncology Group Study. Cancer 112:1954-1963, 2008[Medline]

3. Leblanc E, Narducci F, Frumovitz M, et al: Therapeutic value of pretherapeutic extraperitoneal laparoscopic staging in locally advanced cervical carcinoma. Gynecol Oncol 105:304-311, 2007[CrossRef][Medline]

4. Michel G, Morice P, Castaigne D, et al: Lymphatic spread of stage IB/II cervical carcinoma: Anatomy and surgical implications. Obstet Gynecol 91:360-363, 1998[CrossRef][Medline]

5. Loft A, Berthelsen AK, Roed H, et al: The diagnostic value of PET/CT scanning in patients with cervical cancer: A prospective study. Gynecol Oncol 106:29-34, 2007[CrossRef][Medline]

6. Morice P, Bentivegna E, Uzan C, et al: False results of PET-CT scan imaging in the para-aortic area and impact of para-aortic staging lymphadenectomy in patients treated for locally advanced cervical cancer. J Clin Oncol doi:10.1200/JCO.2008.19.7707 (in press)[Free Full Text]

7. Deppe G, Lubicz S, Galloway BT, et al: Aortic node metastases with negative pelvic nodes in cervical cancer. Cancer 53:173-175, 1984[CrossRef][Medline]

8. Morice P, Sabourin JC, Pautier P, et al: Isolated para-aortic lymph node involvement in patients with stage IB/II cervical carcinoma. Eur J Gynaecol Oncol 21:123-125, 2000[Medline]

9. Buschbaum HJ: Extrapelvic lymph nodes metastases in cervical carcinoma. Am J Obstet Gynecol 133:814-424, 1979[Medline]

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