Originally published as JCO Early Release 10.1200/JCO.2009.23.9822 on October 5 2009

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Is It Safe to Treat Endometrial Carcinoma Endoscopically?

Department of Gynecologic Oncology, University Hospital Leuven, Leuven, Belgium

Worldwide, endometrial cancer is the seventh most common malignancy, but incidence rates differ among regions. In North America and Europe, it is the commonest cancer of the female genital tract and the fourth commonest cancer site following breast, lung, and colorectal cancer.¹ The treatment of endometrial carcinoma is primarily surgical in operable patients; in its most recent classification, the International Federation of Gynaecology and Obstetrics adopted a surgical staging system.² Surgical treatment includes obtaining peritoneal fluid or washings for cytology; total hysterectomy, which by definition includes the uterine cervix; and bilateral salpingo-oophorectomy. In selected cases, there is a place for omentectomy and a thorough retroperitoneal lymph node dissection.¹ The role of pelvic and para-aortic lymphadenectomy remains controversial, as no improved survival has been observed after performing lymphadenectomy in patients with endometrial carcinoma.^3–4 However, we and others have argued that there is still an indication to perform a comprehensive lymphadenectomy to select patients at high risk for pelvic side wall recurrence.⁵

Many patients with endometrial cancer present with comorbidities such as obesity, hypertension, and diabetes. Abdominal surgery therefore exposes them to increased risk of complications. Vaginal hysterectomy has been suggested as an attractive alternative for these patients, but this approach does not allow exploration of the abdominal cavity, peritoneal washing, and lymph node dissection.^6–7 Laparoscopic-assisted vaginal hysterectomy overcomes the previous limitations and was first reported by Childers et al⁸ Several authors reported on the feasibility and safety of the laparoscopic approach in early-stage endometrial cancer compared with conventional treatment,^9–18 while others demonstrated the safety of the procedure in an obese or elderly population.^19–21 Recently, robotic-assisted surgical staging and treatment of endometrial carcinoma has been suggested as a valuable alternative to open abdominal surgery.^22–23 Randomized studies on endoscopic surgical treatment of endometrial carcinoma have, hitherto, been scarce or small. In two recent meta-analyses,^24–25 it was concluded that laparoscopy resulted in fewer complications, less blood loss, and similar survival. However, in the meta-analysis of Palomba et al,²⁴ only 172 patients were randomly assigned to endoscopic treatment, and the follow-up was short.

In this issue of the Journal of Clinical Oncology, the largest randomized trial ever performed in endometrial carcinoma is reported.^26–27 The Gynecologic Oncology Group (GOG), in their LAP-2 study, randomly assigned 2,616 patients to laparoscopy or laparotomy. As expected, laparoscopy resulted in fewer postoperative moderate or severe adverse events, a shorter hospital stay, and a longer operative time. Surprisingly, as many as 26% of the patients randomly assigned to laparoscopy were converted to laparotomy. Failure to complete laparoscopy successfully was related to increasing age and body mass index. This is unexpected, as many authors have claimed superiority of laparoscopy compared with laparotomy in obese patients.^19–21 The difference in conversion rates in obese and older patients observed in this large, multicentric LAP-2 study compared with reports from single institutions suggests that laparoscopic treatment might be more often successful in centers of excellence in laparoscopy or robotics. However, the recommendation of some authors^19–21 to perform laparoscopy in obese patients does not seem to be acceptable in the majority of centers in the LAP-2 study.

The number of pelvic lymph nodes removed in the LAP-2 study were similar for laparoscopy and laparotomy (median, 16 and 17, respectively), but the number of harvested para-aortic nodes was relatively low (6 and 7, respectively). It is noteworthy that the quality-of-life analyses did not show major significant differences between the two groups, and only modest differences in return to work (which disappeared 6 months after surgery) and body image. Unfortunately, no survival data have been reported yet. We encourage the authors to report on the survival and recurrence data, as this trial was initiated in 1996 and closed in 2005. We also question the value of routine lymphadenectomy in all patients with clinical stage IA-II endometrial carcinoma as performed in this study. Indeed, in the previous GOG study, it was shown that the incidence of pelvic lymph node metastases in well-differentiated tumors without or less than one-third myometrial thickness infiltration was as low as 0% and 1%, respectively.²⁸ Most of these patients can be identified on the basis of preoperative and peroperative examination and should not be exposed to the morbidity of an unnecessary lymphadenectomy.^1,16

In conclusion, the GOG is to be congratulated with this important report. The study confirms a longer operating time but reduced postoperative morbidity and shorter hospital stay following laparoscopy compared with laparotomy in endometrial carcinoma. However, we are all eagerly awaiting the relapse-free and overall survival rates and whether the sites of recurrence are similar in both surgical groups (eg, how frequently were port site and vaginal cuff metastases observed in the laparoscopy group?). As long as we do not have these data, we cannot make a final judgment on the safety of endoscopy as primary surgical treatment in endometrial carcinoma. Even if the survival and relapse outcomes were similar, we would need to evaluate carefully the advantages (eg, shorter hospital stay) and disadvantages (eg, longer operating time) and the effect of large volume/expertise on the treatment outcome, especially in older and obese patients.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

AUTHOR CONTRIBUTIONS

Conception and design: Ignace Vergote, Frederic Amant, Patrick Neven

Data analysis and interpretation: Ignace Vergote, Frederic Amant, Patrick Neven

Manuscript writing: Ignace Vergote, Frederic Amant, Patrick Neven

Final approval of manuscript: Ignace Vergote, Frederic Amant, Patrick Neven

NOTES

See accompanying articles on pages 5331 and 5337

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