**8.1 Studies**

110 Cancer of the Uterine Endometrium – Advances and Controversies

additional risks posed by a systematic LND and the benefits of performing the surgery by

In a large retrospective study, Cragun et al. (2005) summarized the morbidities of LND by laparotomy. Two to three percent of patients had small bowel obstruction or ileus, deep vein thrombosis and lymphocysts requiring drainage. Patients undergoing PLND and PaLND required longer anesthesia time and hospital stay and had greater blood loss compared to those who had PLND alone. Up to 8% of patients had a wound infection. Chronic

Querleu et al. (2006) audited 1,000 patients who had a *laparoscopic LND*. Only 1.3% were converted to laparotomy. Intra- and early post-operative complication and lymphocyst formation rates were 2.0%(bowel complication 0.7%; urinary tract complications 0.5%; nerve

**7.1 RCTs comparing laparotomy to minimally invasive surgery for endometrial cancer**  In the LAP-2 study, an RCT carried out by the Gynecologic Oncology Group (GOG), 2,616 patients with endometrial carcinoma confined to the uterus were randomly assigned to laparoscopy or laparotomy (Walker, 2009). All patients had complete surgical staging including PLND and PaLND. Laparoscopic-assisted vaginal hysterectomy, total laparoscopic hysterectomy or robotic-assisted total laparoscopic hysterectomy was allowed. They found that laparoscopy resulted in similar intra-operative complications, fewer post-operative moderate or severe adverse events (14% versus 21% by laparotomy, p<0.0001), shorter hospital stay, less use of pain medication and quicker resumption of daily activities but required longer operating time. Twenty five percent of patients randomized to laparoscopy were converted to laparotomy. Patients at higher risk for a conversion to laparotomy were elderly (>63 years) and those with metastatic disease and a high BMI (17% in patients with a BMI of 25kg/m2, 26% with a BMI of 35kg/m2, 57%

In an Australian RCT (n=361), which also compared total laparoscopic hysterectomy with abdominal hysterectomy in early endometrial carcinoma, 52% of the patients had a pelvic or para-aortic lymphadenectomy. Only 2.4% of patients assigned to laparoscopy were converted to laparotomy. Patients who had laparoscopic surgery reported significantly greater improvement in QoL from baseline compared with those who had laparotomy, this difference persisted for up to 6 months after surgery. Operating time was significantly longer in the laparoscopy group (138 minutes [SD 43]) versus 109 minutes [SD 34]; p=0.001). Intra-operative adverse events were similar between groups (laparotomy 5.6% versus laparoscopy 7.4%]; p=0.53), but postoperatively, twice as many patients in the laparotomy group experienced adverse events of Grade 3 or higher (23.2% versus 11.6%; p=0.004). The authors concluded that QoL improvements from baseline during early and later phases of recovery, and the adverse event profile, favor laparoscopy over laparotomy for the

Other studies that investigated the feasibility of minimally invasive surgery (laparoscopy and robot-assisted surgery) in elderly and obese patients concluded that neither age nor BMI is a contraindication to minimally invasive procedures, as it is these patients who benefit the most (Boggess et al., 2008; Gehrig et al., 2008; Janda et al., 2010; Obermair et al.,

lymphedema of the lower limbs was observed in 2.5% (Abu-Rustum et al., 2006).

laparoscopy or robotic surgery.

injuries 0.5%), 2.9% and 7.1%, respectively.

with a BMI >40kg/m2).

treatment of Stage I endometrial cancer.

2005; Scribner et al., 2001).

The Postoperative Radiation Therapy in Endometrial Cancer (PORTEC) Trial randomized 715 patients with Stage IB (Grades 2 and 3) and with IC (Grades 1 and 2) endometrial cancer after standard surgery without PLND to observation or pelvic RT with 46 Gy. Although the five-year actuarial locoregional recurrence rates were 4% in the radiotherapy group and 14% in the control group (p=0.001, the overall survival rates were similar in the two groups: 81% (radiotherapy) and 85% (controls), p=0.31. Endometrial-cancer-related death rates were 9% in the radiotherapy group and 6% in the control group (p=0.37). Treatment-related complications occurred in 25% of radiotherapy patients and in 6% of the controls (p=0.0001). One third of the complications were Grade 2 or higher. Seven out of eight Grade 3 to 4 complications were in the radiotherapy group (2%). The observation that the higher incidence of locoregional recurrences in the control group is not reflected in the overall survival was explained by the post-relapse survival. Twenty-three out of 51 patients with a locoregional relapse died, of whom only seven died due to their locoregional recurrence. By contrast, 21 of 30 patients with distant metastases as first failure died, of whom 19 died from the metastases. Salvage treatment of vaginal relapse was often successful. After vaginal recurrence, the two-year survival rate was 79% in contrast to 21% after pelvic or distant relapse. At three years, the survival was 69% and 13%, respectively (p=0.001). As for the survival after first relapse by treatment arm, the survival rate was better for patients in the control group than for patients in the radiotherapy group (p=0.02). The authors concluded that post-operative radiotherapy in Stage 1 endometrial carcinoma reduces locoregional recurrence but has no impact on overall survival and that radiotherapy increases treatmentrelated morbidity. Therefore, a trade-off between the risk of locoregional recurrence and the survival rate after salvage treatment on the one hand, and the morbidity and cost of adjuvant pelvic radiotherapy on the other, has to be made for each subgroup of Stage 1 endometrial carcinoma. These findings further support the need for a systematic LND whenever possible for patients with intermediate or high risk of endometrial cancer.

#### **8.2 Conclusion**

Adjuvant radiotherapy cannot be substituted for a systematic LND in intermediate- and high-risk endometrial cancer patients.
