Title : Surgical Simplification in Ovarian Cancer Treatment: A New Approach
The surgical removal of pelvic and retroperitoneal lymph nodes (LNR) is typically part of the surgical treatment for advanced epithelial ovarian cancers (AEO) which are highly lymphophilic tumors. Lymph node involvement is present in 61 to 78% of cases at advanced stages (FIGO III-IV). However, cytoreductive surgery alone is not sufficient, and the prognosis of these tumors has been significantly improved by platinum and taxane-based chemotherapy. The optimal strategy is complete primary surgery followed by at least 6 cycles of carboplatin-paclitaxel chemotherapy. But this may not always be possible after assessing resectability on imaging and during laparoscopy. In such circumstances, complete surgery is postponed in favor of 3-4 cycles of neoadjuvant chemotherapy, with the aim of reducing post-operative morbidity in patients whose general condition is often compromised at the time of diagnosis. Interval surgery is then performed followed by the remaining chemotherapy cycles. Pelvic and retroperitoneal lymph node removal is included in the resection surgery, but it can lead to specific serious complications (lymphoceles, chylous ascites, lymphedema, infections, urinary complications, hemorrhages) and reoperations. Its oncological benefit in terms of overall and progression-free survival has not been demonstrated in the absence of macroscopically suspicious nodes in the LION study comparing FIGO IIB-IV patients treated with primary surgery with and without LNR.
A randomized study in patients without suspicious nodes
A prospective European multicenter phase III study (CARACO) evaluated the benefit of LNR in the absence of suspicious lymph nodes both pre- and intraoperatively, in patients with FIGO II-IVA AEO randomized intraoperatively to LNR versus no LNR. The groups were stratified by surgical strategy (primary surgery and surgery after neoadjuvant chemotherapy). Surgery was always performed by laparotomy with visual and manual assessment of pelvic and retroperitoneal nodes. Surgical resection had to be complete if possible, but a residual < 1 cm was tolerated. The primary endpoint was progression-free survival (PFS). Between December 2008 and March 2020, 379 patients were randomized to a group with LNR (n = 181) and without LNR (n = 187), due to 11 secondary exclusions. The histological forms were serous or endometrioid adenocarcinomas in 87% of cases. The median number of lymph nodes in the LNR group was 28 (IQR = 19-36). Nearly half of the patients (43%) had at least one invaded node in the LNR group.Avoiding lymph node removal?
Neoadjuvant chemotherapy was necessary in 75% of patients, with 244 patients treated with 3 or 4 cycles before interval surgery and 41 patients treated with 6 cycles before delayed surgery. Primary surgery was performed in 83 patients followed by platinum-based adjuvant chemotherapy. The rate of surgery without residual disease was 86% and 88% respectively in the no LNR group and LNR group. Lymph node metastases were present in 49% of patients in the LNR group, with a median of 3 lymph nodes (IQR = 2-7). After a median follow-up of 9 years, the median PFS without LNR and with LNR was 14.8 months and 18.5 months, respectively (RR 0.98; 95% CI (0.78-1.22), p = 0.86). Median overall survival (OS) was not significantly different: 48.9 months and 58.0 months without LNR and with LNR, respectively (RR 0.96; 95% CI (0.75-1.22), p = 0.72). In subgroup analysis, PFS and OS were not different in the subgroup of patients who underwent complete surgery or neoadjuvant chemotherapy.Serious post-operative complications were more frequent in the LNR group, particularly in the first month with: re-laparotomies: 8.3% vs 3.1% (p = 0.031); urinary injuries: 3.8% vs 0.0% (p = 0.006); transfusions: 39.3% vs 29.7% (p = 0.049). Mortality within 60 days following surgery was similar between the groups: 1.1% vs 0.5% (p = 0.54) respectively. This trial confirms the data from the LION trial and extends its conclusions. Pelvic and retroperitoneal lymph node removal in the absence of suspicious nodes can be avoided in both primary cytoreductive surgery and interval surgery. This surgical simplification significantly reduces serious post-operative morbidity. The next step is to determine if LNR is beneficial in cases of suspicious nodes.