Jean-Marc Classe, MD, PhD, on Ovarian Cancer: New Data on Lymphadenectomy From the CARACO Trial

The CARACO trial is a trial about surgery for advance ovarian cancer patients. Advanced ovarian cancer patients are treated with complete surgery, with not residual, and the treatment could be primary surgery. If it is feasible to perform a primary complete surgery and then adjuvant chemotherapy, or if it's not possible, we can perform neoadjuvant chemotherapy, complete interval surgery. And then the other treatments. W. Hen you see some lymph nodes suspicious at the CT scan before surgery or during surgery, you must perform a lymphadenectomy. The question is not for this patient. The question is for patient with no suspicious lymph node at the CT scan before surgery or during surgery at the palpation of the peritoneum. And for this patient, you have already a study, a randomized study called the LION study. It was presented at the ESCO in 2017. The LION study was for primary surgery, advanced ovarian cancer patients with no suspicious lymph node treated by primary surgery. The LION trial demonstrates that it's not useful to perform an lymphadenectomy. So the remaining question is, what is the interest of lymphadenectomy for patients treated with neoadjuvant chemotherapy? And currently almost two thirds of the patients are treated with neoadjuvant chemotherapy. So it is an important question. So the CARACO trial, the design is inclusion criteria, epithelial ovarian cancer, primary treatments, no metastasis, but a FIGO stage three, no suspicious node at the CT scan before surgery. And a randomization complete surgery with lymphadenectomy compared with complete surgery with no lymphadenectomy. The results of this trial, if you consider just the morbidity, we observed statistically significant morbidity higher in the group of lymphadenectomy with more lymphedema, more re-intervention, more bleeding, transfusion, so more toxicity. The mortality rate was the same between the two arms, around 1 percent, no more. And if you consider the characteristics of the patients, you can observe a lot of complete surgery. 85 percent of complete surgery in both arms. In the lymphadenectomy arm we observed 28 median number of rejected lymph nodes, and 43 involvements, 43 involvements in the lymphadenectomy arm. And the significance is that these 43 lymph nodes involved remain in the patients in the new lymphadenectomy arm. And what is the result? To avoid a lymphadenectomy, the results of the CARACO trial is negative. What does it mean? It means that it's not useful to perform a lymphadenectomy in this patient with no suspicious lymph nodes before a treatment. So you are increasing the toxicity, but you're not increasing the survival. And it is true, for the primary endpoint, the disease-free survival, it is true for the secondary endpoint overall survival. And when you see subgroup analysis, you look at the results of the interval surgery, on the interval surgery, no difference. You look at the results of only high-grade serous carcinoma, no difference. So in conclusion, CARACO trial is a negative trial. So it means that for patients treated for an advanced ovarian cancer by primary surgery or neuro adjuvant chemotherapy, you don't have to perform a lymphadenectomy. We must talk about three limitations of the study. The first one is that we didn't include the right number of patients. We need 450 patients and we include a little less patients. But more important, we miss 22 events. We add only 320 events, and we missed 6 percent of the events required. But whatever happened to these 22 missing events, it is not possible that it could change the results. So we can say that the CARACO trial is a trial negative that demonstrates the not efficiency of the lymphadenectomy in the treatment of the patient with primary or with neuro adjuvant chemotherapy in case of no suspicious lymph nodes before surgery.