Let's talk about the management of cervical cancer less than two centimeter. I don't like disclosures. So this is, as you all know, this is a FIGO staging. And as you can see here, for early and locally advanced cervical cancer, tumor size is one of the important factors in cervical cancer staging. So let's think about the principles of surgical resection. And safety margin is one of important principle when it comes to surgical oncology. And in terms of cervical cancer, we have actually several options of hysterectomy. So whether there is a microscopic disease, then we have con or simple hysterectomy, specifically stage 1A1. And 1A2, we can do modified radical hysterectomy. But 1B1 or above, we only do radical hysterectomy. So in this scenario, the size doesn't count at all. So one size fits all approach. So let's think about the two centimeters. So what does the less than two centimeter mean in cervical cancer? Overall, it means low risk of recurrence or death from the disease. So these are all retrospective data. So several authors suggested low risk criteria. And these criteria have a size limitation as two centimeter. So in this low risk group, when we think about the risk of parametric invasion, very surprisingly low, less than 1%. So when we add up all the numbers in this retrospective data, it's over 1,000 patient and parametric invasion is less than 1%. So if there are some patient who met this criteria, then we think of less radical surgery. But this is retrospective data. So, and in terms of lymph node metastasis, less than two centimeter means very low chance of node metastasis. So when we look at the stage 1A1, overall positive nodes is 1.2%. And 1B2, 3.2% is pretty low. But when we move on 1B, actually it is heterogeneous group, but in the textbook is said 70.3%. And recent analysis, 8,000 nodes were analyzed. And specifically this patient is 1B1, revised phagostage and 15.2%. So less radical hysterectomy will be feasible, but node assessment is very important. So in this setting, there were several attempts to try less radical surgery in this patient population. So in this study, their definition of low risk is less than two centimeter and less than half of stromal invasion based on MRI. And they first assessed the lymph node and further section shows that there is a negative node. Then they only do hysterectomy and parametrectomy, but this parametrectomy is not type 3 radical hysterectomy. So they just remove some soft tissue between the cervix and the nose. So it is less radical surgery. And then finally the nose were negative and then they did nothing. So on the right table, we can see the baseline characteristics and median age was 44 year old and more than half of patient had prior con and radical hysterectomy was done only 5%. And most of the patient have less radical surgery. It is close to a simple hysterectomy, but not exactly as the simple hysterectomy because they removed a small soft tissue of the parametrium, but less radical for sure. And as you can see here, recurrence was zero. Is it pretty good? Okay. And another study also shows the similar results. So first they did conjugation and based on the conjugation, the tumor is completely resected. And if patient want to preserve her fertility, then they didn't do hysterectomy, but they did pelvic node dissection and node was negative and the patient didn't have any adjuvant therapy. So right table shows the baseline characteristics of this study. And the median age was 35 year old and prior con 75% of patients and con was done almost in the half of the patient and simple hysterectomy was done in the rest of the patient. So as you can see here, recurrence was zero. So we can get an idea that we choose the right patient who are candidate for less radical surgery then simple hysterectomy or less radical surgery will be safe option. Another study also showed a similar result. So conserved study in the United States and lesser study in Brazil also showed a very low rate of recurrence or recurrence-free survival rate as compared to radical hysterectomy. So this is a unmet need for the less radical surgery. So because cervical cancer patient, about 40% of cervical cancer patient are young age and low risk and early stage. And as you can see here, so five-year survival rate is approximately over 40%, which is pretty good. But still we have done the same surgery of radical hysterectomy, which is associated with morbidity because resection of parametrium, which caused the injuries of the nerves, bladder dysfunction and sexual dysfunction and rectum dismobility. As I told earlier, those low risk group have a chance of less than 1% of parametrium invasion. So retrospect data and prospect for data also show the similar results showing the feasibility and safety of a lesser radical surgery, but we haven't had any phase three trial. And now this year, we know that we have a result of a SHAPE trial. So SHAPE trial is a international randomized phase three trial comparing radical hysterectomy versus simple hysterectomy. And their primary endpoint is pelvic recurrence rate at three years. And these are secondary endpoints. And this is definition in the SHAPE trial, which is low risk of cervical cancer. So in terms of histology, squamous, adenosquamous and adenocarcinoma were included, eligible. And FIGO stage 1A, 2 and 1B, 1. And on the con or lead biopsy, less than a one centimeter stroma invasion should be found. And on MRI, less than 50% of stroma invasion or maximal dimension of less than two centimeters. So if a patient who met this criteria, then a patient was randomized to either radical hysterectomy or simple hysterectomy. Let's look at the key baseline characteristics. So in terms of age, two groups are well balanced. And this is an interesting finding because when we look at the percentage of connigation prior con, then overall 84% in simple hysterectomy group had prior con as compared to 75.3% in radical hysterectomy. So I don't know if there is any statistical difference, but it's more patient had a connigation in simple hysterectomy. And why did patient in the simple hysterectomy group received more connigation than patient in the radical hysterectomy group? We don't know yet, but this is what it is. And in terms of stage, well balanced and histology was well balanced between two groups. In terms of type of surgical approach, more laparoscopic surgery was done in simple hysterectomy, which means more open surgery was done in radical hysterectomy. In terms of pathologic characteristics, it's a pretty well balanced except positive parametrium. So there's no positive parametrium in simple hysterectomy, but 1.7% in radical hysterectomy. So p-value was 0.03. Adjuvant treatment rate, less than 10% between two groups, well balanced. And recurrence rate is quite similar between two groups, recurrence pattern and death. So this is a primary endpoint. Three-year recurrence-free survival rate. Simple hysterectomy is 2.55% and radical hysterectomy is 2.1%. So difference is 0.35, which doesn't cross the 4%, which means that simple hysterectomy is not inferior to radical hysterectomy. So this is a primary endpoint. So this study met the primary endpoint. And three-year extra pelvic relapse-free survival are similar between two groups. And three-year overall survival are also similar between two groups. In the subgroup analysis, overall, we can see the non-inferiority of simple hysterectomy in every subgroup, except for the adenocarcinoma, but because of the relatively small size of this histology, so we can get a concrete result from this subgroup analysis. In terms of quality of life, for sure, simple hysterectomy is way better in all quality of life and sexual health issues. And in terms of surgical complication, surgery-related adverse events within four weeks was less in simple hysterectomy group, which was 42.6% versus 50%. So based on the SHAPE trial, it is definitely practice-changing results, but there are still some issues ongoing. So majority of the patient were squamous carcinoma, but we know that some portion of adenocarcinoma of the cervix are HPV-independent, and HPV-independent means worse survival. So do we apply this result to the small, but HPV-independent adenocarcinoma? We don't know yet. And in terms of patient selection, we need an MRI. So because the MRI criteria is quite important for patient selection, but what about low- or middle-income country where the MRI is not accessible or not quite available? And then do we need a congeniation to see the actual size or depth of invasion? We don't know yet. And the last issue is the MIS, because based on the LAC trial and National Cancer Data Base data registry analysis, we know they're less than two similar, even small tumor. There are some concern about the safety issue for MIS. So less than two centimeter, including the LAC trial in the meta-analysis show that MIS, radical hysterectomy, had worse PFS over survival. So still, even though less than two centimeter, they're still concerning about the laparoscopic approach or robotic approach. And once they occur, the more carcinomatosis was found in MIS group. So traditionally, when the early cervical cancer recur, who hadn't had radiation, then the local recurrence is salvageable. But the point is, when there is a recurrence from MIS, then there are more chance of carcinomatosis, which is not salvageable by radiotherapy. Conjugation issue. So because most of the clinical setting and the trial, the con was done for diagnostic purpose, not therapeutic purpose. But anyhow, after con, the survival was better. And when we see the LAC trial results, only focusing on the patient who had a con, then actually there's no difference between the MIS or the surgery. So, but it is hard to make a conclusion because the non-con group had more high-risk pathologic features, which might have contributed to the higher recurrence rate. So it's hard to understand how the con is affecting the overall outcome of patient who had a MIS or open surgery, but con will be one of the factors. And also some could argue that because of the worst outcome of MIS is because of the learning curve or surgical technique. So there are some clinical trials showing the safety of MIS with a specific technique, which to prevent the cervical, to prevent tumor split during the surgery, like trans-paternal closure or inter-corporate endoscopic stapling. But we have to see the final result of those studies. So this is the recent updated NCCN guideline. And another issue is that there are some times we see the incidental cervical cancer after hysterectomy. So if it is 1B1 or above, then we usually give them a definitive concurrent chemo radiation. But if the hysterectomy specimen met the criteria of a SHAPE trial, then we may skip the algebraic chemotherapy unless the lymph node was negative. So there are some options based on the SHAPE trial. And if the patient want to put to depreservation, then we know the user histology like a squousal carcinoma or adeno user type of adenocarcinoma. And less than two centimeter, then the patient could be a candidate for radical tracheotectomy. But if the tumor is less than two centimeter and meet the criteria of a SHAPE trial, then do we need radical tracheotectomy or we can go less, but we don't have any data because there is no clinical trial. So this is a little bit tricky situation. So this is my conclusion. So this is updated NCCN guideline, and there is a new blotted edit based on the SHAPE trial. So to perform MIS radical hysterectomy or a simple hysterectomy in early stage cervical cancer patients, it is necessary to evaluate not only the size of the tumor, but also the degree of a cervical stroma invasion on preoperative MRI very vigorously. And there are some issues about the MIS approach, but it is still debatable. Thank you for your attention.

cervical cancer

tumor size

hysterectomy

recurrence rates

surgical approach