Practice guidelines for management of cervical cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement

1-1. Generation of key questions based on PICO* [KQ 1] Are PET/ CT scans more sensitive than the CT or MRI in predicting lymph node metastasis for the treatment of cervical cancer? P : Cervical cancer I : PET C : MRI or CT O : nodal metastasis or lymph node metastasis 1-2. Medical literature search and study identification PubMed, EMBASE, and Cochrane were used for the literature search, and the search formula is as follows. Table 1. Procedure used for MEDLINE, EMBASE, and COCHRANE to identify eligible clinical trials for answering KQ1 MEDLINE 1. "Uterine Cervical Neoplasms"[Mesh] 59998 2.
Five articles were finally selected using aforementioned method.

## 1-3. quality assessment
Two non-randomized studies were finally selected and summarized in the table.

# 1-5. meta-analysis
There is insufficient evidence that PET/CT is more sensitive than CT or MRI to predict pelvic or para-aortic lymph node metastasis. PET/CT shows discrepant results in terms of sensititivity in selected studies for metaanalysis. As per the study protocol, CT, MRI, and PET/CT have different sensitivity, specificity, negative predictive value and positive predictive value. Overall, when metastases are not identified in the CT or MRI scans or when the results are uncertain, PET/CT could be helpful in predicting pelvic or aortic lymph node metastasis. Range of effect has been suggested by figures. PubMed, EMBASE, and Cochrane were used for the literature search, and the search formula is as follows. Four articles were finally selected using aforementioned method.

## 2-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below. The evidence for the key question was supported by the four NRS research results.
(Level of evidence: LOW)

# 2-5. meta-analysis
There is no randomized trial comparing laparoscopic or robotic surgery and open surgery. Based on the meta-analysis, relative risk reduction (RRR)=27%, event rate (ER)=7.4%, optimal information size (OIS)=600, and the number of death=50 is needed to have statistically significant results. This means that larger number of the study population is needed to clarify the differentiation in the death. From several retrospective studies, treatment outcome in terms of progression-free and overall survival is comparable between two groups. Laparoscopic or robotic radical hysterectomy can be performed in cervical cancer stage IB-IIA.

## Level of evidence: d (very low)
Strength

## 3-2. medical literature search and study identification
PubMed, EMBASE, and Cochrane were used for the literature search, and the search formula is as follows. Two articles were finally selected using aforementioned method. [fig_ref] Figure 1: Flow chart of searching strategy for answering KQ1 [/fig_ref]. Flow chart of searching strategy for answering KQ3

## 3-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below.

# 3-5. meta-analysis
Meta-analysis has been performed to investigate the survival outcome in early cervical cancer. Survival outcome after nerve sparing radical hysterectomy is similar to that of type III hysterectomy and results in decreased urinary difficulty. Based on the meta-analysis, relative risk reduction (RRR)=39%, event rate (ER)=6.8%, optimal information size (OIS)=200, and the number of death=5 is needed to have statistical analysis. One randomized trial and one non-randomized trial showed no impact of nerve sparing radical hysterectomy on survival outcome.

## Figure 2. result of meta-analysis

## 3-6. summary [kq 3] does the nerve sparing radical hysterectomy have similar survival outcome compared to type iii hysterectomy in early staged cervical cancer?
Nerve sparing radical hysterectomy could be performed in early staged cervical cancer.

## Level of evidence: c (low)
Strength of recommendation: 2 (weak)

## 3-7.
[ One article was finally selected using aforementioned method.

## 4-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below.

## 4-4. level of evidence and grade of recommendation
Page 17 The evidence for the key question was supported by the one RCT research results.
(Level of evidence: VERY LOW)
Page 18

# 4-5. meta-analysis
Although based on the limited study results including one prospective randomized trial, we do not observe the definitive loss of survival outcome from type I hysterectomy compared to radical hysterectomy in women with cervical cancer 2cm and type I hysterectomy shows better outcome for complication. Relative risk reduction (RRR)=62%, event rate (ER)=26%, optimal information size (OIS)=100, and the number of death=22
is needed for the near future prospective study.

## 5-2. medical literature search and study identification
PubMed, EMBASE, and Cochrane were used for the literature search, and the search formula is as follows. Three articles were finally selected using aforementioned method. [fig_ref] Figure 1: Flow chart of searching strategy for answering KQ1 [/fig_ref]. Flow chart of searching strategy for answering KQ5

## 5-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below. There is risk of bias related randomization and allocation concealment for the previous results. Relative risk reduction (RRR)=83%, event rate (ER)=50%, optimal information size (OIS)=50, and the number of death=7 is needed for the near future prospective study.

## 5-4. level of evidence and grade of recommendation

# 5-5. meta-analysis

## Figure 2. result of meta-analysis

## 5-6. summary [kq 5] does intensity modulated radiotherapy (imrt) result in less complications compared to standard radiotherapy in women with cervical cancer?
IMRT could be used as primary treatment for cervical cancer, based on the similar treatment outcome in terms of recurrence and survival with fewer complication rate.

## Level of evidence: c (low)
Strength of recommendation: 2 (weak)

## 5-7.
[

## 6-2. medical literature search and study identification
PubMed, EMBASE, and Cochrane were used for the literature search, and the search formula is as follows. One randomized trial result and 4 non-randomized studies were finally selected using aforementioned method. [fig_ref] Figure 1: Flow chart of searching strategy for answering KQ1 [/fig_ref]. Flow chart of searching strategy for answering KQ6

## 6-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below.

# 6-5. meta-analysis
Similar survival outcome has been observed between radical hysterectomy with selective adjuvant treatment and primary concurrent chemoradiotherapy in cervical cancer stage IB2 and IIA2. Althought the result of one randomized trial is not consistent to that of 4 non-randomized study, decrease of survival has not been observed in primary surgical group.

## 7-2. medical literature search and study identification
PubMed, EMBASE, and Cochrane were used for the literature search, and the search formula is as follows.

## 7-3. quality assessment
Page 32
The result of the evaluation of the the paper is summarized in the table below. The evidence for the key question was supported by the four NRS research results.
(Level of evidence: VERY LOW)

## 8-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below.

## 9-2. medical literature search and study identification
PubMed, EMBASE, and Cochrane were used for the literature search, and the search formula is as follows.

## 9-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below. One article was finally selected using aforementioned method.

## 10-3. quality assessment
The result of the evaluation of the the paper is summarized in the table below.
[fig] Figure 1: Flow chart of searching strategy for answering KQ1 [/fig]
[fig] Figure 4: Result of meta-analysis Does laparoscopic or robotic surgery have similar survival outcomes compared to open surgery for radical hysterectomy in cervical cancer stage IB-IIA? Medical literature search and study identification [/fig]
[fig] Figure 2: Result Does laparoscopic or robotic surgery have similar survival outcomes compared to open surgery for radical hysterectomy in cervical cancer stage IB-IIA? [/fig]
[table] Table 2: Study design characteristics based on the Ottawa Quality Assessment ScaleThe evidence for the key question was supported by the one NRS research result. [/table]
[table] Table 1: OR Cervical[tiab] OR "Signet Ring Cell"[tiab] OR Neuroendocrine[tiab] OR "Cervix Uteri"[Mesh] 237378 4. cancer[tiab] OR malignant[tiab] OR carcinoma[tiab] OR neoplasm[tiab] OR cancers[tiab] OR malignancy[tiab] OR carcinomas[tiab] OR neoplasms[tiab] 1749249 5. Adenocarcinoma[tiab] OR Adenocarcinomas[tiab] Adenosquamous[tiab] OR "Squamous Carcinoma"[tiab] OR "Squamous Carcinomas"[tiab] OR "Epidermoid Carcinoma"[tiab] OR adenocarcinoma'/de OR 'adenoid cystic carcinoma'/exp OR 'adenosquamous carcinoma'/exp OR 'clear cell carcinoma'/exp OR 'large cell carcinoma'/exp OR 'small cell carcinoma'/exp OR 'undifferentiated carcinoma'/exp OR 'endometrioid carcinoma'/exp OR 'signet ring carcinoma'/exp OR 'large cell neuroendocrine carcinoma'/exp 107895 3. cervix:ab,ti OR Cervical:ab,ti 235901 4. 'Signet Ring Cell':ab,ti OR Neuroendocrine:ab,ti OR cancer:ab,ti OR malignant:ab,ti OR carcinoma:ab,ti OR neoplasm:ab,ti OR cancers:ab,ti OR malignancy:ab,ti OR carcinomas:ab,ti OR neoplasms:ab,ti OR Adenocarcinoma:ab,ti OR Adenocarcinomas:ab,ti OR Adenosquamous:ab,ti OR 'Squamous Carcinoma':ab,ti OR [/table]
[table] Table 3: Evidence table [/table]
[table] Table 4: Estimation of GRADE [/table]