Notable surgical trials in gynecologic oncology: a 10-year overview.

In the last decade, we have witnessed important advances in novel therapeutics in the management of gynecologic cancers. These studies have built on the findings from preexisting data and have provided incremental contributions leading to changes that have not only impacted the accuracy of cancer detection and its metastatic components but also led to improvements in oncologic outcomes and quality of life. Key landmark trials have changed the standard of care in cervix, uterine, and ovarian cancer. A number of these have been controversial and have generated significant debate among gynecologic oncologists. The main objective of this review was to provide an overview on each of these trials as a reference for immediate and consolidated access to the study aims, methodology, results, and conclusion.

LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of -11.1; 95% CI, -15.8 to -6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.

Association of reviewer experience with discriminating human-written versus ChatGPT-written abstracts.

OBJECTIVE: To determine if reviewer experience impacts the ability to discriminate between human-written and ChatGPT-written abstracts. METHODS: Thirty reviewers (10 seniors, 10 juniors, and 10 residents) were asked to differentiate between 10 ChatGPT-written and 10 human-written (fabricated) abstracts. For the study, 10 gynecologic oncology abstracts were fabricated by the authors. For each human-written abstract we generated a ChatGPT matching abstract by using the same title and the fabricated results of each of the human generated abstracts. A web-based questionnaire was used to gather demographic data and to record the reviewers' evaluation of the 20 abstracts. Comparative statistics and multivariable regression were used to identify factors associated with a higher correct identification rate. RESULTS: The 30 reviewers discriminated 20 abstracts, giving a total of 600 abstract evaluations. The reviewers were able to correctly identify 300/600 (50%) of the abstracts: 139/300 (46.3%) of the ChatGPT-generated abstracts and 161/300 (53.7%) of the human-written abstracts (p=0.07). Human-written abstracts had a higher rate of correct identification (median (IQR) 56.7% (49.2-64.1%) vs 45.0% (43.2-48.3%), p=0.023). Senior reviewers had a higher correct identification rate (60%) than junior reviewers and residents (45% each; p=0.043 and p=0.002, respectively). In a linear regression model including the experience level of the reviewers, familiarity with artificial intelligence (AI) and the country in which the majority of medical training was achieved (English speaking vs non-English speaking), the experience of the reviewer (ß=10.2 (95% CI 1.8 to 18.7)) and familiarity with AI (ß=7.78 (95% CI 0.6 to 15.0)) were independently associated with the correct identification rate (p=0.019 and p=0.035, respectively). In a correlation analysis the number of publications by the reviewer was positively correlated with the correct identification rate (r28)=0.61, p<0.001. CONCLUSION: A total of 46.3% of abstracts written by ChatGPT were detected by reviewers. The correct identification rate increased with reviewer and publication experience.

De-escalation of surgical radicality for non-fertility preserving management in patients with early-stage cervical cancer: a systematic review.

OBJECTIVE: We sought to evaluate the oncologic outcomes of simple hysterectomy in patients with low-risk early-stage cervical cancer (tumors ≤2 cm with limited stromal invasion). METHODS: This study was registered in PROSPERO (registration number CRD42023433840) following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist. MEDLINE (through Ovid), EmMBASEbase, and Cochrane Central Register of Controlled Trials were searched from inception until June 2023. Randomized controlled trials and observational studies with two arms of comparison (simple hysterectomy with lymph node assessment vs radical hysterectomy with lymph node assessment) in patients with low-risk early-stage cervical cancer were considered. RESULTS: The search identified 1270 articles; eighteen studies were considered potentially eligible after removing duplicates, and four met the selection criteria. Three studies were randomized controlled trials, and the other was a retrospective cohort study. In total, 981 patients were included. There were 485 (49.4%) and 496 (50.6%) patients in the simple hysterectomy and radical hysterectomy groups, respectively. Simple hysterectomy with lymph node assessment was not associated with a higher risk of death at 5 years (RR 0.98, 95% CI: 0.31 to 3.10; I2=0%, two randomized controlled trials, 141 patients, for an absolute risk reduction of zero percentage points [95% CI -9.0 to 9.0]), pelvic recurrence at 3 years (97.5% and 97.8% for simple hysterectomy and radical hysterectomy, respectively, p=0.79), and overall recurrence at 3 years (95 %% and 100% for simple hysterectomy and radical hysterectomy, respectively, p=0.30). CONCLUSION: Simple hysterectomy with lymph node evaluation for low-risk early-stage cervical cancer is not associated with a detrimental effect on oncologic outcomes and has a better morbidity profile.

Pelvic lymph node involvement and risk of recurrence in HPV-associated endocervical adenocarcinoma stage IA2-IB1 according to Silva's system in two Colombian cancer centers.

OBJECTIVE: To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system. METHODS: A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists. RESULTS: A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively. CONCLUSION: For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

Recurrence After Biopsy-Confirmed Cervical High-Grade Intraepithelial Lesion Followed by Negative Conization: A Systematic Review and Meta-analysis.

ABSTRACT: The aim of the study is to assess the recurrence rate (as cervical intraepithelial neoplasia 2+ [CIN2+]) in patients who had a confirmed high-grade squamous intraepithelial lesion (CIN2-3) in a cervical biopsy specimen followed by a negative conization specimen. MATERIALS AND METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Ovid/MEDLINE, Ovid/Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception until January 2023. The study protocol was registered in PROSPERO (ID number CRD42023393951). The search identified 3,089 articles; 1,530 were removed as duplicates, and 1,559 titles and abstracts were assessed for inclusion. The full text of 26 studies was assessed for eligibility, and finally, 12 studies with 1,036 patients were included. All included studies were retrospective cohort studies. A proportion meta-analysis was performed. RESULTS: For patients with negative conization specimens, the recurrence rate as CIN2+ during follow-up was 6% (95% CI, 1.8%-12.1%; I2 = 49.2; p < .0001, 215 patients and 4 studies) in the proportion meta-analysis, ranging from 0.3% to 13.0% for the individual studies. For patients with ≤CIN1 conization specimens, the recurrence rate as CIN2+ during follow-up was 3.6% (95% CI, 1.2%-7%; I2 = 75.1; p < .0001, 991 patients and 10 studies) in the proportion meta-analysis and ranged from 0.6% to 13.0% for the individual studies. CONCLUSIONS: The recurrence rate as CIN2+ for patients with a confirmed high-grade intraepithelial lesion on a cervical biopsy followed by a negative conization specimen is 6%. In patients with negative and CIN1 conization specimens, the recurrence rate is 3.6%.

Sentinel lymph node assessment in patients with atypical endometrial hyperplasia: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to assess the rate of sentinel lymph node (SLN) metastases in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia and endometrial cancer in hysterectomy specimens. METHODS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and the protocol was registered in PROSPERO (CRD42023416769). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2023. The inclusion criteria were patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia undergoing hysterectomy who did or did not undergo SLN assessment. RESULTS: Four studies met the inclusion criteria. All studies were non-randomized studies with a total of 10 217 patients, 1044 in the SLN group and 9173 in the non-nodal assessment group. The unilateral and bilateral detection rate was 89% (I2=27.6%, 2 studies, 342 participants, 304 events) and 79% (I2=89.2%, 2 studies, 342 participants, 271 events), respectively. The rate of involved SLNs was 1.6% (I2=0%, 3 studies, 424 participants, 7 involved SLN) and 3.5% (I2=0%, 3 studies, 197 participants, 7 involved SLN) in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia as the denominator and in those with endometrial cancer in the hysterectomy specimen, respectively. The cancer rate in the hysterectomy specimen was 45% (I2=72.8%, 3 studies, 503 participants, 224 events) and the most frequent endometrial cancer International Federation of Gynecology and Obstetrics 2009 stage was IA in 199 (89.2%) patients. The complication rate was similar between the groups. CONCLUSION: The rate of SLN metastases in patients with pre-operative atypical hyperplasia/endometrial intra-epithelial neoplasia is less than 2%, suggesting that routine SLN evaluation may not be necessary in this population.

Uterine transposition for fertility and ovarian function preservation after radiotherapy.

OBJECTIVE: To evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation. METHODS: This prospective multicenter observational study included patients with non-gynecologic pelvic cancers who underwent pelvic radiation as part of their cancer treatment between June 2017 and June 2019. For inclusion in the study, patients were required to have normal menstrual cycles and hormone levels (follicle-stimulating hormone, luteinizing hormone, and estrogen) before treatment. Uterine transposition to the upper abdomen was performed prior to irradiation. Clinical examinations and Doppler ultrasonography were used to evaluate the gonadal vasculature post-surgery. The uterus was repositioned into the pelvis 2-4 weeks after radiation therapy or at the time of rectosigmoid resection in patients with rectal cancer who had undergone neoadjuvant treatment. Cancer treatment and follow-up were performed according to standard guidelines. RESULTS: Eight patients (seven with rectal cancer and one with pelvic liposarcoma) underwent uterine transposition at a median age of 30.5 years (range 19-37). The uterus was successfully preserved in six patients, accompanied by normal menses, hormonal levels, and vaginal intercourse after treatment. One patient with rectal cancer died of carcinomatosis 4 months after uterine transposition. One patient presented with uterine necrosis 4 days after uterine transposition, and the uterus was removed; however, one ovary was preserved. Cervical ischemia was the most common post-surgical complication in three (37.5%) patients. Three patients attempted to conceive, and two (66%) were spontaneously successful and delivered healthy babies at 36 and 38 weeks by cesarean section without complications. CONCLUSIONS: Uterine transposition is a feasible procedure for preserving gonadal and uterine function in patients requiring pelvic radiotherapy for non-gynecological cancer, with the potential for achieving spontaneous pregnancy and successful delivery.

Complications of HIPEC for ovarian cancer surgery: evaluation over two time periods.

OBJECTIVE: Cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) is being explored in the upfront, interval, and recurrent setting in patients with ovarian cancer. The objective of this systematic review was to assess the rate of complications associated with HIPEC in epithelial ovarian cancer surgery over two time periods. METHODS: This study was registered in PROSPERO (CRD42022328928). A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Ovid/Medline, Ovid/Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials were searched from January 2004 to April 2022. We included studies reporting on patients with advanced primary or recurrent epithelial ovarian cancer who underwent cytoreductive surgery and HIPEC. We evaluated two different time periods: 2004-2013 and 2014-2022. A random-effects meta-analysis was used to produce an overall summary. Subgroup analyses were planned according to recruited period for each specific complication type. Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 4928 patients were included from 69 studies for this systematic review; 19 published from 2004-2013, and 50 published from 2014-2022. No significant differences were found between the two time periods in terms of blood transfusions (33% vs 51%; p=0.46; I2=95%) overall gastrointestinal complications (15% vs 21%; p=0.36; I2=98%), infectious diseases (16% vs 13%; p=0.62; I2=93%), overall respiratory complications (12% vs 12%; p=0.88; I2=91%), overall urinary complications (6% vs 12%; p=0.06; I2=94%), or thromboembolic events (5% vs 3%; p=0.25; I2=63%). Also, no differences were found in intensive care unit (ICU) admissions (89% vs 28%; p=0.06; I2=99%), reoperations (8% vs 7%; p=0.50; I2=37%), or deaths (3% vs 3%; p=0.77; I2=57%). CONCLUSIONS: Our review showed that overall complications have not changed over time for patients undergoing HIPEC in the setting of primary or recurrent ovarian cancer. There was no decrease in the rates of ICU admissions, reoperations, or deaths.

Diagnostic accuracy of sentinel lymph node frozen section analysis in patients with early-stage cervical cancer: A systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of intraoperative SLN frozen section analysis compared with ultrastaging in patients with early-stage cervical cancer. METHODS: A systematic literature review was conducted following the PRISMA checklist. MEDLINE (via Ovid), Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until February 2023. The inclusion criteria were patients with early-stage cervical cancer (2018 FIGO stage I-II), consisting of the histological subtype squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (≥90% of the patients in each study), who underwent SLN detection (with any tracer) and intraoperative frozen section followed by SLN ultrastaging. Randomized controlled trials, prospective and retrospective observational studies were considered. The detection rates and measures of diagnostic accuracy were pooled using a random effects univariate model. A preplanned subgroup meta-analysis was conducted, with isolated tumor cells excluded as positive lymph nodes. The review was registered in PROSPERO (CRD42023397147). RESULTS: The search identified 190 articles, with 153 studies considered potentially eligible after removing duplicates. Fourteen studies met the selection criteria, including a total of 1720 patients. Seven studies were retrospective, and the other seven were prospective. Frozen section analysis detected 159 of 292 (54.5%) patients with lymph node metastases. In 281 patients the type of volume metastasis was reported: 1 of 41 (2.4%) patients had isolated tumor cells, 21 of 78 (26.9%) patients had micrometastases, and 133 of 162 (82.1%) patients had macrometastases. The pooled sensitivity of intraoperative SLN frozen section analysis was 65% (95% CI, 51-77%) for macrometastases, micrometastases, and isolated tumor cells. When we excluded patients with isolated tumor cells, the pooled sensitivity increased to 72% (95% CI, 60-82%). CONCLUSION: SLN frozen section detects 65% of lymph node metastases compared with SLN ultrastaging and may prevent unnecessary radical surgery in some patients with early-stage cervical cancer.

MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?

OBJECTIVE: The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. METHODS: Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). RESULTS: The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. CONCLUSIONS: There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

Survival associated with extent of radical hysterectomy in early-stage cervical cancer: a subanalysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study.

BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy. RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70). CONCLUSION: For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis.