Treatment of FIGO 2018 stage IIIC cervical cancer with different local tumor factors.

BACKGROUND: To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). METHODS: Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan-Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. RESULTS: We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150-2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255-2.182, P < 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.226 and P = 0.921) or DFS (P = 0.343 and P = 0.535) than R-CT. In the T2a group, NACT was correlated with a decrease in OS (HR = 1.454, 95% CI: 1.057-2.000, P = 0.021) and DFS (HR = 1.529, 95% CI: 1.185-1.974, P = 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.736 and P = 0.267) or DFS (P = 0.714 and P = 0.087) than R-CT. In the T2b group, NACT was correlated with a decrease in DFS (HR = 1.847, 95% CI: 1.347-2.532, P < 0.001) than R-CT nevertheless was not correlated with OS (P = 0.146); ARH was not correlated with OS (P = 0.056) and DFS (P = 0.676). In the T3 group, the OS rates of ARH (n = 10), NACT (n = 18), and R-CT (n = 1053) were 67.5%, 53.1%, and 64.7% (P = 0.941), and the DFS rates were 68.6%, 45.5%, and 61.1%, respectively (P = 0.761). CONCLUSION: R-CT oncological outcomes were not entirely superior to those of NACT or ARH under different local tumor factors with stage IIIC. NACT is not suitable for stage T1, T2a, and T2b. Nevertheless ARH is potentially applicable to stage T1, T2a, T2b and T3. The results of stage T3 require confirmation through further research due to disparity in case numbers in each subgroup.

Comparison of survival outcomes with or without Para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer in China from 2004 to 2016.

BACKGROUND: Current opinions on whether surgical patients with cervical cancer should undergo para-aortic lymphadenectomy at the same time are inconsistent. The present study examined differences in survival outcomes with or without para-aortic lymphadenectomy in surgical patients with stage IB1-IIA2 cervical cancer. METHODS: We retrospectively compared the survival outcomes of 8802 stage IB1-IIA2 cervical cancer patients (FIGO 2009) who underwent abdominal radical hysterectomy + pelvic lymphadenectomy (n = 8445) or abdominal radical hysterectomy + pelvic lymphadenectomy + para-aortic lymphadenectomy (n = 357) from 37 hospitals in mainland China. RESULTS: Among the 8802 patients with stage IB1-IIA2 cervical cancer, 1618 (18.38%) patients had postoperative pelvic lymph node metastases, and 37 (10.36%) patients had para-aortic lymph node metastasis. When pelvic lymph nodes had metastases, the para-aortic lymph node simultaneous metastasis rate was 30.00% (36/120). The risk of isolated para-aortic lymph node metastasis was 0.42% (1/237). There were no significant differences in the survival outcomes between the para-aortic lymph node unresected and resected groups. No differences in the survival outcomes were found before or after matching between the two groups regardless of pelvic lymph node negativity/positivity. CONCLUSION: Para-aortic lymphadenectomy did not improve 5-year survival outcomes in surgical patients with stage IB1-IIA2 cervical cancer. Therefore, when pelvic lymph node metastasis is negative, the risk of isolated para-aortic lymph node metastasis is very low, and para-aortic lymphadenectomy is not recommended. When pelvic lymph node metastasis is positive, para-aortic lymphadenectomy should be carefully selected because of the high risk of this procedure.

Computed tomography-based radiomic model at node level for the prediction of normal-sized lymph node metastasis in cervical cancer.

PURPOSE: Radiomic models have been demonstrated to have acceptable discrimination capability for detecting lymph node metastasis (LNM). We aimed to develop a computed tomography-based radiomic model and validate its usefulness in the prediction of normal-sized LNM at node level in cervical cancer. METHODS: A total of 273 LNs of 219 patients from 10 centers were evaluated in this study. We randomly divided the LNs from the 2 centers with the largest number of LNs into the training and internal validation cohorts, and the rest as the external validation cohort. Radiomic features were extracted from the arterial and venous phase images. We trained an artificial neural network (ANN) to develop two single-phase models. A radiomic model reflecting the features of two-phase images was also built for directly predicting LNM in cervical cancer. Moreover, four state-of-the-art methods were used for comparison. The performance of all models was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Among the models we built, the models combining the features of two phases surpassed the single-phase models, and the models generated by ANN had better performance than the others. We found that the radiomic model achieved the highest AUCs of 0.912 and 0.859 in the training and internal validation cohorts, respectively. In the external validation cohort, the AUC of the radiomic model was 0.800. CONCLUSION: We constructed a radiomic model that exhibited great ability in the prediction of LNM. The application of the model could optimize clinical staging and decision-making.

Comparative study on the oncological prognosis of laparoscopy and laparotomy for stage IIA1 cervical squamous cell carcinoma.

OBJECTIVE: To compare the 5-year overall survival (OS) and disease-free survival (DFS) rate of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IIA1 cervical squamous cell carcinoma. METHODS: Based on a large database containing information on the clinical diagnosis and treatment of cervical cancer in China, the oncological outcomes of the two surgical approaches for stage IIA1 cervical squamous cell carcinoma were compared after 1:2 propensity score matching (PSM). RESULTS: After 1:2 propensity score matching (PSM), 510 patients were included in the LRH group, and 999 patients were included in the ARH group. LRH showed a similar 5-year OS but a lower DFS rate (81.3% vs. 87.4%, P = 0.018) than ARH. In the multivariate analysis, LRH was identified as an independent risk factor for worse 5-year DFS (HR = 1.569, 95% CI: 1.131-2.176, P = 0.007). Among patients with a tumour size <2 cm, the LRH and ARH groups showed similar OS and DFS rates after 1:2 PSM, and multivariate analysis showed that the surgical approach was not an independent risk factor affecting the OS or DFS rate. Among patients with a tumour size ≥2 cm and <4 cm, there was no difference in OS between the LRH and ARH groups after matching, but the DFS in the LRH group was significantly lower than that in the ARH group (81.1% vs 86.2%, P = 0.034). In the multivariate analysis, the laparoscopic approach was not associated with OS but was independently associated with worse DFS (HR = 1.546, 95% CI: 1.094-2.185, P = 0.014). CONCLUSIONS: LRH was associated with poorer 5-year DFS than ARH in patients with stage IIA1 cervical squamous cell carcinoma. However, LRH showed 5-year OS and DFS rates similar to those of ARH among patients with a tumour size <2 cm. For patients with a tumour size ≥2 cm and <4 cm, LRH showed a lower DFS rate than ARH.

Influence of uterine corpus invasion on prognosis in stage IA2-IIB cervical cancer: A multicenter retrospective cohort study.

OBJECTIVE: To determine the associations between the presence and depth of uterine corpus invasion and survival in patients with cervical cancer. METHODS: Clinical data of patients with stage IA2-IIB cervical cancer who underwent radical hysterectomy between 2004 and 2016 were retrospectively reviewed. Uterine corpus invasion was identified from a review of uterine pathology. Independent prognostic factors for 5-year disease-free survival (DFS) and overall survival (OS) were identified using multivariate forward stepwise Cox proportional hazards regression models. RESULTS: A total of 1414 patients with stage IA2-IIB cervical cancer from 11 medical institutions in China were included. Retrospective review of the original pathology reports revealed a missed diagnosis of uterine corpus invasion in 38 (13.4%) patients and a misdiagnosis in 20 (1.8%) patients. Therefore, 284 patients with cervical cancer and uterine corpus invasion (90 [31.7%] patients had endometrial invasion, 105 [37.0%] patients had myometrial invasion <50%, and 89 [31.3%] patients had myometrial invasion ≥50%), and 1130 patients with cervical cancer without uterine corpus invasion were included in the analysis. The 5-year DFS and OS were significantly shorter for patients with uterine corpus invasion compared to patients with no uterine corpus invasion. Myometrial invasion ≥50% was an independent prognostic factor associated with decreased 5-year DFS (aHR, 2.307, 95% CI, 1.588-3.351) and 5-year OS (aHR, 2.736, 95% CI, 1.813-4.130), while myometrial invasion <50% or endometrial invasion had no effect on patient outcomes. CONCLUSIONS: Diagnosis of uterine corpus invasion is frequently missed. Myometrial invasion ≥50% within the uterine corpus was an independent factor associated with worse prognosis in patients with cervical cancer, while myometrial invasion <50% or endometrial invasion had no effect on outcomes.

Prediction of Response to Preoperative Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer Using Multicenter CT-Based Radiomic Analysis.

Objective: To investigate whether pre-treatment CT-derived radiomic features could be applied for prediction of clinical response to neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer (LACC). Patients and Methods: Two hundred and seventy-seven LACC patients treated with NACT followed by surgery/radiotherapy were included in this multi-institution retrospective study. One thousand and ninety-four radiomic features were extracted from venous contrast enhanced and non-enhanced CT imaging for each patient. Five combined methods of feature selection were used to reduce dimension of features. Radiomics signature was constructed by Random Forest (RF) method in a primary cohort of 221 patients. A combined model incorporating radiomics signature with clinical factors was developed using multivariable logistic regression. Prediction performance was then tested in a validation cohort of 56 patients. Results: Radiomics signature containing pre- and post-contrast imaging features can adequately distinguish chemotherapeutic responders from non-responders in both primary and validation cohorts [AUCs: 0.773 (95% CI, 0.701-0.845) and 0.816 (95% CI, 0.690-0.942), respectively] and remain relatively stable across centers. The combined model has a better predictive performance with an AUC of 0.803 (95% CI, 0.734-0.872) in the primary set and an AUC of 0.821 (95% CI, 0.697-0.946) in the validation set, compared to radiomics signature alone. Both models showed good discrimination, calibration. Conclusion: Newly developed radiomic model provided an easy-to-use predictor of chemotherapeutic response with improved predictive ability, which might facilitate optimal treatment strategies tailored for individual LACC patients.

Noninvasive CT radiomic model for preoperative prediction of lymph node metastasis in early cervical carcinoma.

OBJECTIVE: To build and validate a CT radiomic model for pre-operatively predicting lymph node metastasis in early cervical carcinoma. METHODS AND MATERIALS: A data set of 150 patients with Stage IB1 to IIA2 cervical carcinoma was retrospectively collected from the Nanfang hospital and separated into a training cohort (n = 104) and test cohort (n = 46). A total of 348 radiomic features were extracted from the delay phase of CT images. Mann-Whitney U test, recursive feature elimination, and backward elimination were used to select key radiomic features. Ridge logistics regression was used to build a radiomic model for prediction of lymph node metastasis (LNM) status by combining radiomic and clinical features. The area under the receiver operating characteristic curve (AUC) and κ test were applied to verify the model. RESULTS: Two radiomic features from delay phase CT images and one clinical feature were associated with LNM status: log-sigma-2-0 mm-3D_glcm_Idn (p = 0.01937), wavelet-HL_firstorder_Median (p = 0.03592), and Stage IB (p = 0.03608). Radiomic model was built consisting of the three features, and the AUCs were 0.80 (95% confidence interval: 0.70 ~ 0.90) and 0.75 (95% confidence intervalI: 0.53 ~ 0.93) in training and test cohorts, respectively. The κ coefficient was 0.84, showing excellent consistency. CONCLUSION: A non-invasive radiomic model, combining two radiomic features and a International Federation of Gynecology and Obstetrics stage, was built for prediction of LNM status in early cervical carcinoma. This model could serve as a pre-operative tool. ADVANCES IN KNOWLEDGE: A noninvasive CT radiomic model, combining two radiomic features and the International Federation of Gynecology and Obstetrics stage, was built for prediction of LNM status in early cervical carcinoma.

Neurovascular and lymphatic vessels distribution in uterine ligaments based on a 3D reconstruction of histological study: to determine the optimal plane for nerve-sparing radical hysterectomy.

OBJECTIVE: To present the distribution of neurovascular and lymphatic vessels in uterine ligaments using 3D models based on the pathological staining of serial 2D sections of postoperative specimens. METHODS: Serial transverse sections of fresh uterine ligaments from a patient with stage IB1 cervical squamous cell carcinoma were studied using the computer-assisted anatomic dissection (CAAD) technique. The sections were stained with hematoxylin and eosin, Weigert elastic fibers, D2-40 and immunostainings (sheep anti-tyrosine hydroxylase and rabbit anti-vasoactive intestinal peptide). The sections were then digitalized, registered and reconstructed three-dimensionally. Then, the 3D models were analyzed and measured. RESULTS: The 3D models of the neurovascular and lymphatic vessels in uterine ligaments were created, depicting their precise location and distribution. The vessels were primarily located in the upper part of the ligaments model, while the pelvic autonomic nerves were primarily in the lower part; the lymphatic vessels were scattered in the uterine ligaments, without obvious regularity. CONCLUSION: CAAD is an effective anatomical method to study the precise distribution of neurovascular and lymphatic vessels in uterine ligaments. It can present detailed anatomical information about female pelvic autonomic innervation and the spatial relationship between nerves and vessels and may provide a better understanding of nerve-sparing radical hysterectomy.