Fertility-Sparing Surgery versus Radical Hysterectomy in Early Cervical Cancer: A Propensity Score Matching Analysis and Noninferiority Study

Early cervical cancer; Fertility-sparing surgery; Radical hysterectomyCáncer de cuello uterino temprano; Cirugía conservadora de la fertilidad; Histerectomía radicalCàncer de coll uterí precoç; Cirurgia conservadora de la fertilitat; Histerectomia radicalObjective: Fertility-sparing surgery (FSS) is the treatment of choice for patients with early cervical cancer (ECC) and fertility desire, but survival rates compared to radical hysterectomy (RH) have been scarcely reported. The aim of this study was to analyse the oncological outcomes of FSS compared to a balanced group of standard RH. Methods: A retrospective multicentre study of ECC patients who underwent FSS or RH was carried out in 12 tertiary hospitals in Spain between January 2005 and January 2019. The experimental group included patients who underwent a simple and radical trachelectomy, and the control group included patients who underwent RH. Optimal 1:1 propensity score (PS) matching analysis was performed to balance the series. Results: The study included 222 patients with ECC; 111 (50%) were treated with FSS, and 111 (50%) were treated with RH. After PS matching, a total of 38 patients in the FSS group and 38 patients in the RH group were analysed. In both groups, the overall survival (HR 2.5; CI 0.89, 7.41) and recurrence rates (28.9% in the FSS group vs. 13.2% in RH group) were similar. The rate of disease-free survival at 5 years was 68.99% in the FSS group and 88.01% in the RH group (difference of −19.02 percentage points; 95% CI −32.08 to −5.96 for noninferiority). In the univariate analysis, only tumour size reached statistical significance. Conclusion: FSS offers excellent disease-free and overall survival in women with ECC with fertility desire and is not inferior compared to RH.This work received financial support from the Medtronic University Chair for Training and Surgical Research, University Jaume I (UJI), Castellon, Spain

Fertility-Sparing Surgery versus Radical Hysterectomy in Early Cervical Cancer : A Propensity Score Matching Analysis and Noninferiority Study

Fertility-sparing surgery (FSS) is the treatment of choice for patients with early cervical cancer (ECC) and fertility desire, but survival rates compared to radical hysterectomy (RH) have been scarcely reported. The aim of this study was to analyse the oncological outcomes of FSS compared to a balanced group of standard RH. A retrospective multicentre study of ECC patients who underwent FSS or RH was carried out in 12 tertiary hospitals in Spain between January 2005 and January 2019. The experimental group included patients who underwent a simple and radical trachelectomy, and the control group included patients who underwent RH. Optimal 1:1 propensity score (PS) matching analysis was performed to balance the series. The study included 222 patients with ECC; 111 (50%) were treated with FSS, and 111 (50%) were treated with RH. After PS matching, a total of 38 patients in the FSS group and 38 patients in the RH group were analysed. In both groups, the overall survival (HR 2.5; CI 0.89, 7.41) and recurrence rates (28.9% in the FSS group vs. 13.2% in RH group) were similar. The rate of disease-free survival at 5 years was 68.99% in the FSS group and 88.01% in the RH group (difference of −19.02 percentage points; 95% CI −32.08 to −5.96 for noninferiority). In the univariate analysis, only tumour size reached statistical significance. FSS offers excellent disease-free and overall survival in women with ECC with fertility desire and is not inferior compared to RH

Fertility-Sparing Surgery versus Radical Hysterectomy in Early Cervical Cancer: A Propensity Score Matching Analysis and Noninferiority Study

Objective: Fertility-sparing surgery (FSS) is the treatment of choice for patients with early cervical cancer (ECC) and fertility desire, but survival rates compared to radical hysterectomy (RH) have been scarcely reported. The aim of this study was to analyse the oncological outcomes of FSS compared to a balanced group of standard RH. Methods: A retrospective multicentre study of ECC patients who underwent FSS or RH was carried out in 12 tertiary hospitals in Spain between January 2005 and January 2019. The experimental group included patients who underwent a simple and radical trachelectomy, and the control group included patients who underwent RH. Optimal 1:1 propensity score (PS) matching analysis was performed to balance the series. Results: The study included 222 patients with ECC; 111 (50%) were treated with FSS, and 111 (50%) were treated with RH. After PS matching, a total of 38 patients in the FSS group and 38 patients in the RH group were analysed. In both groups, the overall survival (HR 2.5; CI 0.89, 7.41) and recurrence rates (28.9% in the FSS group vs. 13.2% in RH group) were similar. The rate of disease-free survival at 5 years was 68.99% in the FSS group and 88.01% in the RH group (difference of −19.02 percentage points; 95% CI −32.08 to −5.96 for noninferiority). In the univariate analysis, only tumour size reached statistical significance. Conclusion: FSS offers excellent disease-free and overall survival in women with ECC with fertility desire and is not inferior compared to RH

Intraoperative electron radiation therapy after salvage surgery in gynecological cancers and retroperitoneal sarcomas: outcomes and adverse effects

Background: Salvage surgery is considered an option for isolated recurrences of retroperitoneal and pelvic tumors, in patients who have undergone previous radiotherapy. In order to increase local control intra operative electron radiation therapy (IOERT) can be used in these patients to administer additional radiation dose. We evaluated the outcomes and adverse effects in patients with retroperitoneal sarcoma and gynecologic tumors after salvage surgery and IOERT. Materials and methods: Twenty patients were retrospectively analyzed. Twenty-three IOERT treatments were performed after surgery. Six (30%) were sarcoma and 14 (70%) were gynecological carcinoma. Administered dose depended on previous dose received with external beam radiotherapy (EBRT) and proximity to critical structures. The toxicities were scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of the patients was 51 years (range 34–70). After a median follow-up of 32 months (range 1–68), in the sarcoma group the local control rate was 66.6%; while in the gynecological group the local control rate was 64.3%. In relation to late toxicity, one patient had a Grade 2 vesicovaginal fistula, and one patient presented Grade 4 enterocolitis and enteric intestinal fistula. Conclusions: IOERT could have a role in the treatment of retroperitoneal sarcomas in primary tumors after EBRT, as it may suggest a benefit in local control or recurrences after surgical resection in those at high risk of microscopic residual disease. The addition of IOERT to salvage resection for isolated recurrence of gynecologic cancers suggest favorable local control in cases with concern for residual microscopic disease

"Primary Squamous Cell Carcinoma of the Vagina: HPV Detection, p16INK4A Overexpression and Clinicopathological Correlations"

International audienceAim: To determine the role of HPV in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinico-pathological significance. Methods: All cases of SCCVa diagnosed over a 15 year period from two hospitals in Barcelona, Spain (n=32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed less than 5 years before were excluded. HPV was detected and typed by PCR using the SPF10 primers. Immunohistochemistry for p16 and p53 was performed. Results: HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV-positive tumours were frequently associated with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% vs. 0%; p=0.01). HPV-positive tumours were more frequently of non-keratinizing, basaloid or warty type than HPV-negative neoplasms (84% vs. 14.3%; p<0.001), and almost constantly showed diffuse positive staining for p16INK4a (96%, vs. 14.3%; p<0.001). The sensitivity and specificity of p16 to identify HPV-positive tumours were 96% and 85.7% respectively. Conclusions: A high number of SCCVs are related to HPV infection and may be identified by immunostaining for p16. HPV-positive tumours tend to affect women with history of cervical neoplasm

Malacoplakia of the Uterine Cervix: A Case Report

Malacoplakia is an uncommon chronic granulomatous inflammation that rarely affects the female genital tract. A case of a 78-year-old woman with malacoplakia involving the uterine cervix and the vagina is described. The patient complained of vaginal bleeding. Clinically, a 13-mm mass was detected in the cervix, which was confirmed by ultrasound scan and magnetic resonance imaging. Histological examination showed a dense histiocytic infiltrate with abundant Michaelis–Gutmann bodies involving the uterine cervix and the upper vagina. The presence of Escherichia coli was confirmed in the lesion by immunohistochemistry and polymerase chain reaction. Only 12 cases of cervical malacoplakia have been reported to date. This condition should be included in the differential diagnosis of cervical tumors

Malacoplakia of the Uterine Cervix: A Case Report

Malacoplakia is an uncommon chronic granulomatous inflammation that rarely affects the female genital tract. A case of a 78-year-old woman with malacoplakia involving the uterine cervix and the vagina is described. The patient complained of vaginal bleeding. Clinically, a 13-mm mass was detected in the cervix, which was confirmed by ultrasound scan and magnetic resonance imaging. Histological examination showed a dense histiocytic infiltrate with abundant Michaelis-Gutmann bodies involving the uterine cervix and the upper vagina. The presence of Escherichia coli was confirmed in the lesion by immunohistochemistry and polymerase chain reaction. Only 12 cases of cervical malacoplakia have been reported to date. This condition should be included in the differential diagnosis of cervical tumors

Late G2 vagina toxicity in post-operative endometrial carcinoma is associated with a 68 Gy dose equivalent to 2 Gy per fraction(α/β=3Gy) at 2 cm3 of vagina

[Purpose] To evaluate if the dose equivalent to 2 Gy per fraction (EQD2)(α/β=3Gy) at 0.1 cm3, 1 cm3, and 2 cm3 of vagina in vaginal-cuff-brachytherapy (VBT) (high-dose-rate [HDR] 192Ir-source) ± external-beam-irradiation (EBRT) is associated with toxicity in post-operative endometrial carcinoma (P-EC). [Material and methods] From June 2014 till November 2015, 67 consecutive P-EC patients underwent VBT ± EBRT; 44 patients received EBRT (median, 45 Gy; range, 44-50.4) + VBT (7 Gy), and 23 exclusive-VBT (6 Gy x 3 fractions). The upper 2.5 cm of vagina was delineated on computed tomography (CT). The active-length source was 2.5 cm, and the brachytherapy dose was prescribed at 5 mm from the applicator. D90, V100, and EQD2(α/β=3Gy) at 0.1 cm3, 1 cm3, and 2 cm3 of the most exposed part of the vagina were calculated. Vaginal toxicity assessment was completed with a LENT-SOMA-objective-criteria. Statistics were done with the use of χ2 and Student’s-t test. [Results] The mean follow-up was 23.2 months (7.6-46.8). Median D90 was 7.8 Gy(α/β=3Gy). Late toxicity: 8 G1 and 9 G2. Median EQD2(α/β=3Gy) in vagina was 88.6 Gy (62.8-177.6) for 0.1 cm3, 72.4 Gy (57.1-130.4) for 1 cm3, and 69 Gy (53-113.4) for 2 cm3. Exclusive VBT vs. EBRT+VBT showed no differences in vaginal toxicity. There was no relationship between EQD2(α/β=3Gy) at 0.1 cm3 and 1 cm3 of vagina with G1-G2 toxicity (p = 0.62 and p = 0.58, respectively). G2 toxicity was related to EQD2(α/β=3Gy) at 2 cm3 (p = 0.03). EQD2(α/β=3Gy) > 68 Gy caused G2 late toxicity in 20.5% patients. All patients presenting G2 toxicity received > 68 Gy EQD2(α/β=3Gy). [Conclusions] More than 68 Gy EQD2(α/β=3Gy) at 2 cm3 was related to G2 toxicity in P-EC-VBT. Further studies including larger number of patients are needed to confirm these results. Patients receiving these doses should be informed of the risk of toxicity, with individualized treatment planning and follow-up to reduce G2 toxicity.This study was supported by a grant from the Spanish Association Against Cancer (AECC) Foundation.Peer reviewe

The Value of Endocervical Curettage in Addition to Biopsies in Women Referred to Colposcopy

Objective Performing endocervical curettage (ECC) at colposcopy may increase the yield of cervical intraepithelial neoplasia grade 2 (CIN2) or worse (CIN2+) compared to biopsies alone. The additional benefit of ECC in detecting CIN2+ was studied in women with lesion-targeted biopsies (low-grade or worse impression) and women with biopsies of normal-appearing cervix (less than low-grade impression). Methods In this subanalysis of a multicenter study, 126 women referred to colposcopy who had an ECC were included. Multiple directed biopsies were taken from lesions, and a nontargeted biopsy was added if fewer than 4 biopsies were collected. Risk strata of CIN2+ were evaluated based on cytology and colposcopic appearance to identify women for whom ECC would be most valuable. Results The CIN2+ yield of ECC in addition to biopsies was 15 (11.9%) of 126. In women with lesion-targeted biopsies and ECC, the CIN2+ yield of targeted biopsies was 34 (51.5%) of 66, the yield of additional nontargeted biopsies was 1 (1.5%) of 66, and the additional CIN2+ yield of ECC was 5 (7.6%) of 66. The yield in women with nontargeted biopsies only and ECC was 5 (8.3%) 60, and the additional yield for ECC was 10 (16.7%) of 60. Endocervical curettage did not find disease in women with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion. Conclusions In women with less than low-grade impression and especially those with unsatisfactory colposcopy, the yield of CIN2+ was higher for ECC compared to nontargeted biopsies. The highest yield of CIN2+ from ECC was observed in women with high-grade squamous intraepithelial lesion and less than low-grade impression, suggesting that disease is higher up in the endocervix in this group