Reproductive outcomes after fertility-sparing surgery for cervical cancer - results of the multicenter FERTISS study.

INTRODUCTION: Fertility-sparing treatment (FST) for patients with cervical cancer intends to achieve oncologic outcomes comparable to those after radical treatment while maximizing reproductive outcomes, including the ability to conceive and minimizing the risk of prematurity. METHODOLOGY: International multicentre retrospective FERTISS study focused on patients treated with FST analysed timing of FST relative to pregnancy, conception attempts and methods, abortion rates, prophylactic procedures reducing the risk of severe prematurity, pregnancy duration, and delivery mode. RESULTS: Of the 733 patients treated at 44 centres in 13 countries, 49.7% attempted to conceive during median follow-up of 72 months and 22.6% (166/733) patients achieved a successful pregnancy. Success rate was significantly higher after non-radical surgery (63.2%; 122/193) compared to radical trachelectomy (25.7%; 44/171, p < 0.001). Available perinatological data shows that 89.5% (111/124) of the patients became pregnant naturally. There was no significant difference in the abortion rate in the first pregnancy nor delivery success rates between non-radical and radical procedures patients. Preterm delivery (<38 weeks gestation) occurred more frequently after radical than non-radical procedures (76.5% vs. 57.7%, p = 0.15). Almost all patients (97.3%; 73/75) who underwent regular ultrasound cervicometry in pregnancy with subsequent prophylactic procedures delivered a live fetus, compared to 30.6% (15/49) women without such management, p < 0.001. CONCLUSION: Patients who underwent non-radical surgery had significantly higher pregnancy rates. Most pregnancies resulted in a viable fetus, but radical trachelectomy led to a higher rate of preterm births in the severe prematurity range. Half of the patients did not attempt pregnancy after FST.

Prediction of nonresectability using the updated Predictive Index value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study.

BACKGROUND: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of nonresectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model). OBJECTIVE: The aim was to demonstrate the noninferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI)/MRI) in predicting nonresectable tumor (defined as residual disease >1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated. STUDY DESIGN: This was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of nonresectability at ultrasound, CT, WB-DWI/MRI, and surgical exploration. Ultrasound and CT were mandatory index tests, while WB-DWI/MRI was an optional test (non-available in all centers). The predictors of nonresectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV >8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in 6 predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease >1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting nonresectability was reported. Concordance between index tests at the detection of disease at 6 predefined sites and intraoperative exploration as reference standard was also calculated using Cohen's kappa. RESULTS: The study was between 2018 and 2022 in 5 European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1 cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was>1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out, and 50/80 underwent laparoscopy only, because cytoreduction was not feasible in all of them. After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of 3 imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and nonresectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI, and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen's kappa ranging from 0.59 to 0.79) than CT and WB-DWI/MRI to assess all parameters included in the updated PIV model. CONCLUSION: Ultrasound showed noninferiority to CT and to WB-DWI/MRI in discriminating between resectable and nonresectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict nonresectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners.

Patient satisfaction with ultrasound, whole-body CT and whole-body diffusion-weighted MRI for pre-operative ovarian cancer staging: a multicenter prospective cross-sectional survey.

BACKGROUND: In addition to the diagnostic accuracy of imaging methods, patient-reported satisfaction with imaging methods is important. OBJECTIVE: To report a secondary outcome of the prospective international multicenter Imaging Study in Advanced ovArian Cancer (ISAAC Study), detailing patients' experience with abdomino-pelvic ultrasound, whole-body contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) for pre-operative ovarian cancer work-up. METHODS: In total, 144 patients with suspected ovarian cancer at four institutions in two countries (Italy, Czech Republic) underwent ultrasound, CT, and WB-DWI/MRI for pre-operative work-up between January 2020 and November 2022. After having undergone all three examinations, the patients filled in a questionnaire evaluating their overall experience and experience in five domains: preparation before the examination, duration of examination, noise during the procedure, radiation load of CT, and surrounding space. Pain perception, examination-related patient-perceived unexpected, unpleasant, or dangerous events ('adverse events'), and preferred method were also noted. RESULTS: Ultrasound was the preferred method by 49% (70/144) of responders, followed by CT (38%, 55/144), and WB-DWI/MRI (13%, 19/144) (p<0.001). The poorest experience in all domains was reported for WB-DWI/MRI, which was also associated with the largest number of patients who reported adverse events (eg, dyspnea). Patients reported higher levels of pain during the ultrasound examination than during CT and WB-DWI/MRI (p<0.001): 78% (112/144) reported no pain or mild pain, 19% (27/144) moderate pain, and 3% (5/144) reported severe pain (pain score >7 of 10) during the ultrasound examination. We did not identify any factors related to patients' preferred method. CONCLUSION: Ultrasound was the imaging method preferred by most patients despite being associated with more pain during the examination in comparison with CT and WB-DWI/MRI. TRIAL REGISTRATION NUMBER: NCT03808792.

Direct mailing of HPV self-sampling kits to women aged 50-65 non-participating in cervical screening in the Czech Republic.

BACKGROUND: A population-based cervical cancer screening programme is implemented in the Czech Republic. However, participation is insufficient among women over 50 years. This study aimed to estimate the potential improvement in participation through directly mailed HPV self-sampling kits (HPVssk) compared with standard invitation letters in women aged 50-65 non-participating in screening. METHODS: The study recruited 1564 eligible women (no cervical cancer screening in the last 3 years or more, no previous treatment associated with cervical lesions or cervical cancer). Eight hundred women were mailed with an HPVssk (HPVssk group), and 764 women were sent a standard invitation letter (control group) inviting them to a routine screening (Pap test). The primary outcome was a comparison of the overall participation rate between study groups using a binominal regression model. RESULTS: The participation rate in the HPVssk group was 13.4% [95% confidence interval (CI) 11.2-15.9%; 7.4% of women returned the HPVssk and 6.0% attended gynaecological examination] and 5.0% (95% CI 3.6-6.8%) in the control group. Using the binominal regression model, the difference between the groups was estimated as 7.6% (95% CI 5.0-10.2%; P < 0.001). In the HPVssk group, 22% of women who returned HPVssk had a positive result and 70% of them underwent a follow-up examination. CONCLUSIONS: Compared with traditional invitation letters, the direct mailing of the HPVssk achieved a significantly higher participation rate, along with a notable HPV positivity rate among HPVssk responders. This approach offers a potentially viable method for engaging women who have not yet attended a cervical screening programme.

Analysis of risk factors for recurrence in cervical cancer patients after fertility-sparing treatment: The FERTIlity Sparing Surgery retrospective multicenter study.

BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.

HPV testing as an effective triage strategy in the follow-up after fertility-sparing treatment for glandular lesions of the uterine cervix.

OBJECTIVE: The management and surveillance of glandular pre-cancerous lesions of the uterine cervix present distinct challenges compared with squamous lesions, primarily attributed to the lower effectiveness of diagnostic methods such as cytology or colposcopy. This study aimed to investigate the long-term safety of fertility-sparing treatment for adenocarcinoma in situ and microinvasive adenocarcinoma of the cervix, while identifying factors associated with recurrence, with a particular emphasis on the role of human papillomavirus (HPV) testing. METHODS: We retrospectively reviewed data from all patients with histopathologically confirmed adenocarcinoma in situ or microinvasive cervical adenocarcinoma who received treatment at a single center between 2002 and 2023. The study involved the examination of consecutive surgical specimens and the follow-up details. Factors associated with recurrence were assessed in a subgroup of patients with available long-term follow-up data (at least 6 months). RESULTS: In total, 143 patients (112 with adenocarcinoma in situ and 31 with adenocarcinoma) were included in the analysis. Among the 86 patients who underwent fertility-sparing treatment, the recurrence rate was 9% (12% for adenocarcinoma in situ and 4% for adenocarcinoma) during a median follow-up period of 56.6 months (range 7-179). No patients who were HPV negative experienced recurrence during the follow-up period. In contrast, among patients who were HPV positive, the recurrence rate was 38%. Additionally, HPV 16/18 positivity displayed a notable association with a higher risk of recurrence compared with the other high-risk genotypes, although this difference did not reach statistical significance (83% vs 10%; p=0.083, log-rank). CONCLUSION: Our retrospective study demonstrated a significant association between the risk of recurrence and HPV status during the follow-up period. Consequently, long-term follow-up utilizing HPV testing and genotyping appears to be a secure alternative to a hysterectomy.

Uterine smooth muscle tumors with uncertain malignant potential: analysis following fertility-saving procedures.

OBJECTIVE: The aim of this study was to analyze the clinical and reproductive outcomes of patients treated with myomectomy who were histologically diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP). METHODS: Patients who were diagnosed with STUMP and underwent a myomectomy at our institution between October 2003 and October 2019 were identified. Variables of interest obtained from the institution's database included patient age, relevant medical history, pre-operative appearance of the tumor on ultrasound, parameters of the surgical procedure, histopathological analysis of the tumor, post-operative clinical course, and course of follow-up, including reinterventions and fertility outcomes. RESULTS: There were a total of 46 patients that fulfilled the criteria of STUMP. The median patient age was 36 years (range, 18-48 years) and the mean follow-up was 47.6 months (range, 7-149 months). Thirty-four patients underwent primary laparoscopic procedures. Power morcellation was used for specimen extraction in 19 cases (55.9% of laparoscopic procedures). Endobag retrieval was used in nine patients and six procedures were converted to an open approach due to the suspicious peri-operative appearance of the tumor. Five patients underwent elective laparotomy due to the size and/or number of tumors; three patients had vaginal myomectomy; two patients had the tumor removed during planned cesarean section; and two underwent hysteroscopic resection.There were 13 reinterventions (five myomectomies and eight hysterectomies) with benign histology in 11 cases and STUMP histology in two cases (4.3% of all patients). We did not observe any recurrence as leiomyosarcoma or other uterine malignancy. We did not observe any deaths related to the diagnosis. Twenty-two pregnancies were recorded among 17 women, which resulted in 18 uncomplicated deliveries (17 by cesarean section and one vaginal), two missed abortions, and two pregnancy terminations. CONCLUSIONS: Our study found that uterus-saving procedures and fertility-preservation strategies in women with STUMP are feasible, safe, and seem to be associated with a low risk of malignant recurrence, even while maintaining the mini-invasive laparoscopic approach.

Fertility-sparing surgery after neo-adjuvant chemotherapy in women with cervical cancer larger than 4 cm: a systematic review.

OBJECTIVE: The objective of this systematic review was to assess the oncologic and fertility outcomes of patients with cervix-confined cancer >4 cm who underwent neo-adjuvant chemotherapy followed by fertility-sparing surgery. METHODS: This study was registered in PROSPERO (registration number CRD42021254816). PubMed/MEDLINE, ClinicalTrials, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID databases were searched from inception to July 2021. The included patients were those with cancer confined to the cervix and tumor diameter >4 cm (International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3) with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma who underwent intra-venous neo-adjuvant chemotherapy followed by successful fertility-sparing surgery. RESULTS: The initial search identified 2990 articles. A total of 40 patients from 11 studies had attempted fertility preservation surgery (conization, simple or radical trachelectomy) and in 26 patients (65%) it was successful. All patients received platinum-based chemotherapy. A complete pathological response occurred in 56% of patients and two patients (7.7%) had a recurrence. The 4.5-year disease-free survival was 92.3% and the 4.5-year overall survival rate was 100%. Of six patients who tried to conceive, four (67%) achieved at least one pregnancy and three of the five pregnancies (60%) were pre-term deliveries (all after radical trachelectomy). All patients with recurrence received cisplatin and ifosfamide instead of cisplatin and paclitaxel, underwent non-radical surgery, and had residual disease in the final specimen. CONCLUSIONS: Evidence for fertility-sparing surgery after neo-adjuvant chemotherapy in patients with cervical cancer and tumors >4 cm is limited, and this approach should be considered as an experimental intervention. As the use of non-radical surgery could be a risk factor, if neo-adjuvant chemotherapy is used, patients should undergo fertility-sparing radical surgery.

CERVANTES: an international randomized trial of radical surgery followed by adjuvant (chemo) radiation versus no further treatment in patients with early-stage, intermediate-risk cervical cancer (CEEGOG-CX-05; ENGOT-CX16).

BACKGROUND: The role of adjuvant treatment in the intermediate-risk group of patients with early-stage cervical cancer is controversial and is supported by a single randomized Gynecologic Oncology Group (GOG) 92 study performed more than 20 years ago. Recent retrospective studies have shown excellent local control in this group of patients after radical surgery with no additional adjuvant treatment. PRIMARY OBJECTIVE: To evaluate if adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with intermediate-risk cervical cancer. STUDY HYPOTHESIS: Radical surgery alone is non-inferior to the combined treatment of radical surgery followed by adjuvant (chemo)radiation in disease-free survival in patients with intermediate-risk cervical cancer. TRIAL DESIGN: This is a phase III, international, multicenter, randomized, non-inferiority trial in which patients with intermediate-risk cervical cancer will be randomized 1:1 into arm A, with no additional treatment after radical surgery, and arm B, receiving adjuvant external beam radiotherapy±brachytherapy ± concomitant chemotherapy. Patient data will be collected over 3 years post-randomization of the last enrolled patient for primary endpoint analysis or for 6 years for the overall survival analysis. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients with intermediate-risk early-stage cervical cancer (IB1-IIA), defined as lymph node-negative patients with a combination of negative prognostic factors (tumor size >4 cm; tumor size >2 cm and lymphovascular space invasion; deep stromal invasion >2/3; or tumor-free distance <3 mm) with squamous cell carcinoma or human papillomavirus (HPV)-related adenocarcinoma, are eligible for the trial. PRIMARY ENDPOINT: Disease-free survival defined as time from randomization to recurrence diagnosis. SAMPLE SIZE: 514 patients from up to 90 sites will be randomized. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: It is estimated that the accrual will be completed by 2027 (with 3 additional years of follow-up) and primary endpoint results will be published by 2031. Estimated trial completion is by 2034. TRIAL REGISTRATION: NCT04989647.

Current knowledge on fertility-sparing treatment of cervical cancer patients.

INTRODUCTION: Cervical cancer directly affects the reproductive function of women of childbearing age. Up to one-third of the disease is dia-gnosed in women younger than 45 years of age, who may still have open reproductive plans. Therefore, in recent years, there has been increasing interest in performing fertility-sparing treatment (FST), which aims to preserve fertility while achieving the same oncologic safety as radical surgical treatment. OBJECTIVE: To summarize the current knowledge on FST in women with early stages of cervical cancer. METHODS: Review of published literature on the topic using medical databases. RESULTS: FST is reserved for patients with HPV-associated cervical cancer up to stage IB with negative nodes. Conservative procedures (conization and simple vaginal trachelectomy) and radical trachelectomy are available. Conservative procedures for tumors 2cm have comparable oncological outcomes as radical treatment with a significantly lower rate of perinatological complications. On average, 55% of patients become pregnant after treatment and of these, on average 70% give birth to a live newborn. Approximately 38% of deliveries are preterm, most often after radical trachelectomy. The most common postoperative complication with direct impact on fertility is cervical stenosis. CONCLUSION: In a selected group of patients with tumors up to 2cm, FST is a safe procedure with good perinatological outcomes. However, it remains unclear whether it is safe to offer this treatment to patients with larger tumors. The use of neoadjuvant chemotherapy followed by conservative surgery is a promising approach but requires further validation in clinical trials.

Current data on the efficacy of prophylactic HPV vaccination in the primary prevention of cervical lesions.

OBJECTIVE: A review of current knowledge on the efficacy of HPV (human papillomavirus) HPV vaccination against pre-cancers and cervical cancer. METHODS AND RESULTS: HPV infection is probably the most common sexually transmitted disease and the cause of approximately 5% of all human cancers. Currently, three prophylactic vaccines against HPV infection are on the market: bivalent Cervarix, quadrivalent Gardasil (formerly Silgard) and nonavalent Gardasil9. The Czech Republic is one of the countries with a national vaccination program where HPV vaccination is covered by health insurance for girls and boys aged 13-14 years. Extensive scientific data on the efficacy of the vaccines clearly demonstrate significant efficacy against the development of cervical pre-cancers for all three vaccines. According to a high-certainty evidence of the Cochrane database, the efficacy of HPV vaccines against cervical intraepithelial neoplasia grade 2 or 3 associated with HPV 16, 18 compared with placebo in girls and women aged 15-26 is 99%. There is also moderate-certainty evidence that HPV vaccines reduce the risk of adenocarcinoma in situ for approximately 90% for the same population. Initial data also demonstrate a direct impact on reducing the incidence of invasive cervical cancer in vaccinated individuals. In addition, quadrivalent and nonavalent vaccines are highly effective in preventing genital warts. CONCLUSION: All three available prophylactic vaccines show high efficacy in preventing the development of cervical lesions. Efficacy is highest against lesions caused by vaccine genotypes and the highest efficacy is achieved in the HPV naive population.

Tumour-free distance: a novel prognostic marker in patients with early-stage cervical cancer treated by primary surgery.

BACKGROUND: Models predicting recurrence risk (RR) of cervical cancer are used to tailor adjuvant treatment after radical surgery. The goal of our study was to compare available prognostic factors and to develop a prognostic model that would be easy to standardise and use in routine clinical practice. METHODS: All consecutive patients with early-stage cervical cancer treated by primary surgery in a single referral centre (01/2007-12/2016) were eligible if assessed by standardised protocols for pre-operative imaging and pathology. Fifteen prognostic markers were evaluated in 379 patients, out of which 320 lymph node (LN)-negative. RESULTS: The best predictive model for the whole cohort entailed a combination of tumour-free distance (TFD) ≤ 3.5 mm and LN positivity, which separated two subgroups with a substantially distinct RR 36% and 6.5%, respectively. In LN-negative patients, a combination of TFD ≤ 3.5 mm and adenosquamous tumour type separated a group of nine patients with RR 33% from the rest of the group with 6% RR. CONCLUSIONS: A newly identified prognostic marker, TFD, surpassed all traditional tumour-related markers in the RR assessment. Predictive models combining TFD, which can be easily accessed on pre-operative imaging, with LN status or tumour type can be used in daily practice and can help to identify patients with the highest RR.

Impact of sentinel lymph node frozen section evaluation to avoid combined treatment in early-stage cervical cancer.

BACKGROUND: The need for radical surgery followed by adjuvant chemoradiation may be reduced by abandoning radical surgery in patients in whom lymph node involvement is detected intra-operatively. OBJECTIVES: To analyze, in a retrospective cohort study, the efficacy of the algorithm using intra-operative pathological assessment of sentinel lymph nodes. METHODS: A retrospective single-institution study was carried out, which analyzed data from all consecutive patients with cervical cancer who were referred for primary surgical treatment between May 2005 and December 2015. Inclusion criteria were as follows: (1) TNM stage T1a1 with lymphovascular space invasion, T1a2, T1b, T2a, and selected T2b with incipient parametrial invasion; (2) adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma; (3) no evidence of enlarged suspicious nodes or distant metastases on pre-operative imaging; (4) primary surgery with curative intent; (5) successful detection of sentinel lymph node, at least, unilaterally. All patients had at least one sentinel lymph node detected and submitted for frozen section evaluation. When sentinel lymph node involvement was detected intra-operatively, the cervical procedure was abandoned and the patient was referred for definitive chemoradiation. Radical surgery was completed in patients with intra-operative negative sentinel lymph nodes. The reliability of intra-operative sentinel lymph node assessment was evaluated by calculating the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: The study included a total of 309 patients. Sentinel lymph nodes were detected bilaterally in 86% of the patients. Lymph node positivity was detected intra-operatively in 18 (6%) patients in whom the cervical procedure was abandoned. Adjuvant radiotherapy after completed radical surgery was given to 29 (9%) patients, including 20 patients with macrometastases (8) or micrometastases (12) reported from the final histology, eight patients with positive parametria (all ≤3 mm), and one patient with a positive vaginal resection margin. The sensitivity, specificity, positive predictive value, and negative predictive value for the intra-operative detection of lymph node positivity (macrometastases or micrometastases) was 47% (95% CI 31% to 64%), 100%, 100%, and 93% (95% CI 90% to 96%), respectively. A total of 18 (6%) patients were spared combined treatment owing to the intra-operative sentinel lymph node triage; 29 patients (9%) received combined treatment with both radical surgery and adjuvant radiotherapy CONCLUSIONS: Of 47 patients with high-risk prognostic risk factors (lymph node, parametria, or surgical margin involvement), combined treatment was successfully avoided in 18 (38%). Despite an effort to triage the patients intra-operatively, 9% received a combination of cervical procedure and adjuvant chemoradiation, mostly owing to the low sensitivity of the frozen section in the detection of micrometastases and macrometastases.

Management of pregnancy after fertility-sparing surgery for cervical cancer.

Cervical cancer is increasingly diagnosed in women who have not yet completed their reproductive plans. For women with early-stage disease (FIGO stage IA1-IB1), fertility-sparing procedures, such as conization, trachelectomy or radical trachelectomy, represent the treatments of choice. However, women who undergo repeated conization or trachelectomy represent a challenge for obstetricians because they are at increased risk of infertility, mid-trimester miscarriage, preterm premature rupture of membranes and preterm delivery. So far, the evidence-based guidance on the management of these pregnancies is limited. This article reviews the literature discussing pregnancy management in women after fertility-sparing surgery for early cervical cancer. Although the evidence is limited, certain measures are desirable, including screening and treatment of asymptomatic bacteriuria, screening for cervical incompetence and progressive cervical shortening by transvaginal ultrasonography, and fetal fibronectin testing. Vaginal progesterone supplementation should be primary prevention for all women after trachelectomy. Women with a history of preterm delivery or late miscarriage may benefit from cervical cerclage. Elective delivery by cesarean section in the early-term period is desirable.

The role of a pathologist in surgical staging for carcinoma of the cervix uteri.

The incidence of cervical cancer is high in the Czech Republic. Altogether 822 new cases were found in this country during 2016 which means the incidence 15,3 new diseases / 100,000 women. FIGO (Fédération Internationale de Gynécologie et d´Obstétrique) staging of carcinoma for the cervix was changed as follows. Lateral extension measurement is removed in the stage IA, the only criterion is the measured deepest invasion.

One-step nucleic acid amplification vs ultrastaging in the detection of sentinel lymph node metastasis in endometrial cancer patients.

BACKGROUND AND OBJECTIVES: Utilisation of the one-step nucleic acid amplification (OSNA) molecular biology method for the detection of the metastatic involvement of sentinel lymph nodes (SLNs) in endometrial cancer (EC) patients. A comparison with histopathological ultrastaging and a description of the clinical consequences. METHODS: Surgically treated EC patients underwent detection of SLNs. Nodes greater than 5 mm were cut into sections 2-mm thick parallel to the short axis of the node. Odd sections were examined according to the OSNA method, while even ones according to an appropriate ultrastaging protocol. Nodes less than or equal to 5 mm were cut into halves along the longitudinal axis with one half examined according to the OSNA method and the other half by ultrastaging. RESULTS: Fifty-eight patients were included and 135 SLNs were acquired. Both ultrastaging and OSNA agreed on 116 results. According to the OSNA method, 20.69% more patients were classified into International Federation of Gynecology and Obstetrics (FIGO) stage III. When comparing the results of the OSNA method to the conclusions of ultrastaging as a reference method, sensitivity of 90.9%, specificity of 85.5% and concordance of 85.9% were attained. CONCLUSIONS: The results of the OSNA method showed a higher frequency of detection of micrometastases and included 20.69% more patients into FIGO stage III.

Oncological outcome of surgical management in patients with recurrent uterine cancer-a multicenter retrospective cohort study-CEEGOG EX01 Trial.

OBJECTIVES: To assess the survival of patients who have received an operation for recurrent cervical and endometrial cancer and to determine prognostic variables for improved oncologic outcome. METHODS: A retrospective multicenter analysis of the medical records of 518 patients with cervical (N = 288) or endometrial cancer (N = 230) who underwent surgery for disease recurrence and who had completed at least 1 year of follow-up. RESULTS: The median survival reached 57 months for patients with cervical cancer and 113 months for patients with endometrial cancer after surgical treatment of recurrence (p = 0.036). Histological sub-type had a significant impact on overall survival, with the best outcome in endometrial endometrioid cancer (121 months), followed by cervical squamous cell carcinoma, cervical adenocarcinoma, or other types of endometrial cancer (81 vs 35 vs 35 months; p <0.001). The site of recurrence did not significantly influence survival in cervical or in endometrial cancer. Cancer stage at first diagnosis, tumor grade, lymph node status at recurrence, progression-free interval after first diagnosis, and free resection margins were associated with improved overall survival on univariate analysis. On multivariate analysis, the stage at first diagnosis and resection margins were significant independent predictive parameters of an improved oncologic outcome. CONCLUSION: Long-term survival can be achieved via secondary cytoreductive surgery in selected patients with recurrent cervical and endometrial cancer. An excellent outcome is possible even if the recurrence site is located in the lymph nodes. The possibility of achieving complete resection should be the main criterion for patient selection.

Surgical treatment of "intermediate risk" lymph node negative cervical cancer patients without adjuvant radiotherapy-A retrospective cohort study and review of the literature.

OBJECTIVES: The role of adjuvant radiotherapy for lymph node-negative stage IB patients with tumor-related negative prognostic factors is not uniformly accepted. It is advocated based on the GOG 92 trial, which was initiated in 1989. The aim of the current study is to report the oncological outcome of "intermediate risk" patients treated by tailored surgery without adjuvant radiotherapy. Data from two institutions that refer these patients for adjuvant radiotherapy served as a control group. METHODS: Included were patients with stage IB cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, who had negative pelvic lymph nodes but a combination of negative prognostic factors adopted from the GOG 92 trial. Data were obtained from prospectively collected databases of three institutions. Radical surgery was a single-treatment modality in one of them and in the remaining two institutes it was followed by adjuvant chemoradiation. RESULTS: In 127 patients who received only radical surgery, with a median follow-up of 6.1 years, the local recurrence rate was 1.6% (2 cases), and total recurrence was 6.3% (8 cases). Disease-specific survival at 5 years was 95.7% (91.9%; 99.4%) and 91% (83.7%; 98.3%) at 10 years. The only significant factor for disease-specific survival was tumor size ≥4 cm (P = 0.032). The recurrence rate, local control or overall survival did not differ from the control group. Adjuvant radiotherapy was not a significant prognostic factor within the whole cohort. CONCLUSIONS: An excellent oncological outcome, especially local control, can be achieved by both radical surgery or combined treatment in stage IB lymph node-negative cervical cancer patients with negative prognostic factors. The substantially better outcome than in the GOG 92 trial can be attributed to more accurate pre-operative and pathological staging and an improvement in surgical techniques.

[Anogenital HPV Infection as the Potential Risk Factor for Oropharyngeal Carcinoma]. / Anogenitální HPV infekce jako potenciální rizikový faktor orofaryngeálního karcinomu.

BACKGROUND: Human papillomavirus (HPV) can cause cervical, other genital, anal, head, and neck cancers. The incidence of oropharyngeal squamous cell carcinoma (OSCC), the head and neck cancer most commonly caused by HPV infection, is increasing. The prevalence of oral HPV infections is considerably lower than that of genital HPV infections; however, infection of both sites is strongly associated with sexual behavior. Although the natural histories of cervical and oral HPV infections do not markedly differ, the virus seems to rarely infect oral and genital sites simultaneously. On the other hand, the standardized incidence ratio of OSCC is higher in cervical cancer patients than in other populations. Furthermore, women with OSCC have a significantly increased risk of developing HPV-related genital cancers. Administration of the HPV vaccine to both genders will undoubtedly dramatically change the epidemiology of HPV-related cancers. AIM: This work provides an overview of the literature and estimates the risk of OSCC in women with anogenital HPV infections. CONCLUSION: The biological relationship between different HPV-infected sites might be complex; however, the increased prevalence of HPV in oral samples of women positive for anogenital HPV indicates that such infections are unlikely to be independent of one another. Sexual activity likely affects the risk of concurrent anogenital and oral coinfections. However, it is also possible that one infection site provides a reservoir that can increase the risk of autoinoculation at anatomically distant locations or that coinfections develop as a result of other factors, such as immunodeficiency. Nevertheless, women with HPV-associated malignancy undoubtedly have a higher risk of developing OSCC.Key words: human papillomavirus - HPV - genital HPV infection - oral HPV infection - oropharyngeal squamous cell carcinoma - standardized incidence ratio - head and neck cancer This article was supported by by the project UNCE 204065 of Charles University. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 26. 8. 2017Accepted: 4. 1. 2018.

Sensitivity of Follow-Up Methods in Patients After Fertility-Sparing Surgery for Cervical Cancers.

OBJECTIVE: The aim of our study was to compare the sensitivity of various methods and their combinations in the follow-up of patients with cervical cancer after fertility-sparing surgery (FSS). METHODS: Included were women with cervical cancer in stages IA2 to IB2 who underwent FSS, which includes pelvic lymphadenectomy, sentinel lymph node biopsy, abdominal radical trachelectomy, vaginal trachelectomy, or needle conization. Follow-up visits were scheduled at 3-month intervals and included symptom-oriented discussion, gynecological and physical examination, colposcopy, Papanicolaou test, human papillomavirus (HPV) DNA test, and ultrasound examination. All cases with a recurrent disease were thoroughly analyzed, and the results of individual examinations were compared. RESULTS: In total, 43 women (IA2, 8; IB1, 33; IB2, 2) were enrolled. The mean patient age was 31 years; most patients were nulliparous (68.4%, 26/38) with squamous cell cancers (26/38). Abdominal radical trachelectomy was performed in 10 women, simple vaginal trachelectomy was performed in 11 women, and conization was performed in 22 women, according to the tumor characteristics and topography. The median duration of the follow-up reached 37 months. Invasive cancer and high- and low-grade squamous intraepithelial lesions were detected in 8, 1, and 1 patients, respectively. All except 1 event were central, detected within the first year after FSS. Only 2 cases were symptomatic. Colposcopy detected 7 of 10 recurrences; 5 of them were HPV positive, and, in 2 cases, a Papanicolaou test revealed abnormalities. Papanicolaou tests were false positive in 27.7%, especially after trachelectomies. CONCLUSIONS: Most patients in whom cancer recurred after FSS reveal central or pelvic lesions, which can be successfully treated with salvage surgery or radiotherapy. The early detection of recurrence is an essential condition for a favorable oncological outcome. Colposcopy alone and in combination with HPV positivity showed the highest sensitivity for the detection of recurrent diseases, whereas other methods had limited reliability.