Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer.

BACKGROUND: Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking. METHODS: We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points. RESULTS: Among 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.3%). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, -1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5%; P = 0.048) and beyond 4 weeks (4.7% vs. 11.0%; P = 0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.9%; P<0.001). CONCLUSIONS: In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.).

Practice patterns, time trends and quality of care of uterine cancer in Belgium: An analysis of the EFFECT database.

OBJECTIVES: To investigate the practice patterns and quality of care for uterine cancer on a national level in Belgium, including trends in practice over the period 2012-2016. METHODS: Quality indicators were measured using the EFFectiveness of Endometrial Cancer Treatment (EFFECT) database. Multivariable logistic mixed regression was used to test for associations between the quality indicators and year of diagnosis, adjusted for potential confounders and intra-cluster correlations. RESULTS: The EFFECT database includes 4178 patients diagnosed with uterine cancer in the period 2012-2016. Minimally invasive surgery (laparoscopic or robotic-assisted) was applied in 61.6% of patients who had surgery for clinical stage I endometrial carcinoma (EC), increasing from 52.9% in 2012 to 66.4% in 2016. At least pelvic lymph node staging was performed in 69.0% of patients with clinical stage I, high-grade EC; and in 63.9% of patients with clinical stage I-II serous carcinoma, clear cell carcinoma or carcinosarcoma. The latter increased from 48.8% in 2012 to 77.2% in 2016. Adjuvant radiotherapy (external beam and/or brachytherapy) was offered to 33.5% of patients who had surgery without lymph node staging for pathological stage I EC at high-intermediate or high risk of recurrence. Adjuvant chemotherapy was administered to 64.4% of patients with pathological stage III-IVA EC. CONCLUSIONS: Study results indicate an overall good quality of care for patients with uterine cancer in Belgium. Treatment areas with potential room for improvement include the use of minimally invasive surgery, comprehensive surgical staging and adjuvant therapy, which confirms the remaining controversies in uterine cancer treatment and the need for further research.

Knowledge of cytology results affects the performance of colposcopy: a crossover study.

OBJECTIVE: To determine whether knowledge of cytology affects the colposcopist's diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2). METHOD: In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations. RESULTS: Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade. CONCLUSIONS: Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings.

The Rare of the Rarest: Placental Site Trophoblastic Tumor, Epithelioid Trophoblastic Tumor, Atypical Placental Site Nodule.

BACKGROUND: Epithelioid Trophoblastic Tumor (ETT) and Placental Site Trophoblastic Tumor (PSTT) are two of the rarest GTNs that share certain features at diagnosis and management. Atypical Placental Site Nodule (APSN) is a relatively new entity considered as a premalignant lesion. OBJECTIVES AND METHODS: The aim of this review was to summarize the main characteristics of each of these entities, their diagnostic features, and their treatment's standard of care including fertility-sparing treatments. OUTCOME: This study provides a thorough review of ETT, PSTT, and APSN. CONCLUSIONS: The reader will gain an insight view of these rare tumors arising from the intermediate trophoblast.

European multidisciplinary tumor boards support cross-border networking and increase treatment options for patients with rare gynecological tumors.

OBJECTIVE: To evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies. METHODS: The European reference network for rare gynecological tumors (EURACAN G2 domain) aims to improve the diagnosis, management, and treatment of patients with these cancers. Cross-border multidisciplinary tumor boards were initiated to facilitate intercollegiate clinical discussions across Europe and increase patients' access to specialist treatment recommendations and clinical trials. All G2 healthcare providers were invited to participate in monthly multidisciplinary meetings. Patient data were collected using a standardized form and case summaries were distributed before each meeting. After each tumor board, a meeting summary with treatment recommendations was sent to all participants and the project manager at the coordinating center. The multidisciplinary tumor board format and outcomes were regularly discussed at G2 domain meetings. Anonymized clinical data and treatment recommendations were registered in a prospective database. For this report, clinical data were collected between November 2017 and December 2020 and follow-up data retrieved until May 2021. RESULTS: During the 3-year period, 31 multidisciplinary tumor boards were held with participants from 10 countries and 20 centers. 91 individual patients were discussed between one and six times for a total of 109 case discussions. Follow-up data were retrieved from 64 patients and 80 case discussions. Adherence to treatment recommendations was 99%. Multidisciplinary tumor board recommendations resulted in 11 patients getting access to off-label treatment and one patient being enrolled in a clinical trial in another European country. 14/91 patients were recommended for surveillance only when additional treatment had been considered locally. CONCLUSION: Cross-border multidisciplinary tumor boards enable networking and clinical collaboration between healthcare professionals in different countries. Surveillance strategies, off-label drug use, and increased participation in clinical trials are possible benefits to patients with rare gynecological tumors.

Diagnostic Performance of Immunohistochemistry Compared to Molecular Techniques for Microsatellite Instability and p53 Mutation Detection in Endometrial Cancer.

Molecular algorithms may estimate the risk of recurrence and death for patients with endometrial cancer (EC) and may impact treatment decisions. To detect microsatellite instabilities (MSI) and p53 mutations, immunohistochemistry (IHC) and molecular techniques are used. To select the most appropriate method, and to have an accurate interpretation of their results, knowledge of the performance characteristics of these respective methods is essential. The objective of this study was to assess the diagnostic performance of IHC versus molecular techniques (gold standard). One hundred and thirty-two unselected EC patients were enrolled in this study. Agreement between the two diagnostic methods was assessed using Cohen's kappa coefficient. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the IHC were calculated. For MSI status, the sensitivity, specificity, PPV and NPV were 89.3%, 87.3%, 78.1% and 94.1%, respectively. Cohen's kappa coefficient was 0.74. For p53 status, the sensitivity, specificity, PPV, and NPV were 92.3%, 77.1%, 60.0% and 96.4%, respectively. Cohen's kappa coefficient was 0.59. For MSI status, IHC presented a substantial agreement with the polymerase chain reaction (PCR) approach. For the p53 status, the moderate agreement observed between IHC and next generation sequencing (NGS) methods implies that they cannot be used interchangeably.

Completeness and selection bias of a Belgian multidisciplinary, registration-based study on the EFFectiveness and quality of Endometrial Cancer Treatment (EFFECT).

BACKGROUND: With the aim of obtaining more uniformity and quality in the treatment of corpus uteri cancer in Belgium, the EFFECT project has prospectively collected detailed information on the real-world clinical care offered to 4063 Belgian women with primary corpus uteri cancer. However, as data was collected on a voluntary basis, data may be incomplete and biased. Therefore, this study aimed to assess the completeness and potential selection bias of the EFFECT database. METHODS: Five databases were deterministically coupled by use of the patient's national social security number. Participation bias was assessed by identifying characteristics associated with hospital participation in EFFECT, if any. Registration bias was assessed by identifying patient, tumor and treatment characteristics associated with patient registration by participating hospitals, if any. Uni- and multivariable logistic regression were applied. RESULTS: EFFECT covers 56% of all Belgian women diagnosed with primary corpus uteri cancer between 2012 and 2016. These women were registered by 54% of hospitals, which submitted a median of 86% of their patients. Participation of hospitals was found to be biased: low-volume and Walloon-region centers were less likely to participate. Registration of patients by participating hospitals was found to be biased: patients with a less favorable risk profile, with missing data for several clinical-pathological risk factors, that did not undergo curative surgery, and were not discussed in a multidisciplinary tumor board were less likely to be registered. CONCLUSIONS: Due to its voluntary nature, the EFFECT database suffers from a selection bias, both in terms of the hospitals choosing to participate and the patients being included by participating institutions. This study, therefore, highlights the importance of assessing the selection bias that may be present in any study that voluntarily collects clinical data not otherwise routinely collected. Nevertheless, the EFFECT database covers detailed information on the real-world clinical care offered to 56% of all Belgian women diagnosed with corpus uteri cancer between 2012 and 2016, and may therefore act as a powerful tool for measuring and improving the quality of corpus uteri cancer care in Belgium.

Importance of pathological review of gestational trophoblastic diseases: results of the Belgian Gestational Trophoblastic Diseases Registry.

OBJECTIVE: To evaluate the added value of a centralized pathology review of the diagnoses of gestational trophoblastic diseases by expert pathologists and its potential impact on clinical management in a prospective multicenter study based on the Belgian Gestational Trophoblastic Diseases Registry. METHODS: From July 2012 to December 2020, the two referral centers of the registry were solicited to advise on 1119 cases. Referral pathologists systematically reviewed all of the initial histological diagnoses. Cases initially assessed by expert pathologists were excluded. A total of 867 files were eligible for the study. Concordance between diagnoses of gestational trophoblastic diseases made by general 'non-expert' and expert pathologists was analyzed together with the potential impact of the alterations on clinical management. Expert pathologists were working in an academic setting with high exposure to placental pathology and national recognition. RESULTS: The rate of discordance between expert and non-expert pathologists for the initial diagnoses was 35%. Almost 95% of complete moles were confirmed by the expert pathologists, but only 61% for partial moles. Compared with previous studies, ancillary techniques (p57 immunohistochemistry, karyotype) were used twice as often by both groups of pathologists in this survey. The diagnosis of gestational trophoblastic neoplasia was altered in 42% of cases. When the initial diagnosis was altered, the clinical relevance of this correction was estimated as down staging, up staging, or not relevant in 65%, 33% and 2% of cases respectively. CONCLUSION: Systematic centralized pathological review of gestational trophoblastic diseases modified the diagnosis in a third of cases. The results also show that a change in diagnosis would impact clinical management in 98% of patients.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer.

OBJECTIVE: To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. METHODS: In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. RESULTS: A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. CONCLUSIONS: Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Observational BGOG Study of the Results of Robot-assisted Laparoscopy in 166 Patients with FIGO 2009 Stage IA1-IB1 Cervical Cancer.

STUDY OBJECTIVE: Two recent studies (the Laparoscopic Approach to Cervical Cancer [LACC] trial and a cohort study based on the National Cancer Database) raise the question of whether minimally invasive surgery (conventional and robot-assisted laparoscopy) is inferior to open abdominal surgery in early-stage cervical cancer. In the laparotomy group of the LACC trial, the low rates of recurrence and death are notable. The present study wants to elucidate the current situation of patients with early-stage cervical cancer treated with robot-assisted laparoscopy in hospitals of the Belgium and Luxembourg Gynaecological Oncology Group (BGOG). DESIGN: This is a prospective follow-up study. SETTING: The combined data obtained from different BGOG hospitals were analyzed regarding patients similar to those included in the LACC trial in terms of cervical cancer recurrence and survival. PATIENTS: We included patients with stage IA1, IA2, or IB1 cervical cancer with a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. INTERVENTIONS: All patients were treated with robot-assisted laparoscopy. MEASUREMENTS AND MAIN RESULTS: The outcomes were disease-free and overall survival at 3 and 5 years after surgery. A total of 270 patients were included, and 166 were found suitable for analysis. The median age was 45 years. Most patients had International Federation of Gynecology and Obstetrics stage IB1 cervical cancer (84.9%) and squamous cell carcinoma as the histologic subtype (71.7%). The median follow-up time was 44 months, with a range of between 1 and 131 months. Twenty-one recurrences and 12 deaths were noted. Of the deaths, 8 were related to cervical cancer. Disease-free survival was 86% at 3 years (95% confidence interval [CI], 78.52-90.80) and 85% at 5 years (95% CI, 77.03-89.95). Overall survival was 96% at 3 years (95% CI, 90.11-98.22) and 91% at 5 years (95% CI, 82.54 95.17). CONCLUSION: The results of this BGOG study show disease-free and overall survival rates after robot-assisted laparoscopy in early-stage cervical cancer that are at least similar to previous reported recurrence and survival data. We expect that the results of the Robot-assisted Approach to Cervical Cancer trial will elucidate the place of robot-assisted laparoscopy in early-stage cervical cancer.

Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer.

AGO-OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front-line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression-free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB-IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2 ) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2-21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with >1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83-1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh-risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75-0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports.

Tumor total lesion glycolysis and number of positive pelvic lymph nodes on pretreatment positron emission tomography/computed tomography (PET/CT) predict survival in patients with locally advanced cervical cancer.

OBJECTIVE: The aim of this study was to investigate the prognostic value of metabolic parameters obtained at pretreatment [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in patients with locally advanced cervical cancer. We hypothesize that these metabolic parameters could optimize the treatment decision and thus favor the outcome of patients suffering locally advanced cervical cancer. METHODS: Patients with locally advanced cervical cancer underwent pretreatment PET/CT. Standard uptake values (maximum, mean, peak), metabolic tumor volume, and total lesion glycolysis were measured in the tumor and in the hypermetabolic pelvic lymph nodes. The relationship between clinical, pathological, and PET/CT metabolic parameters with recurrence-free survival and overall survival was assessed by Cox regression analysis. RESULTS: 115 patients with a median age of 52 years (range 23-77) presented with locally advanced cervical cancer. After a mean follow-up of 33.0 months after initiation of therapy, 26 patients (22.6%) recurred of which 17 patients had distant metastasis; 18 (15.7%) patients died. Recurrence-free survival at 2 and 5 years was 79.2% and 72.2%, respectively. The total lesion glycolysis of the tumor and the delay between diagnosis and treatment were significantly associated with recurrence-free survival in the multivariate analysis (HR 1.00, p=0.004, and HR 2.04, p=0.02, respectively). Only the total lesion glycolysis of the tumor ≥373.54 (HR 2.49, 95% CI 1.15 to 5.38; p=0.02) remained significant after log rank testing. Overall survival at 2 and 5 years was 91.7% and 68.8%, respectively. The number of PET-positive pelvic lymph nodes was the only independent prognostic factor for overall survival in the multivariate analysis (HR 1.43, 95% CI 1.13 to 1.81; p=0.003). CONCLUSION: Tumor total lesion glycolysis and the number of positive pelvic lymph nodes on pretreatment PET/CT appear to be independent prognostic factors for recurrence and survival in patients with locally advanced cervical cancer. This may help to select patients who may benefit from therapeutic optimization and closer surveillance.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial.

OBJECTIVE: To analyze the safety and efficacy of niraparib in patients aged ≥70 years with recurrent ovarian cancer in the ENGOT-OV16/NOVA trial. METHODS: The trial enrolled 2 independent cohorts with histologically diagnosed recurrent ovarian, fallopian tube, or peritoneal cancer who responded to platinum rechallenge, on the basis of germline breast cancer susceptibility gene mutation (gBRCAmut) status. Patients were randomized 2:1 to receive niraparib (300 mg) or placebo once daily until disease progression. The primary endpoint was progression-free survival (PFS) by blinded independent central review. Adverse events (AEs) of special interest were based on the known safety profile of poly(ADP-ribose) polymerase inhibitors. RESULTS: Patients aged ≥70 years in the gBRCAmut cohort receiving niraparib (n = 14) had not yet reached a median PFS compared with a median PFS of 3.7 months for the same age group in the placebo arm (hazard ratio [HR], 0.09 [95% confidence interval (CI), 0.01 to 0.73]). Non-gBRCAmut patients aged ≥70 years receiving niraparib (n = 47) had a median PFS of 11.3 months compared with 3.8 months in the placebo arm (HR, 0.35 [95% CI, 0.18 to 0.71]). Median duration of follow-up in the niraparib arm was 17.3 months in patients ≥70 years and 17.2 months in patients <70 years. Frequency, severity of AEs, and dose reductions in the niraparib arm were similar in patients aged <70 and ≥ 70 years population. The most common grade ≥ 3 AEs in patients ≥70 years were hematologic: thrombocytopenia event (34.4%), anemia event (13.1%), and neutropenia event (16.4%). CONCLUSIONS: For patients ≥70 years of age receiving niraparib as maintenance treatment in the ENGOT-OV16/NOVA trial, PFS benefits and incidence of any grade or serious treatment-emergent AEs were comparable to results in the younger population. Use of niraparib should be considered in this population.

Human Chorionic Gonadotropin Regression Curves after Partial or Complete Molar Pregnancy in Flanders: Are They Different from Regression Curves from the Eighties?

BACKGROUND/AIMS: We updated human chorionic gonadotropin (hCG) regression curves created in the eighties after evacuation of complete and partial molar (CM and PM, respectively) pregnancies using modern hCG assays. We created similar curves for patients in need of chemotherapy (gestational trophoblastic neoplasia [GTN]). METHODS: A total of 126 patients who were diagnosed with gestational trophoblastic disease from 1990 to 2014 were included. We compared curves from 2 groups, CM and PM, with historical ones. The third group was a comparison of GTN patients receiving first-line chemotherapy and patients in need of a switch of chemotherapy. RESULTS: The regression curves were comparable to historical ones. According to the latter, mean time to normalization was 14-15 weeks after evacuation. We observed a normalization within 12 (CM) and 12.7 (PM) weeks. In addition, a remarkable but not statistically significant vertical shift (20 IU/L higher) was observed prior to day 60 compared with historical curves. The comparison in GTN patients showed a statistical significant difference, even at day 7. CONCLUSION: The presented hCG regression curves in the Flemish region were comparable with the ones of the eighties but with a vertical shift, hypothetically due to more sensitive assays. In addition, regression curves in GTN patients receiving chemotherapy can be used to evaluate response.

Brief Report on 3-Weekly Paclitaxel Carboplatin Efficacy in Locally Advanced or Metastatic Squamous Vulvar Cancer.

In this brief report, we present our experience with 3-weekly paclitaxel-carboplatin chemotherapy for patients with vulvar cancer. Two patients with locally advanced disease had an impressive response allowing standard vulvar cancer surgery. One patient with metastatic disease had local stable disease though it was progressive in the lymph nodes. The available literature is sparse and retrospective. Based on promising results, however, a prospective multicenter study is mandatory in order to obtain full data in a larger series of patients in order to learn the benefits of neoadjuvant paclitaxel-carboplatin and compare the results with chemoradiation.

Interval Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First-Line Treatment for Advanced Ovarian Carcinoma: A Feasibility Study.

OBJECTIVES: We conducted a phase 2 trial to assess the feasibility of interval cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in patients with stage III and IV pleural ovarian carcinoma in first-line treatment with no macroscopic residual disease after surgery. METHODS: Patients could be treated either with primary CS with HIPEC followed by 6 conventional cycles of chemotherapy or with 3 or 4 cycles of neoadjuvant chemotherapy before CS with HIPEC and 3 postoperative chemotherapy cycles. Hyperthermic intraperitoneal chemotherapy was performed with cisplatin (50 mg/m) for 60 minutes, only in case of complete cytoreduction. RESULTS: Nineteen patients were included in the study, and they all underwent neoadjuvant chemotherapy before CS. Sixteen patients underwent complete CS with HIPEC. There was no mortality, and morbidity of CS with HIPEC was acceptable. The HIPEC procedure did not prevent the administration of the standard first-line treatment. In the 16 patients who underwent CS with HIPEC, the outcomes were very good. CONCLUSION: Our study shows an acceptable toxicity of adding HIPEC to the standard first-line treatment in patients with stage III ovarian carcinoma treated with interval CS. Further studies are needed to confirm the role of HIPEC in the treatment of ovarian carcinoma.

Unique recurrence patterns of cervical intraepithelial neoplasia after excision of the squamocolumnar junction.

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamocolumnar junction (SCJ) and suggest that these cells may not regenerate after excision (loop electrosurgical excision procedure). Our study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (human papillomavirus, HPV) characteristics of recurrent CIN. One hundred and thirty-one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype and SCJ immunophenotype. During the follow-up period (up to 4 years), 16 (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type and were typically SCJ marker positive [SCJ(+)], suggesting nonexcised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (-). In total, 9 out of 11 SCJ (-) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This markedly lower risk of CIN 2/3 after successful SCJ excision suggests that the removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer.