Anxiety and depression among women with newly diagnosed vulvar cancer - A nationwide longitudinal study.

INTRODUCTION: Our objective was to investigate the trajectories of anxiety, depression, emotional and social functioning in women with newly diagnosed vulvar cancer from the time of diagnosis to 12 months after treatment. A further aim was to identify risk factors for high levels of anxiety. MATERIAL AND METHODS: PROVE (PROspective Vulvar Cancer Evaluation) is a nationwide longitudinal cohort study investigating quality of life in women with newly diagnosed vulvar cancer by the following validated patient-reported outcome measures at diagnosis, and 3 and 12 months after treatment: The Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Vulvar module VU34. Mean scores, changes over time and associations were analyzed by generalized estimated equations and log-linear regression models, adjusted for possible confounders. RESULTS: Between 2019 and 2021, 105 (69%) women completed the questionnaires at all three time points. At diagnosis, 42% of the women reported elevated anxiety levels, decreasing significantly to 30% during the first 12 months. Insomnia, persisting vulvar symptoms and high information needs were significantly associated with a high level of anxiety (relative risk [RR] 2.1, 95% CI 1.2-3.7 for insomnia; RR 2.8, 95% CI 1.7-4.6 for vulvar symptoms, RR 2.7, 95% CI 1.5-4.9 for information needs). We found a trend towards a higher level of anxiety in younger women (<65 years: RR 1.5, 95% CI 1.0-2.5). Participants reported a low and stable prevalence of depression (14%) and high social functioning throughout the study period. CONCLUSIONS: Women with newly diagnosed vulvar cancer report a high level of anxiety at diagnosis. Despite a significant improvement, anxiety remains widely prevalent during the first year of follow-up. Targeting insomnia, vulvar symptoms and unmet needs may decrease anxiety during surveillance.

Impact of radiotherapy on bone health in women with rectal cancer - A prospective cohort study.

INTRODUCTION: Pelvic radiotherapy (RT) increases the risk of pelvic insufficiency fractures. The aim was to investigate if RT is associated with changes in serum bone biomarkers in women with rectal cancer, and to examine the incidence of radiation-induced bone injuries and the association with bone biomarkers. MATERIAL AND METHODS: Women diagnosed with rectal cancer stage I-III, planned for abdominal surgery ± preoperative (chemo) RT, were prospectively included and followed one year. Serum bone biomarkers comprised sclerostin (regulatory of bone formation), CTX (resorption), BALP and PINP (formation). A subgroup was investigated with annual pelvic magnetic resonance imaging (MRI). The association between RT and bone biomarkers was explored in regression models. RESULTS: Of 134 included women, 104 had surgery with preoperative RT. The formation markers BALP and PINP increased from baseline to one year in the RT-exposed group (p < 0.001, longitudinal comparison). In the adjusted regression analysis, the mean increase in PINP was higher in the RT-exposed than the unexposed group (17.6 (3.6-31.5) µg/L, p = 0.013). Sclerostin and CTX did not change within groups nor differed between groups. Radiation-induced injuries were detected in 16 (42%) of 38 women with available MRI. At one year, BALP was higher among women with than without bone injuries (p = 0.018, cross-sectional comparison). CONCLUSIONS: Preoperative RT was associated with an increase in the formation marker PINP, which could represent bone recovery following RT-induced injuries, commonly observed in participants evaluated with MRI. These findings should be further explored in larger prospective studies on bone health in rectal cancer patients.

Long-term incidence of endometrial cancer after endometrial resection and ablation: A population based Swedish gynecologic cancer group (SweGCG) study.

INTRODUCTION: Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long-term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately. MATERIAL AND METHODS: The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997-2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow-up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow-up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis. RESULTS: In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow-up time of 7.1 years (interquartile range 3.1-13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population-based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03-0.53) after EA and 1.27 (95% CI 0.86-1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively. CONCLUSIONS: There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate.

The wait time to primary surgery in endometrial cancer - impact on survival and predictive factors: a population-based SweGCG study.

BACKGROUND: Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. MATERIAL AND METHODS: In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). RESULTS: Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. CONCLUSIONS: Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.HighlightsSurgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival.A prolonged wait time to surgery did not worsen prognosis.Delay in time to surgery was associated with sociodemographic factors.

Impact of Androgens on Sexual Function in Women With Rectal Cancer - A Prospective Cohort Study.

BACKGROUND: Women treated for rectal cancer are at risk of sexual dysfunction and impaired ovarian androgen production. AIM: To investigate a possible association between serum levels of endogenous androgens and sexual function in women with rectal cancer. METHODS: Women diagnosed with stage I-III rectal cancer were consecutively included and prospectively followed with the Female Sexual Function Index (FSFI) questionnaire from baseline to 2 years postoperatively and blood samples for hormone analyses, baseline to 1 year. Androgens were measured with liquid chromatography-mass spectrometry and electrochemiluminescence. The associations between the 4 measured androgens (testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulphate) and sexual function were assessed with generalized least squares random effects regression analysis in sexually active women. OUTCOMES: The primary outcome measure was the mean change observed in the FSFI total score when the serum androgen levels changed with one unit. Secondary outcomes were the corresponding mean changes in the FSFI domain scores: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain/discomfort. RESULTS: In the 99 participants, the median FSFI total score decreased from 21.9 (range 2.0 - 36.0) to 16.4 (3.5 - 34.5) and 11.5 (2.0 to 34.8) at 1 and 2-years follow-up. After adjustment for age, partner, psychological well-being, preoperative (chemo)radiotherapy, and surgery, total testosterone and androstenedione were significantly associated with FSFI total score (ß-coefficients 3.45 (95% CI 0.92 - 5.97) and 1.39 (0.46 - 2.33) respectively). Testosterone was significantly associated with the FSFI-domains lubrication and orgasm, free testosterone with lubrication, androstenedione with all domains except desire and satisfaction, and dehydroepiandrosterone sulphate with none of the domains. STRENGTHS AND LIMITATIONS: This is the first study investigating whether androgen levels are of importance for the impaired sexual function seen in women following rectal cancer treatment. The prospective design allows for repeated measures and the use of the FSFI for comparisons across studies. No laboratory data were collected at the 2-year follow-up, and the missing data could have further clarified the studied associations. CONCLUSION AND CLINICAL IMPLICATION: Testosterone and androstenedione were associated with sexual function in female rectal cancer patients. The results are of interest for future intervention studies and contribute to the understanding of sexual problems, which is an essential component of the rehabilitation process in pelvic cancer survivors. Svanström Röjvall A, Buchli C, Flöter Rådestad A, et al. Impact of Androgens on Sexual Function in Women With Rectal Cancer - A Prospective Cohort Study. J Sex Med 2021;18:1374-1382.

Survival in endometrial cancer in relation to minimally invasive surgery or open surgery - a Swedish Gynecologic Cancer Group (SweGCG) study.

BACKGROUND: The aim of this study was to analyze overall survival in endometrial cancer patients' FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). METHODS: A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. RESULTS: In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18-1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95-1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. CONCLUSION: The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

Patterns of recurrence and survival in vulvar cancer: A nationwide population-based study.

OBJECTIVE: To examine the patterns of recurrence and how these patterns are associated with survival in vulvar squamous cell carcinoma. We also explored the survival impact of surgical groin staging (SGS). METHODS: Nationwide population-based study including women diagnosed with vulvar squamous cell carcinoma between 2012 and 2015 and registered in the Swedish Quality Registry for Gynecologic Cancer. Cumulative incidence rates (CIR), recurrence-free (RFS) and overall survival (OS) were calculated by Kaplan Meier estimates. The impact of SGS on RFS and OS was analyzed by proportional hazards models. RESULTS: 489 eligible women were included. Median follow-up time was 64 months. The overall recurrence rate was 22.3%. Site of recurrence: local in 61.0%, groin in 30.0%, distant in 9.0%. The CIR for local recurrences increased with time (5.9% at 2-years, 14.7% at 5-years) while the rate of groin and distant recurrences was nearly steady (5.5% to 6.3% and 1.5% to 1.7%, respectively). Median 2-year and 4-year OS post-recurrence was 57.8% and 37.4% for local, 17.2%, 10.3% for groin and 0% for distant recurrences, respectively. SGS was omitted in 23.7% of surgically treated women with FIGO stages IB-II and significantly associated with worse RFS (Hazard ratio, HR, 1.9; 95%CI, 1.0-3.5; p = 0.04) and OS (HR 2.0; 95%CI, 1.1-3.8; p = 0.04) after adjustment for age, FIGO stage, tumor size, resection margins and performance status. CONCLUSION: The cumulative incidence of isolated vulvar recurrence was low but for those affected the prognosis was poor. Surgical groin staging is a crucial part of primary treatment and should not be omitted.

Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer-A Swedish Gynecologic Cancer Group (SweGCG) study.

INTRODUCTION: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice. MATERIAL AND METHODS: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I-III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard. RESULTS: In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively. CONCLUSIONS: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI.

Reproductive and obstetrical outcomes with the overall survival of fertile-age women treated with fertility-sparing surgery for borderline ovarian tumors in Sweden: a prospective nationwide population-based study.

OBJECTIVE: To assess the efficacy of fertility-sparing surgery (FSS) in terms of reproductive outcomes by following FSS for borderline ovarian tumors (BOTs) and comparing the safety of FSS versus radical surgery (RS). DESIGN: Nationwide cohort study based on prospectively recorded data. SETTING: Sweden. PATIENT (S): All women of reproductive age (18-40 years) treated in Sweden for stage I BOT with the use of FSS or RS from 2008 to 2015, identified in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). INTERVENTIONS (S): FSS or RS. MAIN OUTCOME MEASURE (S): Reproductive outcomes: natural conception, use of assisted reproductive technology (ART), live birth and obstetrical outcomes. Safety outcome: overall survival (OS) rates, comparing women undergoing FSS versus RS. The FSS cohort was linked to the Swedish Medical Birth Register to identify all women who had given birth after FSS and to obtain detailed obstetrical data. For information on ART treatment, the National Quality Registry for Assisted Reproduction was consulted. OS rate comparisons were conducted by means of Kaplan-Meier estimates. RESULT (S): Of the 277 women with BOTs, 213 (77%) underwent FSS, 183 (86%) unilateral salpingo-oophorectomy, and 30 (14%) cystectomy. Following FSS, 50 women gave birth to 62 healthy children, 8% of which were preterm. Only 20 (9%) of the women underwent ART treatment. OS was similar in women treated with FSS and RS. CONCLUSION (S): Natural fertility was maintained after FSS; only 9% required ART treatment. FSS was also deemed to be equivalent to RS regarding survival outcome.

A Swedish Nationwide prospective study of oncological and reproductive outcome following fertility-sparing surgery for treatment of early stage epithelial ovarian cancer in young women.

BACKGROUND: Epithelial ovarian cancer (EOC) is rare in women of reproductive age and fertility-sparing surgery (FSS) may be applied in early stages. The purpose of this study was to investigate the safety and efficacy of FSS for treatment of EOC. METHODS: The Swedish nationwide population-based Quality Register for Gynecological Cancer was used to identify all women 18-40 years of age diagnosed with stage I EOC between 2008 and 2015. Detailed data on surgery, staging, histopathology, and follow-up were extracted and reviewed. Cross-linking of individuals to population-based registries allowed retrieval of data on obstetrical and reproductive outcomes after FSS. Disease-free survival (DFS) and overall survival (OS) rates were compared (Kaplan-Meier method) between women who underwent FSS vs. radical surgery (RS). RESULTS: In total 83 women were identified; 36 who had FSS performed and 47 RS. The 5-year OS rate was 92% and no statistical differences between DFS or OS were found between women treated by FSS or RS. The recurrence rate after RS was 13% compared to 6% after FSS. Recurrences were more frequently found in women with stage IC tumor or with histologic subtypes with more aggressive behavior. In the FSS cohort, nine women gave birth to 12 healthy children, all delivered at fullterm. Only one women had received assisted reproductive technology treatment. CONCLUSION: In this nationwide population-based cohort study natural fertility was maintained after FSS. Specific histologic subtypes showed greater prognostic impact on the oncological outcome than the use of FSS. Recurrences occurred after FSS, but none in the uterus, which questions the need of hysterectomy in young women with EOC. TRIAL REGISTRATION: This article reports the results of a healthcare intervention using the data prospectively registered in the Swedish population-based registries including the Quality Register for Gynecological Cancer, the National Death Register, the Swedish Medical Birth Register, and the National Quality Register for Assisted Reproduction.

Primary treatment and relative survival by stage and age in vulvar squamous cell carcinoma: A population-based SweGCG study.

OBJECTIVE: Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group. METHODS: A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort. RESULTS: Median follow-up time was 41 months. The study population included 657 women; 33% were ≥ 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women ≥80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women ≥80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III. CONCLUSIONS: In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden adhered to guidelines. Areas of improvement include treatment for stage II and for the very old.

Primary treatment patterns and survival of cervical cancer in Sweden: A population-based Swedish Gynecologic Cancer Group Study.

OBJECTIVE: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. METHODS: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. RESULTS: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p < 0.001). In stage IIA1 74% had CT-RT, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy (BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p < 0.001). Stages III-IVA; <40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p < 0.001). RS stage IVB 7%. CONCLUSION: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy.

Fertility-sparing surgery for treatment of non-epithelial ovarian cancer: Oncological and reproductive outcomes in a prospective nationwide population-based cohort study.

OBJECTIVE: To compare the oncologic outcome of women who underwent fertility-sparing surgery (FSS) vs. radical surgery (RS) for treatment of NEOC in a prospective, nationwide, population-based study and report on the reproductive outcomes in women after FSS. METHODS: Using the Swedish Quality Register for Gynecological Cancer, we identified all women ages 18-40 treated with either FSS or RS for stage I NEOC between 2008 and 2015. Progression-free survival (PFS) and overall survival (OS) rates were compared using the Kaplan-Meier method. Data on use of assisted reproductive technology (ART) treatments and obstetrical outcomes after FSS were extracted from the National Quality Register for Assisted Reproduction (Q-IVF) and the Swedish Medical Birth Register. RESULTS: During the study period, 73 women ages 18-40 received a stage I NEOC diagnosis. The majority, 78% (n = 57), underwent FSS. The 5-year OS rate, regardless of surgical approach, was 98%. There were no statistical differences between OS and PFS rates in women treated with FSS, compared to RS. Recurrences were more common after RS than FSS: 12.5% (2/16) vs. 3.5% (2/57), respectively. Following FSS, 11 women gave birth to 13 healthy children (all conceived naturally). Additionally, 12% of the women in the cohort developed infertility and received ART treatment (n = 7). CONCLUSION: FSS is not associated with worse oncologic outcomes than RS in young women with early stage NEOC. The prognosis was excellent in both groups, with an OS of 98%. Natural fertility was maintained in women treated with FSS, only 12% required ART treatment.

Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer - a Swedish Gynecologic Cancer Group (SweGCG) study.

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma.Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated.Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69-8.07, p < .001) followed by deep myometrial invasion (RR = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05-5.98) was associated with a worsened overall survival.Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.

Mifepristone mediates anti-proliferative effect on ovarian mesenchymal stem/stromal cells from female BRCA1-/2- carriers.

INTRODUCTION: Women with hereditary mutation in breast cancer-associated genes (BRCA1-/2- ) have a higher lifetime risk of developing ovarian cancer. Here, we aimed to investigate the effect of mifepristone, a selective progesterone receptor modulator of ovarian mesenchymal stem/stromal cells (MSC) from BRCA1-/2- carriers. MATERIAL AND METHODS: Ovarian BRCA1-/2- MSC were positively selected using the markers CD90, CD73 and CD105 from nine healthy women. The effect of dose response and combination treatment with mifepristone and analogs of progesterone- or glucocorticoid-receptors were investigated on BRCA1-/2- MSC in vitro using a panel of markers for proliferation (ki67, BrdU, CDK2, p21CIP ), apoptosis (BAX, BCL2, CASPASE3), tumor suppression (TP53, PTEN) and cell survival (PI3KCA, MAPK3, mTOR). RESULTS: The dose response with mifepristone treatment suggested an optimal effect with 10 µm mifepristone, exhibiting >90% viability and significantly reducing growth signaling markers (TP53 and MAPK3). Furthermore, combined treatment with progesterone plus mifepristone (PG+MIFE) gave an enhanced anti-proliferative effect in comparison with hydrocortisone plus mifepristone (HC+MIFE) by significantly reducing markers of proliferation (BrdU+ and Ki67 expression) and tumor suppressors (PTEN, TP53), and increasing the percentage of pro-apoptotic cells. Consequently, accumulation of p21CIP together with reduced levels of CDK2 confirms growth inhibition by reversibly arresting cell-cycle progression at the G1-S phase, not by inducing apoptosis. CONCLUSIONS: Our study showed an anti-proliferative effect on ovarian BRCA1-/2- MSC on in vitro combined treatment with mifepristone and progesterone. These findings suggest that mifepristone or other selective progesterone receptor modulators could be developed as a preventive treatment and postpone early use of prophylactic salpingo-oophorectomy as well as reduce the risk of ovarian cancer.

Introduction of robot-assisted radical hysterectomy for early stage cervical cancer: impact on complications, costs and oncologic outcome.

INTRODUCTION: The objective was to assess the impact of robot-assisted radical hysterectomy (RRH) on surgical and oncologic outcome and costs compared with open radical hysterectomy (ORH) at a tertiary referral center in Sweden. MATERIAL AND METHODS: In this retrospective analysis all patients treated with radical hysterectomy and pelvic lymphadenectomy for early stage uterine cervical cancer during 2006-2015 were included (n = 304). The patients were divided into two groups, ORH (n = 155) and RRH (n = 149). Patient characteristics, FIGO stage, histology, adjuvant therapy, operation time, length of stay (LOS), lymph node yield, recurrence rate and survival were retrieved from medical records. Complications were graded according to the Clavien-Dindo classification. In addition, costs related to the surgical treatments were calculated. RESULTS: Blood loss, LOS and intraoperative complications were significantly lower as well as lymph node yield after RRH. No differences in postoperative complications or costs were observed between the two groups. Recurrence of disease was detected in 13.4 and 10.3% after RRH and ORH, respectively. Regression analysis demonstrated that histology, tumor size, positive lymph nodes and type of operation (RRH) were significantly associated with recurrence. CONCLUSION: The introduction of RRH was accompanied by similar postoperative complication rates and costs but lower LOS compared with ORH. An initial learning curve may account for the higher recurrence rate observed after RRH. These data reinforce the need for structured training and monitoring of outcomes when novel treatment modalities are introduced.

Serous tubal intraepithelial carcinoma, chronic fallopian tube injury, and serous carcinoma development.

Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p < 0.001). No differences in tubal injury or inflammation were seen when comparing the sporadic serous cancer group and the control group or within the hereditary group. STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.

Serum Androgen Levels and Sexual Function Before and One Year After Treatment of Uterine Cervical Cancer: A Pilot Study.

INTRODUCTION: Radiotherapy or radical hysterectomy with salpingo-oophorectomy (SOE) as treatment for uterine cervical cancer causes estrogen deprivation in premenopausal women. The effects on androgen production have rarely been examined but could be relevant for survivors of cervical cancer because insufficiency has been associated with low sexual function. AIM: To investigate the effects of pelvic radiotherapy, hysterectomy with SOE, or surgery without SOE on androgen levels and to explore potential associations with sexual function. METHODS: Patients with cervical cancer (N = 60) were prospectively examined through blood sampling and questionnaires before and 1 year after treatments. MAIN OUTCOME MEASURES: Serum testosterone (measured by liquid chromatography and tandem mass spectrometry), sex hormone-binding globulin, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone, luteinizing hormone, and estradiol levels and Female Sexual Function Index scores. RESULTS: In women treated with radiotherapy (n = 38), median total and free testosterone levels were significantly decreased at 1-year follow-up compared with baseline in premenopausal women (n = 16; total testosterone -29%, P = .01; free testosterone -22%, P = .007) and postmenopausal women (n = 22; total testosterone -25%, P = .03; free testosterone -29%, P = .03). Androstenedione was decreased in premenopausal women only and dehydroepiandrosterone sulfate was decreased in postmenopausal women only after radiotherapy. In women treated with hysterectomy and SOE (n = 10), testosterone levels were lower but not significantly lower, and there was no change in those having surgery without SOE (n = 12). Female Sexual Function Index scores lower than 26.5 in sexually active women were reported by 80% 1 year after radiotherapy, by 44% after hysterectomy with SOE, and by 40% after surgery without SOE, with no significant differences compared with baseline values. No direct correlation between androgen levels and Female Sexual Function Index scores were found at 1-year follow-up. CONCLUSION: Total and free testosterone levels decreased slightly but significantly after pelvic radiotherapy in pre- and postmenopausal women. The clinical importance of this decrease is unclear, but androgen levels were not directly related to sexual function in this pilot setting.

[Hormone therapy in menopause can increase the risk of ovarian cancer]. / Hormonbehandling i klimakteriet kan ge risk för ovarialcancer - Nya studieresultat ger dock inte anledning att ändra rekommendationerna.

Risk of ovarian cancer should be added to the list of adverse effects of hormone replacement therapy (HRT). However there is no need for change in clinical recommendations. The recommendation today is to prescribe the lowest dose and shortest time of HRT for menopausal symptom relief. Our clinical approach should be to include among other risk factors the risk of one extra case of ovarian cancer/1000 users for 5 years of HRT versus reduced quality of life without HRT for each woman.

Anti-Müllerian hormone in premenopausal women following treatment of uterine cervical cancer.

In this longitudinal study we prospectively enrolled 32 premenopausal women (ages 23-44 years) with stage I-III uterine cervical cancer undergoing surgery and/or chemoradiation. Serum levels of anti-Müllerian hormone, follicle-stimulating hormone and estradiol were examined at baseline and 1 year after treatment. As expected, serum anti-Müllerian hormone was undetectable after salpingo-oophorectomy or chemoradiation. After radical hysterectomy and pelvic lymphadenectomy with ovarian preservation serum anti-Müllerian hormone declined from a mean value of 2.0 ± 1.4 µg/L to 1.1 ± 0.8 µg/L (p = 0.01), representing a 45% reduction, whereas there was no significant change in serum levels of follicle-stimulating hormone and estradiol. This implies that ovarian function may be affected not only by castrating treatment but also by radical hysterectomy with ovarian preservation. The risk of premature menopause and the potential need of hormone replacement therapy among these women may be overlooked since they no longer menstruate.