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.).

Efficacy of a nurse-led sexual rehabilitation intervention for women with gynaecological cancers receiving radiotherapy: results of a randomised trial.

BACKGROUND: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers. METHODS: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time. RESULTS: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly. DISCUSSION: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment. CLINICAL TRIAL REGISTRATION: NCT03611517.

Prognostic value of molecular classification in stage IV endometrial cancer.

OBJECTIVES: Multiple studies have proven the prognostic value of molecular classification for stage I-III endometrial cancer patients. However, studies on the relevance of molecular classification for stage IV endometrial cancer patients are lacking. Hypothetically, poor prognostic molecular subtypes are more common in higher stages of endometrial cancer. Considering the poor prognosis of stage IV endometrial cancer patients, it is questionable whether molecular classification has additional prognostic value. Therefore, we determined which molecular subclasses are found in stage IV endometrial cancer and if there is a correlation with progression-free and overall survival. METHODS: A retrospective multicenter cohort study was conducted using data from five Dutch hospitals. Patients with stage IV endometrial cancer at diagnosis who were treated with primary cytoreductive surgery or cytoreductive surgery after induction chemotherapy between January 2000 and December 2018 were included. Exclusion criteria were age <18 years or recurrent disease. The molecular classification was performed centrally on all tumor samples according to the World Health Organization 2020 classification (including POLE and estrogen receptor status). The Kaplan-Meier method was used to calculate progression free and overall survival in the molecular subclasses, for the different histological subtypes and for estrogen receptor positive versus estrogen receptor negative tumors. Groups were compared using the log-rank test. RESULTS: 164 stage IV endometrial cancer patients were molecularly classified. Median age of the patients was 67 years (range 33-86). Most patients presented with a non-endometrioid histological subtype (58%). Intra-abdominal complete cytoreductive surgery was achieved in 60.4% of the patients. 101 tumors (61.6%) were classified as p53 abnormal, 35 (21.3%) as no specific molecular profile, 21 (12.8%) as mismatch repair deficient, and 6 (3%) as POLE mutated. Molecular classification had no significant impact on progression free (p=0.056) or overall survival (p=0.12) after cytoreductive surgery. Overall survival was affected by histologic subtype (p<0.0001) and estrogen receptor status (p=0.013). CONCLUSION: The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I-III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions.

Near-infrared fluorescence imaging compared to standard sentinel lymph node detection with blue dye in patients with vulvar cancer - a randomized controlled trial.

OBJECTIVE: The aim of this study was to assess the superiority of ICG-99mTc-nanocolloid for the intraoperative visual detection of sentinel lymph nodes (SLNs) in vulvar squamous cell carcinoma (VSCC) patients compared to standard SLN detection using 99mTc-nanocolloid with blue dye. METHODS: In this multicenter, randomized controlled trial, VSCC patients underwent either the standard SLN procedure or with the hybrid tracer ICG-99mTc-nanocolloid. The primary endpoint was the percentage of fluorescent SLNs compared to blue SLNs. Secondary endpoints were successful SLN procedures, surgical outcomes and postoperative complications. RESULTS: Forty-eight patients were randomized to the standard (n = 24) or fluorescence imaging group (n = 24) using ICG-99mTc-nanocolloid. The percentage of blue SLNs was 65.3% compared to 92.5% fluorescent SLNs (p < 0.001). A successful SLN procedure was obtained in 92.1% of the groins in the standard group and 97.2% of the groins in the fluorescence imaging group (p = 0.33). Groups did not differ in surgical outcome, although more short-term postoperative complications were documented in the standard group (p = 0.041). CONCLUSIONS: Intraoperative visual detection of SLNs in patients with VSCC using ICG-99mTc-nanocolloid was superior compared to 99mTc-nanocolloid and blue dye. The rate of successful SLN procedures between both groups was not significantly different. Fluorescence imaging has potential to be used routinely in the SLN procedure in VSCC patients to facilitate the search by direct visualization. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register (Trial ID NL7443).

Fertility-sparing surgery of cervical cancer >2 cm (International Federation of Gynecology and Obstetrics 2009 stage IB1-IIA) after neoadjuvant chemotherapy.

OBJECTIVE: To assess the feasibility, safety, oncological, and obstetric outcomes in patients with cervical tumors >2 cm treated with neoadjuvant chemotherapy in preparation for abdominal radical trachelectomy. METHODS: A retrospective analysis of patients with cervical cancer >2 cm (up to 6 cm) was conducted in patients who were selected to receive neoadjuvant chemotherapy before abdominal radical trachelectomy. Surgical and clinical outcomes were examined in relation to radiological and pathological results. In addition, obstetric outcomes were described. The Mann-Whitney U test and Fisher's exact test were performed to compare radiological findings between successful and unsuccessful abdominal radical trachelectomy procedures. International Federation of Gynecology and Obstetrics (FIGO) 2009 staging classification was used for this study. RESULTS: A total of 19 women were treated with neoadjuvant chemotherapy for cervical tumors >2 cm at our institution between May 2006 and July 2018. The median age was 28 years (range 19-36). The distribution of FIGO stages was seven patients stage IB1 (37%), 10 patients stage IB2 (53%), and two patients (10%) stage IIA. Mean clinical tumor size was 4.4 cm (range 3.5-6.0). Histology revealed 74% cases of squamous cell carcinoma. The remaining patients had adenocarcinoma (21%) and only one patient had clear cell adenocarcinoma (5%). Chemotherapy consisted of six weekly cycles of cisplatin (70 mg/m2) and paclitaxel (70 mg/m2). In 15 of the 19 patients (74%) fertility was successfully preserved. In the four patients in whom fertility preservation failed, one patient had stable disease after three cycles and did not meet the criteria for fertility-sparing surgery and three patients had intra- or post-operative indications for adjuvant therapy. Three of the 19 patients (15.7%) had a relapse, two of whom died. One case was in the group of successful abdominal radical trachelectomy. CONCLUSION: Neoadjuvant chemotherapy followed by fertility-sparing surgery may be a feasible and safe option in select patients with cervical tumors >2 cm. Unfavorable prognostic factors are defined as non-responsiveness and non-squamous pathology, which can help in patient selection for fertility-sparing surgery.

Efficacy and toxicity of chemoradiation with image-guided adaptive brachytherapy for locally advanced cervical cancer.

OBJECTIVE: To evaluate the efficacy and toxicity of primary chemoradiation with image-guided adaptive brachytherapy for locally advanced cervical cancer and to identify predictors of treatment failure and toxicity. METHODS: Retrospective analysis of 155 stage IB-IVA cervical cancer patients treated from 2008 to 2016 with chemoradiation and image-guided adaptive brachytherapy. Treatment consisted of external beam radiotherapy (45 - 48.6 Gy in 1.8 - 2 Gy fractions) with concurrent weekly cisplatin (40 mg/m2, 5 - 6 cycles) and image-guided adaptive brachytherapy (3-4 × 7 Gy high dose rate) using intracavitary or combined intracavitary-interstitial techniques according to GEC-ESTRO (Group Européen de Curiethérapie and the European Society for Radiotherapy and Oncology) recommendations. Incidences of all outcomes were calculated using Kaplan-Meier's methodology. Risk factors for treatment failure and toxicity were identified using Cox's proportional hazards model and the Kruskal-Wallis H-test respectively. RESULTS: Median follow-up was 57 months. Five-year local control was 90.4 %. Five-year para-aortic lymph node metastasis-free and distant metastasis-free survival were 85.3 % and 70.2 % respectively. Tumor size and lymph node metastasis were independent risk factors for treatment failure. Cumulative incidences of severe late bladder, rectal, bowel, and vaginal toxicity were 0.8%, 3.3%, 3.6%, and 1.4% respectively at 5 years of follow-up. Combined intracavitary-interstitial brachytherapy techniques were associated with less vaginal morbidity. CONCLUSIONS: Primary chemoradiation with image-guided adaptive brachytherapy for locally advanced cervical cancer is a highly effective local and loco-regional treatment. However, survival is compromised by the occurrence of distant metastasis. Patients with large tumors and nodal involvement at diagnosis are at increased risk and may benefit from intensified treatment. Severe late gastrointestinal and urogenital toxicity is limited and may be further reduced by increasing conformity, using combined intracavitary-interstitial techniques and lowering doses to organs at risk.

Incidence and groups at risk for unexpected uterine leiomyosarcoma: a Dutch nationwide cohort study.

OBJECTIVE: To estimate the risk of uterine leiomyosarcoma in patients undergoing gynecological surgery and also to identify groups at risk for unrecognized uterine leiomyosarcoma. METHODS: A national cohort study was performed evaluating all uterine leiomyosarcoma (ULMS) diagnosed in The Netherlands between January 2000 and September 2015. Cases were identified and supplied by the nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA). Unexpected and expected ULMS were compared. Approval for this study was granted by the Medical Ethics Committee of all participating hospitals and by the review board of PALGA. RESULTS: 262 original cases were included. The overall incidence of ULMS in our study was 0.25% or 1:400 patients. The incidence of unexpected ULMS was 0.12% or 1:865 patients. Preoperatively, a malignancy was unexpected in 46% of the cases and expected in 54%. Abnormal uterine bleeding constituted most of the symptoms. 90% of women underwent abdominal hysterectomy and/or bilateral salpingo-oophorectomy. CONCLUSIONS: Leiomyosarcoma are rare. Women aged 40-50 years with abnormal uterine bleeding are most at risk for unexpected ULMS. In contrast, this risk is low in postmenopausal women. ULMS were highly uncommon in women aged under 40 years.

Blinded histopathological characterisation of POLE exonuclease domain-mutant endometrial cancers: sheep in wolf's clothing.

AIMS: POLE exonuclease domain mutations identify a subset of endometrial cancer (EC) patients with an excellent prognosis. The use of this biomarker has been suggested to refine adjuvant treatment decisions, but the necessary sequencing is not widely performed and is relatively expensive. Therefore, we aimed to identify histopathological and immunohistochemical characteristics to aid in the detection of POLE-mutant ECs. METHODS AND RESULTS: Fifty-one POLE-mutant endometrioid, 67 POLE-wild-type endometrioid and 15 POLE-wild-type serous ECs were included (total N = 133). An expert gynaecopathologist, blinded to molecular features, evaluated each case (two or more slides) for 16 morphological characteristics. Immunohistochemistry was performed for p53, p16, MLH1, MSH2, MSH6, and PMS2. POLE-mutant ECs were characterised by a prominent immune infiltrate: 80% showed peritumoral lymphocytes and 59% showed tumour-infiltrating lymphocytes, as compared with 43% and 28% of POLE-wild-type endometrioid ECs, and 27% and 13% of their serous counterparts (P < 0.01, all comparisons). Of POLE-mutant ECs, 33% contained tumour giant cells; this proportion was significantly higher than that in POLE-wild-type endometrioid ECs (10%; P = 0.003), but not significantly different from that in serous ECs (53%). Serous-like features were as often (focally) present in POLE-mutant as in POLE-wild-type endometrioid ECs (6-24%, depending on the feature). The majority of POLE-mutant ECs showed wild-type p53 (86%), negative/focal p16 (82%) and normal mismatch repair protein expression (90%). CONCLUSIONS: A simple combination of morphological and immunohistochemical characteristics (tumour type, grade, peritumoral lymphocytes, MLH1, and p53 expression) can assist in prescreening for POLE exonuclease domain mutations in EC, increasing the probability of a mutation being detected from 7% to 33%. This facilitates the use of this important prognostic biomarker in routine pathology.

Independent validation of the prognostic significance of invasion patterns in endocervical adenocarcinoma: Pattern A predicts excellent survival.

OBJECTIVE: Recently, the pattern of invasion in usual-type human papillomavirus-associated endocervical adenocarcinoma (AC) was put forward as a novel variable to select patients with favourable prognosis. Based on destructiveness of stromal invasion, three patterns were proposed: A - no destructive stromal invasion, B - focal destructive stromal invasion, and C - diffuse destructive stromal invasion. We aimed to independently validate the clinical significance of this classification-system in 82 AC patients, and explored associations between invasion pattern and somatic mutations. METHODS: All patients surgically treated for FIGO stage IB-IIA usual type AC (1990-2011, n = 82) were retrospectively reviewed and classified into pattern A, B or C. Additional immunohistochemical analyses were performed for p53, MSH6, and PMS2. Moreover, previously obtained data on somatic hotspot mutations in 13 relevant genes was integrated. RESULTS: Of 82 AC, 22% showed pattern A, 37% pattern B, and 41% pattern C. Significant differences were observed between invasion patterns and tumour size, depth of invasion (DOI), lymph-vascular invasion (LVI), and lymph-node metastasis. Significantly fewer mutations were present in tumours with pattern A morphology (p = 0.036). All pattern A patients survived (p = 0.002) without recurrent disease (p = 0.005). In multivariate regression analysis including tumour size, DOI, LVI, and lymph node metastasis, invasion pattern was a strong independent predictor for recurrence-free and disease-specific survival (HR 3.75, 95%CI 1.16-12.11, and HR 5.08, 95%CI 1.23-20.98, respectively). CONCLUSIONS: We have independently validated the clinical significance of invasion patterns for usual type endocervical AC. Pattern A predicts excellent survival, and a clinical trial should prove safety of a more conservative treatment for these patients.

Towards spill-free in-bag morcellation: a health failure mode and effects analysis.

BACKGROUND: To assess potential risks of new surgical procedures and devices before their introduction into daily practice, a prospective risk inventory (PRI) is a required step. This study assesses the applicability of the Health Failure Mode and Effects Analysis (HFMEA) as part of a PRI of new technology in minimally invasive gynecologic surgery. METHODS: A reference case was defined of a patient with presumed benign leiomyoma undergoing a laparoscopic hysterectomy or myomectomy including in-bag power morcellation; however, pathology defined a stage I uterine leiomyosarcoma. Using in-bag morcellation as a template, a HFMEA was performed. All steps of the in-bag morcellation technique were identified. Next, the possible hazards of these steps were explored and possible measures to control these hazards were discussed. RESULTS: Five main steps of the morcellation process were identified. For retrieval bags without openings to accommodate instruments inside the bag, 120 risks were identified. Of these risks, 67 should be eliminated. For containment bags with openings 131 risks were identified of which 68 should be eliminated. Of the 10 causes most at risk to cause spillage, two can be eliminated by using appropriate bag materials. Myomectomy appears to be more at risk for residual tissue spillage compared to total hysterectomy. CONCLUSION: The HFMEA has provided important new insights regarding potential weaknesses of the in-bag morcellation technique, particularly with respect to hazardous steps in the morcellation process as well as requirements that bags should meet. As such, this study has shown HFMEA to be a valuable method that identifies and quantifies potential hazards of new technology.

A Controlled Study on Vaginal Blood Flow During Sexual Arousal Among Early-Stage Cervical Cancer Survivors Treated With Conventional Radical or Nerve-Sparing Surgery With or Without Radiotherapy.

OBJECTIVE: Sexual problems among cervical cancer survivors may in part be caused by reduced vaginal blood flow due to damaged hypogastric nerves during radical hysterectomy with pelvic lymphadenectomy and/or by radiation-induced vaginal changes after pelvic radiotherapy. A nerve-sparing modification of radical hysterectomy (NSRH) may preserve vaginal blood flow. Vaginal blood flow during sexual arousal was compared between different treatment modalities. METHODS: We investigated premenopausal women treated for early-stage cervical cancer with radical hysterectomy (n = 29), NSRH (n = 28), NSRH with radiotherapy (n = 14), and controls (n = 31). Genital arousal and subjective sexual arousal in response to sexual stimuli were measured using vaginal photoplethysmography and a questionnaire. Results were compared by using a between-study (treatment groups) by within-study (stimulus) design. RESULTS: Participants were aged 29 to 51 years (mean, 42 years) and at 1 to 14 years (mean, 5 years) after treatment. Measured vaginal blood flow in women treated with NSRH was similar to controls. Women treated with radical hysterectomy had a significantly lower vaginal blood flow compared with controls overall and lower compared with the NSRH group during sexual stimulation. Women treated with radiotherapy had a vaginal blood flow intermediate between the other groups without significant differences. The erotic films were equally effective in enhancing subjective sexual arousal among treatment groups. CONCLUSIONS: Cervical cancer treatment with radical hysterectomy disrupts the vaginal blood flow response, and this may be prevented by conducting an NSRH. Treatment with radiotherapy did not significantly impact vaginal blood flow, but further investigation is needed with a larger sample.

Long-Term Oncological Outcome After Conventional Radical Hysterectomy Versus 2 Nerve-Sparing Modalities for Early Stage Cervical Cancer.

OBJECTIVES: Nerve-sparing radical hysterectomy for early stage cervical cancer was introduced to improve quality of life after treatment. Sparing the pelvic autonomic nerves reduces bladder, bowel, and sexual dysfunction. The Leiden nerve-sparing radical hysterectomy (LNSRH) was modified to the Swift procedure, the latter being more radical regarding the sacrouterine and parametrial resection. We investigate whether nerve-sparing surgery has comparable oncological outcomes as the conventional radical hysterectomy (CRH). Concurrently, we investigate whether there is a difference regarding the oncological outcomes of the 2 nerve-sparing techniques. METHODS: This is a single-center, observational prospective cohort study analyzing oncological outcomes in women undergoing CRH (1994-1999), LNSRH (2001-2005), or Swift procedure (2006-2010) for early stage cervical cancer (International Federation of Gynecology and Obstetrics IA2-IIA). RESULTS: Three hundred sixty-three patients (124 CRH, 122 LNSRH, and 117 Swift) were included. International Federation of Gynecology and Obstetrics stage IB2 or higher (P = 0.005) was significantly more prevalent in the CRH cohort. The 5-year pelvic relapse-free survival and overall survival were not significantly different between the 3 cohorts (P = 0.116). Regarding the nerve-sparing cohorts, the Swift cohort showed a significant better 5-year overall survival (87.2%) compared with the LNSRH cohort (78.8%) (P = 0.04). In the LNSRH cohort, resection planes less than 5 mm free and need for adjuvant therapy were significantly higher than in the Swift cohort (P = 0.026 and 0.046, respectively). CONCLUSIONS: The nerve-sparing radical hysterectomy shows a similar oncological outcome compared with the CRH. The more radical Swift version of nerve-sparing techniques is preferable to the former LNSRH procedure.

Exploring Morphologic and Molecular Aspects of Endometrial Cancer Under Progesterone Treatment in the Context of Fertility Preservation.

OBJECTIVE: The standard treatment of early-stage (FIGO [International Federation of Gynecology and Obstetrics] I) endometrioid endometrial cancer (EEC) is hysterectomy with bilateral salpingo-oophorectomy. An alternative approach for younger women with low-grade EEC who wish to preserve fertility may be hormonal treatment. Previous studies have suggested that progesterone may elicit its antitumor effect in EEC by interacting with the Wingless (Wnt) and/or phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Therefore, we explored whether common activating genetic alterations in Wnt and PI3K/Akt signaling correlated with nonresponsiveness to progesterone therapy for low-grade EEC. In addition, we investigated whether benign morphology under progesterone treatment is accompanied by the absence of genetic changes. METHODS: We analyzed molecular alterations in the Wnt and PI3K/Akt signaling in 84 serial endometrial samples from 11 premenopausal patients with progesterone receptor-positive low-grade EEC conservatively treated with progesterone and correlated these with histological and clinical follow-up. RESULTS: There were 6 responders and 5 nonresponders to progesterone treatment. The response rate to progesterone treatment was 55%, and the relapse rate was 83%. All responders had alterations in both the Wnt and PI3K/Akt pathway before treatment. In the nonresponder group, tumors inconsistently showed alterations in none, 1, or both pathways. Normalization of the endometrium morphology under progesterone treatment is accompanied by the absence of the genetic changes found in the specimen before treatment. CONCLUSIONS: We found that activating molecular alterations in either Wnt or PI3K/Akt signaling pathways did not predict resistance to progesterone treatment. It seems that morphological response goes along with disappearance of the established mutations. This exploratory study suggests that Wnt or PI3K/Akt status is unable to predict response to progesterone treatment in patients with EEC.

Sexual issues among cervical cancer survivors: how can we help women seek help?

OBJECTIVE: Many women treated for cervical cancer (CC) report sexual complaints and sexual distress. It is important to assess these women's and their partners' sexual healthcare needs. This study aims to (a) investigate the prevalence of psychosexual healthcare needs and help-seeking behaviour among CC survivors, (b) identify the association between psychosocial variables and help-seeking intentions among CC survivors and (c) assess survivors' and partners' preferences regarding psychosexual healthcare services. METHODS: A multicentre cross-sectional questionnaire study was conducted in a cohort of women with a history of CC (n=343, mean age=48.7), and their partners (n=154, mean age=50.8). Questions concerned professional healthcare needs, help-seeking behaviour, help-seeking intentions and preferences regarding sexual healthcare services. Furthermore, the questionnaire assessed social cognitive variables related to help-seeking intentions. Data were analysed with multivariate linear regression analyses with future help-seeking intention as an outcome variable. RESULTS: About 51% of the women reported a need for information and/or professional help, although only 35% of these women had initiated a conversation with a professional about sexuality. Women considering sexual functioning important, expecting relief from seeking help, perceiving social support to seek help and having positive beliefs about the quality of professional psychosexual support had higher help-seeking intentions. Women who were embarrassed to discuss sexual issues with a professional were less likely to seek help. Most participants would appreciate receiving information about sexuality and CC. CONCLUSIONS: Many CC survivors have psychosexual healthcare needs, although few seek professional help. Women and their partners should be facilitated in accessing sexual healthcare services.

Sexual rehabilitation after pelvic radiotherapy and vaginal dilator use: consensus using the Delphi method.

OBJECTIVE: This study aimed to reach consensus among professional experts on patient information provision and support regarding sexual rehabilitation and vaginal dilator use after radiotherapy (RT) for gynecological cancers. METHODS: A 3-round online Delphi study was conducted among 10 radiation oncologists, 10 gynecologic oncologists, and 10 oncology nurses from 12 gynecological cancer centers providing RT for gynecological tumors. We assessed the desired content and provider of instructions and patient support regarding sexuality and vaginal dilator use. Responses were measured on a 7-point scale varying from "totally disagree" to "totally agree." Consensus was reached when 70% of participants' answers fell within 2 scale categories with an interquartile range less than or equal to 1. RESULTS: The panel agreed that information about sexual rehabilitation using vaginal dilators should be provided by radiation oncologists before treatment. Information should always be provided to sexually active cervical and vaginal cancer patients younger than 70 years. Tailored information was recommended for vulvar and endometrial cancer patients, patients older than 70 years, and sexually inactive patients. Preferably, specifically trained oncology nurses should give psychological and practical support. Participants recommended vaginal dilation to prevent vaginal adhesions, tightening, and shortening. The panel advised to start dilation around 4 weeks after treatment to perform dilation 2 to 3 times a week for 1 to 3 minutes and to continue dilation for 9 to 12 months. Plastic dilator sets were considered the most suitable type of dilator. CONCLUSIONS: Consensus was reached on patient information provision and support during sexual rehabilitation after RT for gynecological cancers. Results were used to develop a sexual rehabilitation intervention.

Nerve-sparing radical abdominal trachelectomy versus nerve-sparing radical hysterectomy in early-stage (FIGO IA2-IB) cervical cancer: a comparative study on feasibility and outcome.

OBJECTIVES: Standard treatment in early-stage cervical cancer is a radical hysterectomy (RH) with pelvic lymphadenectomy. In women who wish to preserve fertility radical vaginal trachelectomy has been proposed; however, this is not feasible in larger tumors, and nerve-sparing surgery is not possible. Nerve-sparing radical abdominal trachelectomy (NSRAT) overcomes these disadvantages. METHODS: Case-control study of women with early-stage cervical cancer (International Federation of Gynecology and Obstetrics IA2-IB) submitted to NSRAT from 2000 until 2011. Women submitted to nerve-sparing RH with early-stage cervical cancer were included as control subjects. RESULTS: Twenty-eight patients and 77 control subjects were included. Neoadjuvant chemotherapy was administered in 3 women before NSRAT because the linear extension was or exceeded 40 mm. Local recurrence rate was 3.6% (95% confidence interval [CI], 0.00-10.6) in the NSRAT group compared with 7.8% (95% CI, 1.7-13.9) in the control group (P = 0.44). No significant difference was found between both groups regarding disease-free survival and survival. The overall pregnancy rate was 52.9% (95% CI, 28.7%-77.2%). The mean follow-up was 47.3 months (range, 6-122 months) for NSRAT and 51.8 months (11-129.6 months) for nerve-sparing RH. CONCLUSIONS: Nerve-sparing radical abdominal trachelectomy seems safe and effective in women with early-stage cervical cancer who wish to preserve fertility. Respective women should be informed about this treatment option, especially if the tumor is too large for radical vaginal trachelectomy.

Prediction of recurrence risk in endometrial cancer with multimodal deep learning.

Predicting distant recurrence of endometrial cancer (EC) is crucial for personalized adjuvant treatment. The current gold standard of combined pathological and molecular profiling is costly, hampering implementation. Here we developed HECTOR (histopathology-based endometrial cancer tailored outcome risk), a multimodal deep learning prognostic model using hematoxylin and eosin-stained, whole-slide images and tumor stage as input, on 2,072 patients from eight EC cohorts including the PORTEC-1/-2/-3 randomized trials. HECTOR demonstrated C-indices in internal (n = 353) and two external (n = 160 and n = 151) test sets of 0.789, 0.828 and 0.815, respectively, outperforming the current gold standard, and identified patients with markedly different outcomes (10-year distant recurrence-free probabilities of 97.0%, 77.7% and 58.1% for HECTOR low-, intermediate- and high-risk groups, respectively, by Kaplan-Meier analysis). HECTOR also predicted adjuvant chemotherapy benefit better than current methods. Morphological and genomic feature extraction identified correlates of HECTOR risk groups, some with therapeutic potential. HECTOR improves on the current gold standard and may help delivery of personalized treatment in EC.

Self-reported sexual, bowel and bladder function in cervical cancer patients following different treatment modalities: longitudinal prospective cohort study.

OBJECTIVE: Conventional radical hysterectomy with pelvic lymphadenectomy (RHL) for early-stage cervical cancer is associated with significant bladder, anorectal, and sexual dysfunction. Nerve-sparing modification of RHL (NS-RHL) has been developed with the aim to reduce surgical treatment-related morbidity. Postoperative radiation therapy (RT) is offered to patients with unfavorable prognostic features to improve local control. The aim of the study was to assess self-reported morbidity of various types of treatment in cervical cancer patients. METHODS: Self-reported symptoms were prospectively assessed before and 1 and 2 years after treatment by the Dutch Gynaecologic Leiden Questionnaire. RESULTS: Included were 229 women (123 NS-RHL and 106 conventional RHL). Ninety-four (41%) received RT. Up to 2 years (response rate, 81%), women reported significantly more bowel, bladder, and sexual symptoms compared with the pretreatment situation. No significant difference was found between the conventional RHL and NS-RHL with the exception of the unexpected finding that a smaller percentage in the NS-RHL group (34% vs 68%) complained about numbness of the labia and/ or thigh. Radiation therapy had a negative impact on diarrhea, urine incontinence, lymphedema, and sexual symptoms (especially a narrow/short vagina). CONCLUSIONS: In the current longitudinal cohort study, treatment for early-stage cervical cancer was associated with worse subjective bladder, anorectal, and sexual functioning, irrespective of the surgical procedure used. Postoperative RT resulted in a significant deterioration of these functions. The results have to be interpreted with caution in view of the study design and method used.

Guideline-Based Algorithmic Recommendations Versus Multidisciplinary Team Advice for Gynecologic Oncology.

Evidence-based clinical decision making in oncology is challenging. Multi-disciplinary team (MDTs) meetings are organized to consider different diagnostic and treatment options. MDT advice are often based on clinical practice guideline recommendations which can be extensive and ambiguous, making it difficult to implement in clinical practice. To address this issue, guideline-based algorithms have been developed. These are applicable in clinical practice and enable accurate guideline adherence evaluation. This ongoing study aims to determine the optimal decision-making approach for different subpopulations of patients with high-incidence gynecological cancers.

Incidence of gynaecological cancer during the COVID-19 pandemic: A population-based study in the Netherlands.

OBJECTIVE: To study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands. METHODS: We performed a retrospective cohort study using data from the Netherlands Cancer Registry (NCR) on women of 18 years and older diagnosed with invasive endometrial, ovarian, cervical or vulvar cancer in the period 2017-2021. Analyses were stratified for age, socioeconomical status (SES) and region. RESULTS: The incidence rate of gynaecological cancer was 67/100.000 (n = 4832) before (2017-2019) and 68/100.000 (n = 4833) during (2020) the COVID-19 pandemic. Comparing the number of diagnoses of the two periods for the four types of cancer separately showed no significant difference. During the first wave of COVID-19 (March-June 2020), a clear decrease in number of gynaecological cancer diagnoses was visible (20-34 %). Subsequently, large increases in number of diagnoses were visible (11-29 %). No significant differences in incidence were found between different age groups, SES and regions. In 2021 an increase of 5.9 % in number of diagnoses was seen. CONCLUSION: In the Netherlands, a clear drop in number of diagnoses was visible for all four types of gynaecological cancers during the first wave, with a subsequent increase in number of diagnoses in the second part of 2020 and in 2021. No differences between SES groups were found. This illustrates good organisation of and access to health care in the Netherlands.